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CLINICAL PRACTICE GUIDELINES

Clinical Practice Guidelines for Management of Bipolar Disorder

Nilesh Shah, Sandeep Grover1, G. Prasad Rao2
Department of Psychiatry, L. T. M. Medical College and General Hospital, Sion, Mumbai, 1Department of Psychiatry,
Post Graduate Institute of Medical Education and Research, Chandigarh, 2Schizophrenia and Psychopharmacology Division,
Asha Hospital., Banjara Hills, Hyderabad, India

shown to have subthreshold BPAD with a range of 0.1 to 2.4%

Participants of expert group on CPG for Bipolar Affective
with a mean of 1.4 (SD-0.8). There is no nationwide study to
Disorder
evaluate the prevalence rates of BPAD in India. In a country
like India, patients have limited resources, poor knowledge
Vidhyadhar Watve, Mrugesh Vaishnav, Vivek Kirpekar,
about the disorder and treatment; have inadequate access
D.K. Sharma, Mahendra Jain, Asim Kumar Mallick,
to the health care facilities, which makes treatment of
C.L. Narayan, Anup Bharti, Madhu Nijhawan.
BPAD a challenge. Indian Psychiatric Society (IPS) made first
attempt to formulate Clinical Practice Guidelines (CPGs) for
INTRODUCTION
management of BPAD in 2005. Since then, over the last one
decade there have been several developments, especially in
Bipolar disorder (BPAD) is a serious mental disorder
the form of emergence of new evidence for some of the
characterized by episodes of depression, hypomania/mania
pharmacological agents. Accordingly, these new guidelines
and mixed episodes, with interepisodic recovery. However,
attempt to update the previous guidelines published by
many patients with BPAD continue to exhibit residual
IPS. These guidelines should be read along with the earlier
symptoms in the interepisodic period. The illness usually
version of the CPGs, published by IPS in 2005.
starts in adolescence or early adulthood and has significant
negative impact on the life of the sufferer and their caregivers.
ASSESSMENT AND EVALUATION [TABLE-1]
Patients with BPAD encounter educational difficulties, job
related problems, interpersonal difficulties, psychosocial
Assessment of patients is an ongoing process and
dysfunction, disability, marital problems, multiple suicidal
comprehensive assessment of a patient involves the
attempts, completed suicide and medication side effects.
assessment of patients themselves and their caregivers.
Additionally patients with BPAD have high rates of physical
The role of taking a proper history from the patient and
and psychiatric comorbidity. The prevalence rates of BPAD
all the available resources cannot be over-emphasized. In
vary from country to country. A large multinational study
addition to the history taking, proper attention must be
suggests that lifetime prevalence of BPAD-I ranges from
paid to the mental status examination. Diagnosis of BPAD
0-1% with a mean of 0.6 (SD-0.4). The prevalence rate of
is to be made on the basis of current diagnostic criteria,
BPAD-II ranges from 0 to 1.1% with a mean of 0.4 (SD-0.3).
because a diagnosis based on diagnostic criteria can be
Additionally a significant proportion of patients have been
considered more reliable, facilitates communication among
various clinicians and paves the way for management on the
basis of evidence based recommendations. It is important
Address for correspondence:
Dr. Nilesh Shah, Department of Psychiatry, L. T. M. Medical to remember that especially during the initial part of the
College and General Hospital, Sion, Mumbai - 400 022, illness, the symptoms may be confusing and at times it
Maharastra, India. may be difficult to distinguish symptoms of mania from
E-mail: drnilshah@hotmail.com,
other psychiatric syndromes like schizophrenia, acute
Dr. Sandeep Grover, Additional Professor, Department of
Psychiatry, PGIMER, Chandigarh, India.
E-mail: drsandeepg2002@yahoo.com
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DOI:
How to cite this article: Shah N, Grover S, Rao GP. Clinical
Practice Guidelines for Management of Bipolar Disorder.
10.4103/0019-5545.196974
Indian J Psychiatry 2017;59:51-66.

© 2017 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow S51

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Shah, et al.: CPGs for bipolar disorders
Table 1: Components of assessment and evaluation
Basic assessments
• Comprehensive assessment of both patients and caregivers
• Complete history with information from all possible sources in terms of
type of first episode in lifetime, predominant polarity of illness, duration
and severity of episodes, inter‑episodic recovery, presence or absence of
suicidal behaviour, violence and agitation, seasonal variation in onset of
symptoms, presence of rapid cycling and ultra‑rapid cycling features
• History taking focusing on precipitating factors‑ psychosocial stressors,
disturbances in biological rhythms
• Physical examination‑ record data such as blood pressure, weight and
wherever indicated body mass index and waist circumference
• Mental state examination
• Establish diagnosis according to current diagnostic criteria
• Differential diagnosis by ruling out secondary affective disorder
• Proper assessment of the current polarity of the illness
• Evaluate the risk for suicidal behaviour‑ suicidal ideations, intent, plans;
access to means for suicide, possible lethality in case patient uses the
means, psychotic symptoms in the form of commanding hallucinations,
severe anxiety, comorbid substance use, past history of suicidal
attempts and non‑suicidal self‑harming, family history of self‑harm and
completed suicide
• Areas to be evaluated during the current episode: symptom‑severity,
symptom‑dimensions, comorbid physical and psychiatric including
substance use conditions, risk of harm to self and others, level of
functioning and socio‑cultural milieu of the patient
• Past treatment history: type of medications used, response to treatment,
duration of use of treatment, side effects experienced and reasons for
discontinuation
• Basic investigations: haemogram, blood sugar and lipid levels, liver
functions, renal functions, electrocardiogram
• Assessments of caregivers: knowledge about illness, knowledge about
treatment, their attitudes and beliefs regarding treatment, the impact of
the illness on them and their personal and social resources in the form of
burden, distress, stigma, personal and marital life
• Ongoing assessments: response to treatment, side effects, treatment
adherence, issues of marriage and pregnancy, disability, other health‑care
needs, ease of access to treatment team, therapeutic alliance, etc.
Additional/Optional assessments
• Use of standardized rating scales to rate various aspects of the illness
• Psychological testing for cognitive functions
• Neuroimaging especially in those with atypical features, neurological
signs, non‑response to treatment, later age of onset and elderly patients
and transient psychosis and other psychiatric disorders.
A possibility of substance induced disorder or disorder
secondary to organic causes is to be considered, when
the symptoms are atypical or there is evidence of the use
of substance or underlying organic causes. Occasionally
establishing the definite diagnosis of BPAD may require
time.
The assessment may cover history of number of previous
episodes, type of first episode in lifetime, predominant
polarity of illness, duration and severity of episodes,
inter-episodic recovery, presence or absence of suicidal
behaviour, violence and agitation, seasonal variation in
onset of symptoms, presence of rapid cycling and features of
ultra-rapid cycling. Assessment of current episode may also
focus on the issues of severity of symptoms, suicidality and
agitation. Understanding the role of various psychosocial
S52
stressors and biological rhythms in onset of illness,
precipitation of relapse and continuation of symptoms need
to be understood thoroughly.
A thorough assessment includes assessment of comorbid
psychiatric and medical conditions. It is important to
remember that many a times; comorbidity is not very evident
during the acute episode of illness. The comorbid conditions
become more evident when the patient has come out of the
acute episode of the illness. Evaluation of comorbid substance
abuse needs to consider the type and frequency of substance
abuse. If the patient does not provide adequate information
about the substance use pattern, but there is high index of
suspicion, urine or blood screens (with prior consent) can be
used to confirm the existence of comorbid substance use/
dependence, wherever such facilities are available. Functional
impairment in various domains of life including impact of the
illness on the family functioning and psychosocial impact of
the illness on the caregivers is not to be neglected. A thorough
physical examination need to be done to rule out presence of
any physical illness and also to rule out episodes secondary
to physical illnesses. This may be supplemented by the
judicious use of investigations. Depending on the feasibility,
unstructured clinical assessments need to be supplemented
by documentation of severity and extent of symptoms on
appropriate standardized rating scales. Patients with bipolar
disorders also have cognitive deficits. Accordingly, depending
on the need, detailed cognitive testing may be undertaken.
The use of neuroimaging may be indicated in those with
atypical features, neurological signs, non-response to
treatment and having first episode of illness at a later age
and elderly. Caregiver’s assessment may involve evaluation of
their knowledge about illness, knowledge about treatment,
their attitudes and beliefs regarding treatment, the impact of
the illness on them and their personal and social resources
in the form of burden, distress, stigma, personal and marital
life etc.
In case patient has received treatment in the past, then it is
important to record the type of medications used, response
to treatment, duration of use of treatment, side effects
experienced and reasons for discontinuation.
Importance of ongoing assessment cannot be
underestimated. With progress in treatment, new issues like
response to treatment, side effects, treatment adherence,
marriage, pregnancy, disability, other health-care needs,
ease of access to treatment team and therapeutic alliance
may need to be assessed from time to time.
FORMULATING A TREATMENT PLAN [FIGURE 1]
Formulation of treatment plan will involve decision making
about the treatment setting, treatments to be used and areas
to be addressed. Treatment plan need to be formulated in
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Shah, et al.: CPGs for bipolar disorders

Patient with Affective Symptoms

Consider differential diagnoses like

• Organic Mental Conditions
• Substance induced disorder
• Acute and transient psychotic disorder
• Other psychotic disorders

Establish the diagnosis of BPAD

Assessment
• Severity of Current episode
• Risk of harm to self and others
• Comorbid substance use/dependence
• Level of functioning
• Detailed Physical examination
• Record- blood pressure, weight and wherever indicated body mass index and waist
circumference
• Mental Status Examination
• Investigations- haemogram, liver function test, renal function test, fasting blood glucose
level, electrocardiogram
• Treatment history- response to previous medication trials, compliance, side effects, etc.
• Patient’s and caregivers beliefs about the cause of illness and beliefs about the treatment
• Assessment for social support, stigma, coping
• Assessment of caregiver burden, coping and distress

• Decide about treatment setting- consider inpatient care in case of suicidality, severe agitation
and violence, malnutrition, catatonia, patient unable to care for self to the extent that she/he
requires constant supervision or support, comorbid general medical conditions making
management difficult at the outpatient setting
• Liaison with other specialists depending on the need of the patient

Electroconvulsive therapy Non-Pharmacological

Pharmacological Management
• Catatonia, rapid control Management
• Choose an agent based on the current
of symptoms, suicidality, • Psychoeducation
polarity, presence or absence of psychotic
past response to ECT, • Psychosocial
symptoms in the current episode, past
augmentation etc. intervention
treatment response, past history of side
effects, cost, comorbidity, patient/family
preference, preferred route of
administration, availability of medications,
current metabolic profile, past history of
compliance, treatment resistance

Figure 1: Initial evaluation and management plan for schizophrenia

consultation with patients, caregivers and other members
involved in the treatment team. Treatment plans may be
guided by the needs and be practical, feasible and flexible.
Further, the treatment plan is be re-evaluated from time to
time and be modified as per the needs.
CHOICE OF TREATMENT SETTINGS
In general, most of the patients with BPAD are managed
on the outpatient setting. However, some patients may
require inpatient care. Whenever possible patient admitted
to the inpatient setting should have accompanying family
caregivers. In case inpatient care is required and such
facilities are not available, than the patient and/or family
need to be informed about the need for inpatient care and
patient may be referred to the nearest available inpatient
facility and admission may be facilitated.
OPTIONS FOR MANAGEMENT OF BIPOLAR
DISORDER
Treatment options for management of BPAD can be broadly
classified as mood stabilizers, antidepressants, antipsychotic
medications, electroconvulsive therapy (ECT), adjunctive
medications and psychosocial interventions [Table-2]. Use of
various treatment options is guided by the phase of illness
(mania/hypomania/depression/mixed) in which patient
presents to the clinician and past treatment history.
PHARMACOLOGICAL MANAGEMENT OF
BIPOLAR DISORDER
The mainstay of management of BPAD is mood stabilizers.
The available mood stabilizers include lithium, valproate,
lamotrigine, carbamazepine/oxcarbazepine and topiramate.

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Shah, et al.: CPGs for bipolar disorders
Lithium
Lithium is the oldest mood stabilizer used in the management
of BPAD. It has been found to be efficacious in management
of acute episode of either polarity and has been found to
be efficacious in prevention or relapse of episodes of either
polarity. Additionally, it has been shown to have a role in
prevention of suicide in patients with BPAD.
Prior to starting lithium, history need to be reviewed for
the presence of physical illnesses like renal dysfunction,
thyroid dysfunction and cardiac conduction abnormalities.
Additionally information needs to be reviewed for
presence of dermatological diseases. In case of women,
last menstrual period is to be ascertained and if required
urine pregnancy test need to be done. Further, prior to
starting lithium, patients need to be educated about the
various side effects of lithium, use of salt-restricted diet and
avoidance of medications (diuretics, angiotensin-converting
enzyme inhibitors, non-steroidal anti-inflammatory drugs,
cyclooxygenase-2 inhibitors, etc.) which can increase
serum lithium levels. Patients also need to be informed to
avoid dehydration. Whenever lithium is started, it need to
be started in low doses, preferably in divided doses and
the dose need to be titrated upwards with monitoring
of serum lithium levels. As steady state levels of lithium
are achieved after about 5 days of starting lithium or dose
increment, the levels are be done after 5 days of start of
treatment or change in the dose. However, the levels may
be checked earlier if patient manifests features of toxicity.
The serum levels of lithium, which are usually required for
management of acute episode, are in the range of 0.6 to 1.0
Table 2: Options for management for Bipolar disorder
Mood Stabilisers
• Lithium
• Divalproex/valproate
• Carbamazepine/Oxcarbazepine
• Lamotrigine
• Topiramate
• Gabapentin
Antidepressants
• Tricyclics, Selective serotonin reuptake inhibitors, Serotonin and
nor‑epinephrine reuptake inhibitors, bupropion, mirtazapine, etc.
Antipsychotic medications
• First‑generation antipsychotic medications (Oral/parenteral/depot or
long acting‑ preparations)
• Second‑generation antipsychotic medications (Oral/parenteral/depot or
long acting‑ preparations)
Somatic treatments
• Electroconvulsive therapy (ECT), transcranial magnetic
stimulation (rTMS), transcranial direct current stimulation (tDCS)
Adjunctive medications
• Anticholinergics, antidepressants, benzodiazepines, hypnotic‑sedatives,
anticonvulsants, lithium carbonate
Psychosocial interventions
• Social rhythm therapy, cognitive behavioural therapy, family
intervention, cognitive remediation, individual therapy, group therapy,
social skills training, vocational rehabilitation
Other measures
• Lifestyle and dietary modifications
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meq/litre and for prophylaxis range from 0.6 to 0.8 meq/
litre; however, few studies suggest that serum levels as low
as 0.4 to 0.8 meq/litre may be sufficient for prophylaxis,
albeit are associated with higher risk of relapse. Once the
dose is stabilized, patient may be shifted to once a day
dose to reduce the side effects and improve the medication
compliance. Serum lithium levels may be monitored every
3-4 months. Renal function tests need to be monitored
once in every 2-3 months during the initial 6 months of
therapy and thyroid function tests need to be monitored
once or twice during the first 6 months of treatment.
Later, renal and thyroid function tests may be monitored
once in 6 months to 1 year in clinically stable patients
and more frequently if so indicated (see table-3). Lithium
is usually preferred in patients who have classical mania,
bipolar depression, predominant polarity of illness is that
of depression, episodic course of illness, manic-depressive-
euthymic course, non-rapid cycling course of illness, lack
of mixed episode, older age of onset for BPAD, presence
of family history of BPAD and presence of family history of
lithium response.
Divalproex/valproate
Divalproex and its formulations (sodium valproate
and valproic acid) have been found to be useful in the
management of BPAD. It has been found to be efficacious
Table 3: Investigations prior to starting of lithium and
while monitoring lithium therapy
Pre‑lithium evaluation
• Serum Urea, Creatinine
• Serum electrolytes
• Thyroid function test
• May evaluate serum osmolality
• May evaluate 24 hour urine volume, proteins, creatinine, osmolality
• May calculate the eGFR
• Haemogram
• Urine Pregnancy test (in case of women)
• Electrocardiogram
• Fasting blood sugar
• Lipid Profile
• Anthropometry‑ height, weight, waist circumference
Monitoring of lithium therapy
• During the initial phase of illness, serum lithium levels must be done
after 5 days of a stable dose.
• Sample for serum lithium levels must be taken 12‑14 hours after the last
dose of lithium
• If the medication is being given as BD or TID dose, the morning dose
need to be withheld prior to collection of blood sample for serum
lithium level
Monitoring of side effects: at every visit enquire about polyuria/
polydipsia, gastrointestinal side effects; Check for tremor, dysarthria,
ataxia
Monitoring of serum lithium levels: Once the dose of lithium has been
stabilized the serum levels must be done once in every 3‑4 months; more
frequent monitoring may be done in elderly and those receiving with
concurrent medications like diuretics, and in those with renal impairment
Investigations to be repeated 6‑12 monthly as indicated: 24 hour urine
volume, urinary proteins, serum urea and creatinine, Thyroid function
tests, eGFR, S. Calcium
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in management of acute mania and mixed episodes. The
evidence for its efficacy in acute depression is not as robust
as that for lithium. It is also efficacious in prevention of
mania and depression, when used during the maintenance
phase. As with lithium, prior to starting valproate, clinicians
need to review the medical history for presence of any
hepatic, haematological and bleeding problems. Prior
to starting of valproate, patient is to be educated about
the side effects, especially about signs and symptoms of
hepatic and haematological dysfunction. They need to be
instructed to report to the clinicians at the earliest if these
signs and symptoms emerge. Prior to starting valproate, it
is important to investigate the patient for liver function test
and haemogram. In young women, last menstrual periods
need to be ascertained and if required urine pregnancy test
need to be done to rule out pregnancy. As valproate is
associated with weight gain and metabolic abnormalities, it
may be a good practice to evaluate the lipid profile, fasting
blood glucose levels and anthropometry (Table-4).
Usually valproate is started in low doses, i.e., 250 mg BD or
250 mg TID and titrated upwards with monitoring of side
effects and serum levels. However, some of the studies
have also evaluated rapid titration of valproate dose with
initial dose of 20-30 mg/day and have shown that it is well
tolerated. Maximum daily dose which is recommended is
60 mg/day but most patients do not require such high doses.
The usual therapeutic serum levels which are considered to
be efficacious vary from 50 to 100µg/ml. Once the dose
of valproate is stabilized, the dosing schedule need to be
changed to OD or BD dosing to reduce the side effects and
improve compliance. In case OD dosing is given, extended
release formulation may be used. However, it is important
to remember that the bioavailability of extended release
formulations is about 15% less than the immediate release
preparations and the dose is to be increased accordingly.
Serum valproate levels are to be done after 5 days of starting
or increase in the dose of valproate. The sample need to
be collected after 12 hours in case patient is receiving
immediate release formulation, however, if the patient is
receiving extended release formulation, the sample may be
collected after 21 to 24 hours (table-5). There is evidence
to suggest that patients with BPAD-II, dysphoric or mixed
mania, rapid cycling affective disorder, stable episode
frequency, later age of onset of illness, shorter duration of
illness, long and severe course of illness respond well to
valproate. Other indicators for good response to valproate
include presence of comorbid alcohol use disorder, mental
retardation, anxiety and panic attacks, post-traumatic stress
disorders, marked sleep disturbances, explosive dyscontrol
and aggression and comorbid migraine.
Lamotrigine
The role of lamotrigine in management of BPAD has been
well studied now and it has been shown to be efficacious
in management of bipolar depression and prevention of
Indian J Psychiatry 59 (Supplement 1), January 2017
Table 4: Investigations prior to starting of valproate and
while monitoring valproate therapy
Pre‑valproate evaluation
• Haemogram
• Liver Function Test
• Urine Pregnancy test (in case of women)
• Fasting blood sugar
• Lipid Profile
• Anthropometry
Monitoring of valproate therapy
Routine monitoring of haemogram and liver function test is not
recommended. May be done every 6‑12 monthly in patients receiving
long term valproate therapy
The therapeutic range for serum valproic acid level is 50‑100 µg/mL
Serum valproate levels during initial titration are to be done after 5 days
of a stable dose.
When to collect the sample: sample may be collected after 12 hours in
case patient is receiving immediate release formulation, however, if the
patient is taking extended release formulation, blood sample need to be
collected 21‑24 hours after the last dose to estimate the serum valproate
levels
Table 5: Investigations prior to starting of valproate and
while monitoring valproate therapy
Pre‑Carbamezapine evaluation
• Haemogram
• Liver Function Test
• Urine Pregnancy test (in case of women)
• Renal Function test
• Serum electrolytes (in case of elderly)
• Fasting blood sugar
• Lipid Profile
• Anthropometry
Monitoring of carbamazepine therapy
• Monitoring of haemogram including platelet counts and liver function
test need to be done every 2 weekly during the initial 2 months of
treatment
• After first 2 months: if no abnormalities are noted during the first
2 months, than the Haemogram and liver function tests may be done
every three monthly.
• The therapeutic range for serum carbamazepine level is 4‑12 µg/ml
• Serum carbamazepine levels during initial titration are to be done after
5 days of a stable dose.
When to collect the sample: sample may be collected after 12 hours of
the last dose
relapse of depression. However, the most dreaded side
effect of lamotrigine includes skin rash, including Stevens
- Johnson syndrome and toxic epidermal necrolysis.
The skin lesions can occur any time during the therapy,
but are more often reported during the initial phase of
treatment and when used along with valproate. Evidence
suggests that the risk of skin rash can be reduced by
slow upward titration of the dose. Accordingly, while
considering lamotrigine, patients need to be informed
about the possibility of rash and told to contact the
treating psychiatrist in case rash is seen. When the rash
is more widespread, diffuse and associated with systemic
symptoms like fever or sore throat, lamotrigine may be
stopped. When initiated, lamotrigine may be started at
the dose of 25 mg/day for initial 2 weeks, then it may be
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Shah, et al.: CPGs for bipolar disorders
given at the dose of 50 mg/day during the 3rd and 4th week.
After that 50 mg/day can be increased per week depending
on the therapeutic response.
Carbamazepine
Carbamazepine has been shown to be efficacious in the
management of acute bipolar mania and prevention of
relapse. Prior to starting carbamazepine, clinician needs
to focus on the history of blood dyscrasias and hepatic
dysfunction. When carbamazepine is considered, patients
need to be informed about the signs and symptoms of
hepatic dysfunction, haematological dysfunction and skin
reactions and told to report to the psychiatrist if these
symptoms emerge. Baseline investigation prior to starting
of carbamazepine may include complete haemogram, liver
function tests and renal function test (Table-5). When used
in elderly serum electrolytes may also be done, in view of the
risk of hyponatremia. Usual starting dose of carbamazepine
is 200 mg/day given in divided doses and titrated upward
slowly. Once the dose of 800-1000 mg/day is reached the
increment of dose may be slower and the usual maintenance
dose is about 1000 mg/day, but it can vary from patient to
patient and may be 200 to 1600 mg/day. The carbamazepine
therapeutic drug levels have not been established in patients
with BPAD and the serum levels of 4-12 µg/ml, which is
recommended for seizure disorders is commonly used. As
with lithium and valproate the serum levels need to be done
after 5 days of initiation of treatment or increment of dose.
Other anticonvulsants
There is lack of data in the form of double blind randomized
controlled trials for Oxcarbazepine, but small open label
studies suggests that it may be of some benefit as monotherapy
or add-on therapy in patients with refractory mania. The data
from open label studies suggest the usefulness of add-on
therapy with topiramate in patients with bipolar depression.
Studies which have evaluated the role of gabapentin in
management of mania have yielded negative results.
Antipsychotics
Over the last decade or so, many large multicentric double
blind placebo controlled and active comparator randomised
controlled studies have evaluated the role of various atypical
antipsychotics like olanzapine, quetiapine, aripiprazole,
risperidone, paliperidone, amisulpiride, asenapine,
ziprasidone and haloperidol etc. in the management of
bipolar depression, bipolar mania and for maintenance
phase treatment. Data from these studies suggest that
antipsychotics like olanzapine, quetiapine, aripiprazole,
risperidone, paliperidone and ziprasidone are effective in
the management of acute mania. There is evidence for use
of quetiapine monotherapy, and olanzapine and fluoxetine
combination in the management of bipolar depression.
There is evidence for lurasidone in the management of acute
episode of bipolar depression. Olanzapine and quetiapine
monotherapy or as adjunctive medications to lithium or
S56
valproate have been shown to be efficacious in prevention
of relapse of both depression and mania. Antipsychotics
like long acting risperidone, ziprasidone have been shown
to be beneficial in prevention of mania as monotherapy or
as adjunctive medications to lithium or valproate.
Combination therapy
There is evidence to suggest that when lithium or valproate
is combined with antipsychotics in the management of acute
mania, the efficacy is higher and the onset of action is faster
than that reported for single agent. Accordingly, depending
on the severity of mania, combinations may be used.
Electroconvulsive Therapy (ECT)
There is evidence for use of ECT in the management of acute
mania, mixed episode and bipolar depression. Indications
for use of ECT are shown in Table-6.
Benzodiazepines
Studies have evaluated the efficacy of adds-on
benzodiazepines like clonazepam and lorazepam to lithium
and current level of evidence suggests that the antimanic
properties of these agents are difficult to distinguish from
the sedative properties of these agents. Accordingly, these
agents are considered to be adjunctive agents, which may
be useful in management of acute episode. Further, there is
evidence to suggest the beneficial role of lorazepam in the
management of agitation and catatonia.
Other agents
Many other medications like calcium channel blockers,
zonisamide, levetiracetam, acamprosate, omega-3 fatty
acids, allopurinol etc, have been evaluated in small sample
size trials as monotherapy or add on agents. However,
available the evidence is not sufficient to recommend these
medications as first line agents in management of bipolar
mania and depression.
Antidepressants
Conventionally antidepressants have been used in the
management of bipolar depression. However, over the last 2
decades or so, use of antidepressants in patients with bipolar
Table 6: Possible indications of use of ECT in patients of
schizophrenia
• Bipolar depression not responding to adequate pharmacotherapy
• Bipolar mania not responding to adequate pharmacotherapy
• Catatonic symptoms
• Need for rapid control of symptoms
• Presence of suicidal behaviour which puts the life of the patient at risk
• Presence of severe agitation or violence which puts the life of others at risk
• Refusal to eat which puts the life of patient at risk
• History of good response in the past
• Augmentation of partial response to pharmacotherapy
• Not able to tolerate pharmacotherapy
• Treatment resistant illness
• Episodes of severe depression or mania during pregnancy
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depression has emerged as a controversial topic in view of
the risk of antidepressant-induced manic/hypomanic switch.
Evidence from metanalysis suggests that use of antidepressants
along with mood stabilizers is superior to use of combination
of a mood stabilizer and a placebo and is not associated with
increased risk of manic switch. Most of the studies which
have not found adds-on antidepressants to be beneficial
have involved paroxetine, hence, if one want to avoid use of
an antidepressant, paroxetine is to be avoided. Among the
various antidepressants, bupropion has been reported to be
associated with lowest risk of antidepressant induced switch.
However, it is important to remember that antidepressants
should not be used as monotherapy, and in those with rapid
cycling affective disorder and mixed episodes.
Adequate trial
The minimum recommended duration of treatment to
consider it to be an effective trial for an acute manic episode
is about 3-4 weeks. In case of bipolar depression, a 6 weeks
trial is considered as an adequate trial.
NON-PHARMACOLOGICAL MANAGEMENT OF
BIPOLAR DISORDER
Psychosocial management as an adjunct to pharmacotherapy
has been shown to be of significant benefit during
the management of acute phase of bipolar depression
and maintenance phase of illness. Among the various
psychosocial interventions, data supports the use of
psychoeducation (individual and group), interpersonal and
social rhythm therapy (IPSRT), cognitive behaviour therapy
and family focused intervention. These psychosocial
interventions have been shown to be associated with
reduced risk of relapses, better functioning and better
treatment adherence. The basic components of all these
programs involve informing the patients about their illness,
identifying the early signs of relapse, handling stress,
maintaining social rhythms, addressing the interpersonal
issues and expressed emotions, problem solving and
enhancing medication and treatment adherence.
Psychoeducation for patients and or family (Table 7)
Psychoeducation may be considered both for the patient
and family members (Table 7). The aim is to be to
educate the patient and family about the illness. They
may be provided simple explanations about the nature
of the illness, treatment options, possible side effects of
medications and likely length of treatment etc. Caregivers
may also be provided with an opportunity to vent out their
feelings and distress. Psychoeducation may also address
the important issue of treatment adherence and identifying
early signs of new episode. It is important to remember that
psychoeducation is not a onetime event and prior to every
session, feedback of the previous sessions may be taken
and psychoeducation need to be tailored to the needs of
the patient and the caregivers.
Indian J Psychiatry 59 (Supplement 1), January 2017
Table 7: Basic components of Psychoeducation
• Assessing the knowledge of the patient and caregivers about aetiology,
treatment and prognosis
• Introduction of diagnosis
• Discussing the symptoms of depression, mania, hypomania and mixed
episodes
• Providing information about aetiology
• Dealing with day today stress
• Providing information about the importance of stress management and
regular habits
• Providing information about available treatment options, their efficacy/
effectiveness, side effects, duration of use
• Discussing about importance of medication and treatment compliance
• Providing information about possible course and long term outcome
• Discussing about problems of substance abuse, marriage and other issues
• How to detect early signs of relapse
• Discussing about Communication patterns, problem solving, disability
benefits
• Discussing about relapse and how to identify the early signs of new
episodes
• Improving insight into illness
• Handling expressed emotions and improving communication
• Enhancing adaptive coping to deal with persistent/residual symptoms
• Advise for lifestyle and dietary modifications
Interpersonal and social rhythm therapy (IPSRT)
This therapy is based on the theory that circadian rhythms in
patients with BPAD are vulnerable to external factors and any
disruption of circadian rhythms can precipitate an episode.
Accordingly, it emphasizes on regularizing the social rhythms
or routine of the patient and improving the interpersonal
relationships of the patients so that they can derive more
satisfaction in their social roles. The basic aim is to teach the
patient as to how they can prevent the development of a new
episode (Table-8). Patients are informed that new episodes
can be precipitated by poor medication adherence, stressful
life events and disruption of social rhythms. Patients are
provided with skills as to how they can address interpersonal
problems and issues in the social roles. They are also advised
to maintain a regular daily routine and pay attention to the
day to day stresses which can influence their daily routine
and how they can minimize the impact of these day to day
stressors on their daily routine.
Cognitive Behaviour therapy
Cognitive behaviour therapy (CBT) has been shown to be
efficacious in the management of bipolar depression and
during the maintenance phase of treatment. The basic
goals of CBT is to educate the patient about the illness,
teaching them cognitive behavioural skills for coping with
their illness and psychosocial stressors and problems
arising out of the same, enhance medication and treatment
compliance, monitor the symptoms to prevent relapse.
Family focused interventions
Family forms an integral part of treatment in Indian setting.
They are involved in treatment decision making, supervision
of treatment and monitoring of treatment. However, family
members can also contribute to relapse due to constant
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criticism, poor supervision or over-involvement. High
expressed emotion leads to increased risk of relapse and
poor outcomes. Studies have shown that family focused
interventions can reduce the chances of relapse, improve
medication adherence and reduce the frequency of
depressive episodes. Family focused interventions help
the relatives and patients to integrate the experiences
associated with mood episodes, acknowledging the
vulnerability of having future episodes, accepting the
need to continue with medications, educating the family
about the difference in patients personality and BPAD,
recognising and coping with stress and establishing a
functional relationship (Table-9).
Advise for life style and dietary modifications
As it is well known that patients with BPAD are at increased
risk for cardiovascular mortality and develop metabolic
side effects due to use of psychotropic medications, all
the patients need to be advised about life style and dietary
measures to reduce the risk of metabolic side effects and
cardiovascular morbidity and mortality. These include
physical exercises, dietary modifications and abstinence
from smoking, alcohol and other substances etc.
Rehabilitation
Rehabilitation programmes may be culturally moulded and
adapted to the needs of patients and their families.
Treatment adherence
Mediation and treatment adherence is very important for
management of patients with BPAD. Available evidence
suggests that 20-60% of the patients with BPAD become
non-compliant with medication and drop out of treatment.
Hence, all efforts need to be made to enhance the medication
compliance and treatment adherence. Measures which can
help in improving the compliance are given in table-10.
MANAGEMENT OF DIFFERENT PHASES OF
BIPOLAR DISORDER
Management of BPAD will depend on the phase of illness
in which patient presents to the clinician, i.e., bipolar
depression, bipolar hypomania/mania, first episode
hypomania/mania, mixed episode or clinical remission. In
addition to the phase of illness, factors which may help
in deciding about the pharmacological agent include past
history (number of episodes, type of episodes), comorbidity
(comorbid psychiatric/physical disorders, substance
dependence disorder), past treatment history (response,
side effects) and clinical course (rapid cycling), associated
symptoms (presence of psychotic symptoms) etc. In general
based on the level of evidence, various pharmacological
treatments are categorised as first line agents, second
line agents and third line agents. Selection of an agent
on the basis of current polarity and past history can be of
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Table 8: Basic components of Interpersonal and social
rhythm therapy (IPSRT)
Goals
• Stabilize daily routines and sleep/wake cycles
• Understand the bi‑directional relationship between moods and
interpersonal events
• Minimize or remove the interpersonal problems related to grief, role
transitions, role disputes, interpersonal deficits
Administered in 4 steps
Step‑1
• Give rationale for IPSRT
• History taking with special focus on understanding the relationship of
episodes with interpersonal problems and social routine
• Assess the patient’s current and past interpersonal relationships
• Educating the patient about bipolar disorder
• Identify interpersonal problem areas to focus, for example grief, role
transition, role dispute
• Agree on a topic to discuss
• Initiating the Social Rhythm Metric (i.e., quantify daily rhythms of life)
Step‑2
• Help the patient to establish a regular daily routine and resolve
interpersonal problems
• Analyse the communication patterns, identify the problematic
communication patterns, suggesting alternative communication
methods, role play
• Maintaining social rhythms
Step‑3
• In the continuation or maintenance phase encourage the patient to use
the skills learned in the previous phases of IPSRT
Step‑4
• Termination
Table 9: Basic components of Family focused
interventions
• Assessment of family
• Psychoeducation about symptoms, early recognition, etiology, treatment,
adherence
• Communication skills training ‑ behavioral rehearsal of effective speaking
and listening strategies
• Accepting that patient is vulnerable for having future episodes
• Able to differentiate between patient’s personality and bipolar disorder
• Recognising and coping with stress
• Problem‑solving skills training
• Establishing and maintaining a functional relationship
Table 10: Measures which can improve medication
compliance
• Explain when and how often to take medicines
• Preferably give once a day dosing
• Prescribe minimum number of tablets and medications
• Always ask the patient about kind of formulation (e.g. tablet, capsule etc)
which they would prefer to take
• Check the whole prescription to avoid duplication of medication
• Explain the patient/family that the beneficial effect will be seen only after
days to weeks of intake of medications.
• Explain the patient the need to take medication even after feeling better
• Explanation of side effects- If patients ask about the side effects, explain
the patient about the same.
• Explain the patient as to what to do‑ if they encounter side effects
• Encourage the patient to report side effects
• The need to consult with psychiatrist before discontinuing medications on
their own
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benefit, as in most cases, same agent is continued in the
maintenance phase.
The basic principles of management in the acute phase
are shown in Table-11. Clinicians may focus on carrying
out a comprehensive assessment (psychiatric/medical/
psychosocial), decide about the treatment goals, ensure
safety of the patient and others, decide about the treatment
setting, decide about the choice of medication in liaison
with the patient and the family by taking into account
the clinical and treatment related factors and institute
psychosocial interventions at the earliest so as to provide
comprehensive management. If patient is using alcohol or
other illicit substance, all efforts are to be made to stop
the same. Similarly, if a patient is on antidepressants and
presents with hypomanic/manic or mixed symptoms, these
need to be stopped immediately. Some of the indicators of
inpatient care are shown in Table-12.
All treatment decisions need to be made in consultation
with the patient and or family members and need to be
documented. Whenever mood stabilizers are used, the
required investigations need to be done prior to starting
of mood stabilizers, patient’s serum levels of medications
are to be monitored and other investigations need to be
repeated from time to time as indicated for various mood
stabilizers.
The evidence for efficacy of various agents in management of
different phases of illness (mania, depression, maintenance
phase) vary and it is important to be aware of the same.
Table-13, provides an update on the available level of
evidence for different phases of illness.
MANAGEMENT OF HYPOMANIA/MANIA/
MIXED EPISODE
The goal of management in mania/mixed episode is to
control the aggression, agitation and disruptiveness of
patients at the earliest. Depending of the severity of
symptoms, inpatient care may be considered. If patient is
on antidepressants then this is to be stopped immediately.
In terms of pharmacological management, first line agent
for management of mania may involve use of lithium or
valproate, olanzapine, haloperidol, quetiapine, aripiprazole,
risperidone, paliperidone or ziprasidone as monotherapy.
Typical antipsychotics like haloperidol, trifluoperazine and
chlorpromazine have also been used in the Indian scenario.
These are very useful in the management of irritability,
aggression, impulsivity and psychotic features. However,
these are associated with high incidence of extrapyramidal
reactions. However, there is some evidence to suggest that
combining lithium or valproate with an antipsychotic may be
more effective than any of these agents when used alone.
Indian J Psychiatry 59 (Supplement 1), January 2017
Table 11: Management in the acute phase
•Comprehensive assessment (psychiatric (including alcohol and
substance)/medical/psychosocial)
• Discontinue antidepressants if indicated (patient exhibiting hypomanic/
manic/mixed symptoms)
• Deciding on goals of treatment
• Patients
- Eliminate/reduce symptoms of phase of illness in which patient presents
with and improve the level of functioning
- Promote safety, reduce risk of harm, and reduce stress
• Caregivers
- Minimise caregiver distress
- Offer help to enable them to cope with the illness in their relative
• Both
- Develop a therapeutic alliance and provide opportunities for patients and
- Caregivers to actively engage in treatment
- Offer basic information and support tailored to needs of patients and
caregivers
• Choice of treatment setting
• Choice of medication
- Type and severity of current episode
- Type of past episode (s)
- Predominant polarity
- Past treatment history‑ response, side effects, compliance
• Use of adjunctive medications when indicated
• Use of ECT when indicated
• Psychosocial interventions
• Planning for further treatment‑ Pharmacoprophylaxis
Table 12: Some indications for inpatient care during
acute episodes
Mania/mixed
• Presence of severe agitation or violence which puts the life of others at
risk
• Presence of general medical or comorbid psychiatric conditions that
make outpatient treatment unsafe or ineffective
• Patient not responding to a combination of first line agents
• Treatment‑refractory mania/mixed episode
Depression
• Presence of suicidal behaviour which puts the life of the patient at risk
• Presence of severe agitation or violence which puts the life of others at
risk
• Refusal to eat which puts the life of patient at risk
• Severe malnutrition
• Patient unable to care for self to the extent that she/he requires constant
supervision or support
• Catatonia
• Presence of general medical or comorbid psychiatric conditions that
make outpatient treatment unsafe or ineffective
• Patient not responding to a combination of medications
Among these agents, lithium is thought to have slower onset
of action. Accordingly, it can be said that if the mania is
less severe, monotherapy be considered. However, if mania
is severe and associated with significant disruption than
combination therapy need to be considered. Use of adjunctive
benzodiazepines for short duration may be required.
Patients who refuse medications and are unmanageable may
be given depot antipsychotics like risperidone, paliperidone,
olanzapine or a depot of typical antipsychotic medication.
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Table 13: Comparison of several monotherapy and combination Pharmacotherapies for bipolar disorders
Bipolar Mania Bipolar Depression Mixed episodes Prevention of Prevention of
relapse of depression relapse of mania
Monotherapy
Lithium (Li) √ √ √ √ √
Valproate (V) √ @ √ √ √
Lamotrigine (L) X √ NA √ X
Carbamazepine (C) @ ? X @ @
Oxcarbazepine (O) ? NA NA NA NA
Topiramate (T) X X NA X X
Gabapentin X NA NA X X
Olanzapine (OLZ) √ ? ? √ √
Quetiapine (Q) √ √ NA √ √
Asenapine (ASP) √ NA NA NA ?
Aripiprazole (ARP) √ X ? X √
Risperidone (R) √ NA √ NA @
Paliperidone √ NA ? NA @
Haloperidol @ NA NA NA
Ziprasidone √ X ? NA @
Chlorpromazine ? NA NA NA NA
Clozapine ? NA NA NA NA
Cariprazine NA ? NA NA NA
Lurasidone NA @ NA NA NA
Combination
Li + V √ √ √ √ √
Li + OLZ √ NA NA ? √
Li + R √ NA NA NA √
Li + L NA @ NA NA NA
Li + C NA ? NA NA NA
Li + SSRI NA √ NA NA NA
Li + Venlafaxine NA ? NA NA NA
(Li/V) + ARP ? X NA NA NA
(Li/V) + ASP ? NA NA NA NA
(Li/V) + (Q/ARP/Z) NA NA NA NA √
V + OLZ NA NA ? NA NA
V + SSRI NA √ NA NA NA
OLZ + SSRI NA √ NA √ NA
OLZ + C X NA NA NA NA
R+C X NA NA NA NA
L+Q NA ? NA NA NA
√ – Established efficacy; @ – Efficacy not Established clearly; X – Established that not useful; ? – Evidence limited to open label studies; NA – Evidence not available

If a patient comes with a ‘breakthrough’ hypomanic/manic
episode, then the first step in the management involves
optimization of the ongoing agent. The optimisation can be
done by monitoring the serum levels of agents like lithium
and valproate. If required, additional antipsychotics and
benzodiazepines may be used, depending upon severity of
the episode.
If the first-line agent used in optimal dose fails (lack of
significant clinical benefit after 2 weeks of use), another
first line agent need to be added to the ongoing treatment.
Alternative strategies may include changing lithium to
valproate or vice versa, changing to carbamazepine, adding
antipsychotic medication if not used earlier, changing
the antipsychotic if used earlier. ECT may be considered
if patient is very disruptive, not responding to a trial of
combination of medications, has history of good response
to ECT in the past, pregnancy and those experiencing mixed
episode. Psychosocial interventions like psychoeducation
of patient and family and family focused intervention be
started at the earliest. Psychosocial interventions like CBT
or IPSRT, focused specifically on the patient, should be
considered when patient is cooperative.
MANAGEMENT OF BIPOLAR DEPRESSION
The main goal of management is to achieve euthymia,
normal level of functioning and to avoid switching to
hypomanic/manic episode. Among the various mood
stabilizers, there is ample evidence to suggest that lithium
and lamotrigine may be used as the first line medications in
the management of bipolar depression.
If the patient presents with a breakthrough episode, the
initial strategy is to check the medication compliance and
ensure adequate compliance. If compliance is not an issue,
initial strategy is to optimise the mood stabilizer which the
patient is already getting.

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If the patient is not on any mood stabilizer, than lithium or
lamotrigine may be considered. Among the antipsychotics,
data suggests that quetiapine monotherapy may also be
beneficial. There is evidence for use of olanzapine and
fluoxetine combination too. If the patient does not respond
to monotherapy with mood stabiliser or antipsychotics,
combination of these agents with antidepressants may
be considered. Use of antidepressants without the use of
concurrent mood stabilizer or an atypical antipsychotic is
to be avoided. Benzodiazepines may be used as per the
need. Psychosocial intervention in the form of CBT may also
be considered when the depression is of mild to moderate
severity. ECT may be considered, if depression is severe,
in presence of suicidality, risk of harm to others, catatonic
symptoms, psychotic symptoms, patient is pregnant, when
use of various psychotropics is limited due to concurrent
medical illnesses. There is preliminary evidence to suggest
the beneficial effect of transcranial magnetic stimulation
and direct cranial stimulation.
RAPID CYCLING AFFECTIVE DISORDER
Rapid cycling affective disorder (RCAD) is
characterised by having 4 or more episodes
(depression/mania/hypomania/mixed) in a single year.
These episodes should be separated from each other by
partial or full remission for at least 2 months or a switch
to an episode of opposite polarity. Many risk factors
(Table-14) have been identified for development of
RCAD. Accordingly, the first step in the management of
RCAD is to evaluate the patients for underlying medical
conditions which may be contributing to the RCAD. Among
medications, use of antidepressants has been shown to
increase cycling.
In terms of psychotropics, there is evidence to suggest that
lithium or valproate may be used as the first line agents.
Other mood stabilizers which can be considered include
lamotrigine. If patient does not respond to monotherapy,
then combination of mood stabilizers or a combination
of mood stabilizer and antipsychotic medication may be
considered.
MAINTENANCE TREATMENT FOR BIPOLAR
DISORDER
The primary goal of maintenance treatment is to prevent the
recurrence of episode of either polarity, reduce/eliminate
the residual symptoms and improve the overall functioning
of the patient. In terms of pharmaco-therapeutic agents, best
evidence for maintenance treatment is available for lithium
and valproate. In recent years evidence has also emerged for
use of olanzapine and quetiapine in prevention of recurrence
of both depressive and manic episodes. However, these may
be avoided because of associated higher risk of metabolic
Indian J Psychiatry 59 (Supplement 1), January 2017
Table 14: Risk factors for Rapid Cycling Affective
Disorder
Risk factors for RCAD
• Hypothyroidism
• Long term aggressive use of antidepressants
• Comorbid substance use
• Minor tranquilizer/stimulant or caffeine abuse
• Cyclothymic and hyperthymic temperament
• Female gender
• Menopause
• Temporal lobe dysrhythmias
• Several episodes/stressors as an effect of kindling
• Onset of illness as depression
• Frequent and more depressive episodes
• ? COMT/BDNF gene abnormality
• ? Biological rhythm disturbances like wakefulness, light exposure
side effects. Long acting risperidone has been shown to
be beneficial in prevention of recurrence. Lamotrigine has
been shown to be efficacious in prevention of depressive
episodes, but not for prevention of manic episodes.
Olanzapine, aripiprazole, ziprasidone and asenapine has
been shown to be of benefit in prevention of recurrence
of manic episodes, but not for depressive episodes.
Carbamazepine has also been shown to be effective in
prevention of recurrence; however, it is less preferred
compared to lithium and valproate because of its side effect
profile and drug interactions. Studies have also evaluated
the efficacy of lithium and valproate in combination with
various antipsychotics. Besides use of pharmacotherapy,
there is evidence to suggest the beneficial role of adjunctive
psychosocial intervention in the management of BPAD.
Maintenance ECT may also be considered in patients who
have responded to ECT during their acute episodes.
The general principle of management during the
maintenance phase of treatment is to continue the
medication started during the acute phase of illness.
Accordingly, while selecting the agent during the acute
episode, clinicians may take into consideration the patient’s
preference, clinical factors which may influence the long
term outcome, recurrence of episodes and side effects.
If the patients have more manic episodes then one may
prefer lithium, valproate or carbamazepine while for more
depressive episodes one may consider Lithium, lamotrigine
or quetiapine. In severe cases, combination of lithium and
valproate may be considered.
It is important to note that patients with mood disorders are
more vulnerable to extrapyramidal side effects like tardive
dyskinesia with long term use of antipsychotics, especially
typical antipsychotics. Patients who have been treated with
a combination of lithium and antipsychotic or valproate and
antipsychotic medication, the need for continued use of
antipsychotic need to be reassessed on the basis of longitudinal
course. Similarly, stoppage of antidepressants needs to be
considered once bipolar depression remits. Combination
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Bipolar Hypomania/Mania/Mixed Episode

Currently on treatment (Breakthrough Currently not on treatment

episode/switch in presence of First line therapy:
antidepressants) • Monotherapy: Lithium, valproate, antipsychotics
• Stop antidepressant- if patient • Combination: Lithium+ antipsychotic/
is getting the same valproate+antipsychotic
• Optimize the dose of the mood • Use Benzodiazepines as per the need
stabilizer which the patient is on • Use of depot antipsychotic may be considered
• If the symptoms do not respond if patient is not willing to take oral medications
to optimisation of the dose or are • ECT: may be considered with monotherapy or
severe, consider adding an combination therapy as per the indication
antipsychotic medication
• Benzodiazepines may be used
depending upon the need
Failure of adequate trial of
first line treatment

Second line therapy:

Failure of adequate trial of
first line treatment
Monotherapy: Change lithium to lamotrigine or vice
versa
Combination:
• Add antipsychotic if not used
• Change from Lithium+ antipsychotic to
valproate+antipsychotic medication
• Change from Valproate+antipsychotic to
lithium+antipsychotic medication
• Continue lithium/valproate and change the
antipsychotic medication
• Consider changing lithium/valproate to carbamazepine
• Use Benzodiazepines as per the need
• Use ECT if not considered earlier
• Consider clozapine if mania is treatment refractory
• Consider other agents

Figure 2: Management of Hypomania/ Mania/Mixed Episode

therapy during the maintenance phase is to be considered
only for those who have not responded to the optimal dose of
monotherapy during the maintenance phase of illness.
SPECIAL SITUATIONS
Clinicians often encounter certain clinical situations which
either require special attention or can influence treatment
decisions. Management of these situations is summarised
in table-15.
SIDE EFFECTS AND THEIR MANAGEMENT
Various classes of psychotropic medications used for the
management of BPAD are associated with many side effects,
which require intervention. The side effects associated
with antipsychotics are discussed in the clinical practice
guidelines for schizophrenia. The recommendations made for
monitoring of metabolic side effects associated with various
atypical antipsychotics may also be followed in patients with
BPAD, if long term antipsychotic medications are considered.
Use of lithium is associated with multiple side effects. These
side effects can be classified on the basis of occurrence (i.e.,
those occurring during the early or late phase of treatment)
and frequency (Common, uncommon, rare and very rare)
(Table-16). Most of these side effects can be managed with
reduction in dose of medication or shifting to a sustained
release preparation as the first line strategy.
The common management strategies for the side effects
associated with lithium, valproate and carbamazepine are
shown in Table-17.

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Bipolar Depression

Already on treatment Not on treatment

Valproate, Lithium First line therapy:

Olanzapine, Lamotrigine • Monotherapy/combination: Lithium, lamotrigine,
Risperidone, Antipsychotics quetiapine, olanzapine-fluoxetine combination,
other valproate+lithium, valproate+ antidepressant
atypicals • Combination: mood stabiliser/antipsychotics+
antidepressant
• Psychosocial intervention: if depression is
mild to moderate
• ECT: may be considered with monotherapy or
combination therapy as per the indication
Optimise the Optimise the
dose dose

• Add antidepressant – bupropion, SSRI

• Add or change to lithium, lamotrigine or quetiapine
• Consider changing from one agent (lithium/lamotrigine/quetiapine) to other
• Consider Valproate along with lithium or antidepressant
• Consider combinations
• Consider psychosocial intervention if the depression is mild to moderate
• Consider ECT as per the indication
• Consider rTMS, tDCS

Figure 3: Management of Bipolar Depression

Table 15: Issues related to special situations

Special Strategies
situation
Suicidality • Risk of suicide is high in patients with BPAD.
• Suicidal behaviour is seen during the depressive episode, mixed episode and also in manic episode. Suicide have also been reported
during the euthymic phase
• Clinicians need to carefully evaluate the patients for suicidal ideations, plans, suicidal attempts at every follow‑up.
• High risk management be instituted and inpatient management may be considered if the patient is at high risk.
• Psychoeducation of patient and family need to focus on discussing about warning signs of suicide. Patients experiencing severe distress
due to a feeling of loss, stigma etc., are to be provided psychological support and monitored closely.
• Use of lithium has been shown to lower the risk of suicide.
• ECT is an important therapeutic option in patients at high risk of suicide during an acute episode.
Catatonia • Catatonic features may be seen in both depressive and manic phase of illness.
• Whenever a patient with BPAD presents with catatonia, all possible differential diagnosis for catatonia need to be considered.
• Investigate to rule out organic cause (s).
• Initial management may involve use of benzodiazepines, especially lorazepam, which leads to symptomatic relief in significant proportion of cases.
• In case the catatonia does not respond to benzodiazepines or relapse after stopping benzodiazepines, ECT is to be considered.
Psychotic • Psychotic symptoms are seen in a significant proportion of patients with BPAD.
features • When present, use of antipsychotics is warranted.
Violence and • All patients, especially those in mania need to be evaluated for violence and dangerousness during every assessment, especially during
Aggression the acute phase of illness.
• Whenever a patient is found to have serious threat for violence or exhibits violence, inpatient management may be considered.
• Injectable antipsychotics like haloperidol or lorazepam can be used for management of violence and aggression.
Comorbid • Substance use can precipitate an episode, increase the frequency of episode, may be associated with RCAD, higher risk for suicide, poor
Alcohol and response to treatment, longer time to achieve remission, can influence the choice of medication, lead to higher vulnerability for side effects.
Substance • Both BPAD and substance use disorders need to be treated concurrently.
use Disorders • Efforts need to be made to keep the patient abstinent from alcohol and other substance(s), both during the acute episodes and during the
maintenance phase of illness.
Comorbid • Patients of BPAD have high rate of comorbid anxiety disorders, ADHD etc.
Psychiatric • Comorbid disorders, may not be evident during the acute episodes. Accordingly, patients need to be evaluated during the maintenance
disorders phase for any kind of comorbid psychiatric disorders.
• Management of comorbid disorders need to be done along with concurrent management of BPAD.
Comorbid • Patients with bipolar disorder have high rate of physical comorbidities.
Physical • All patients need to receive thorough assessment for possible physical illnesses and depending on the feasibility may be investigated as
illnesses per the requirement.
• Those with comorbid physical illnesses are to be continuously monitored during all the phases of treatment.
• Comorbid physical illnesses and concomitant medications also need to be taken into account while selecting the treatment setting and
antipsychotic medication per se.
Contd...
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Shah, et al.: CPGs for bipolar disorders

Table 15: Contd...
Special Strategies
situation
Perioperative • When used during the perioperative period, lithium can contribute to hemodynamic instabilities, interfere with sodium and potassium
period metabolism, and the renal excretion of lithium can be reduced in presence of renal complications. Therefore it is recommended that
lithium need to be discontinued prior to surgery.
• Postoperatively, when the patient is hemodynamically stable, is able and allowed to drink, and is not on potentially interfering drugs, the
medication may be restarted gradually.
Pregnancy • Mood stabilizers, including lithium are considered to be teratogenic and associated with higher rate of congenital malformations.
• Pregnancy is to be planned.
• Whenever feasible, exposure to lithium, valproate, carbamazepine, lamotrigine need to be avoided during pregnancy. Hence, attempt
need to be made to discontinue these medications.
• If patient is not able to tolerate the discontinuation of medication, than the pros and cons of continuation of the medications during the
first trimester need to be discussed and documented.
• If required, lithium may be used during second and third trimester of pregnancy; Use the minimal optimal dose.
• If required, antipsychotics, especially high potency typical antipsychotics may be considered.
• Use folic acid during pregnancy.
• If patient is receiving mood stabilizer during the pregnancy – monitor alpha feto‑protein levels at 20 weeks.
Post‑partum • There is high risk of relapse during the post‑partum period.
& Breast • The new‑born be evaluated thoroughly, if the mother was on psychotropics during pregnancy for malformations, drug overdose and withdrawal.
feeding • Lithium need to be used with caution during the postpartum.
• When valproate is used during the post‑partum, liver function tests and haemogram of the neonate need to be monitored adequately.
Elderly • Have high rates of comorbid medical illnesses and substance use disorders.
• More sensitive to side effects of medications, at risk for fall and fracture of hip.
• May develop cognitive deficits with use of lithium or benzodiazepines.
• Start low and go slow.
Children & • Have high rates of comorbidity in the form of Attention‑hyperkinetic disorder (ADHD), conduct disorder, substance use disorders.
Adolescents • At times it may be difficult to distinguish between symptoms of mania and ADHD.
• Take longer time to stabilize.
• Data on use of lithium before 12 years of age is not available and use of lithium prior to this age is not recommended.
• Start at lower doses and titrate slowly.

MANAGEMENT OF TOXICITY Table 16: Side effects of lithium

Early onset side effects Common side effects
Among the lithium, valproate and carbamazepine, valproate Weight gain Short term dose related
has a wide therapeutic window. Lithium and carbamazepine Tremor Nausea, diarrhea, epigastric pain
toxicity may be fatal and are medical emergencies. The Anorexia, Nausea, Diarrhea Tremor
Aggravation of cutaneous Thirst, polyuria
therapeutic range for serum lithium levels varies from conditions Metallic taste
0.4 to 1.2 meq/litre. Toxic effects of lithium are usually Mild thirst Long term side effects
seen when the serum levels of lithium rise above 1.5meq/ Polyuria Weight gain
litre. When the levels exceed 2meq/litre, life threatening Late onset side effects Hypothyroidism in women
Nephrogenic diabetes insipidus Reduction in eGFR
side effects may emerge. Various signs and symptoms Hypothyroidism Tubular dysfunction
of toxicity with lithium, valproate and carbamazepine Thyroiditis Uncommon side effects
are shown in Table-18.Management of lithium toxicity Hyperthyroidism Fluid retention (oedema)
is an acute emergency and involves stoppage of lithium, Cognitive dulling Hypothyroidism
Rare side effects
maintaining the airways, maintaining an intravenous line
Acne
and use of haemodialysis if serum lithium levels are more Psoriasis
than 2.5 mEq/Litre. However, in patients with end stage Hair loss
renal disease, haemodialysis may be considered in levels Fatigue
below 2.5mEq/litre as well. Arrhythmia
Cognitive deficit
Seizures
Management of valproate toxicity also involve use of Sexual side effects
haemodialysis. However, there are no clear guidelines for Very Rare side effects
the same. Management of carbamazepine intoxication ↑WBC count
↑serum Ca++, Mg++
involves gastric lavage, hemoperfusion and use of supportive ↑ parathyroid hormone
measures. ↑blood sugar
Benign intracranial hypertension
Financial support and sponsorship Parkinsonism disease’s like
symptoms
Nil.

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Shah, et al.: CPGs for bipolar disorders

Table 17: Management of side effects of mood stabilizers

Side effects Management
Lithium
Dose‑related side effects: polyuria, polydipsia, weight gain, Reduce the dose and/or shift to once a daily dose of medications, if the side effects
cognitive problems (e.g., dulling, impaired memory, poor still persist than use other medications:
concentration, confusion, mental slowness), tremor, sedation Tremors: beta‑blockers
or lethargy, impaired coordination, gastrointestinal distress Polyuria, polydipsia, edema: diuretics
(e.g., nausea, vomiting, dyspepsia, diarrhoea), hair loss, benign Acne: Topical antibiotics, retinoic acid
leukocytosis, acne, and edema Gastrointestinal side effects: give lithium after meals, change to lithium citrate
Electrocardiogram (ECG) Changes Cardiac Side effects: Reduce the dose, if the abnormalities persist, may have to stop
lithium in consultation with the cardiologist depending on the severity of the cardiac
conduction abnormalities
Renal Side effects: Impaired concentrating capacity, interstitial Renal side effects: Diuretics for impaired concentrating capacity‑ thiazides, amiloride
fibrosis, tubular atrophy
Hypothyroidism Hypothyroidism: Not an indication for stopping lithium, add levothyroxine
Dermatological: Reduce the dose, appropriate dermatological treatment, if does not
respond then may consider stopping lithium
Psoriasis Inositol supplementation, TNF α inhibitors (Etanercept), Conventional treatment of
Psoriasis (Topical corticosteroids, Keratolytics, Vitamin D analogues, Oral retinoids,
Psoralen, Ultraviolet A (PUVA) therapy , Methotrexate)
May have to consider stopping lithium in treatment resistant cases of psoriasis
Valproate
Dose‑related side effects: Gastrointestinal distress (nausea, Resolve with reduction in dose, if persist, then
vomiting, diarrhoea etc), tremor, sedation, benign hepatic GI disturbances: change of preparation from Valproic acid to Divalproex,
transaminase elevations Proton‑pump blockers, Histaminic blockers
Tremors: beta‑blockers
Hepatotoxicity Discontinuation of valproate
Leukopenia, Thrombocytopenia Discontinuation of valproate
Hair loss, increased appetite, weight gain Dietary restriction for increased appetite and weight gain
Polycystic ovarian disease May have to discontinue valproate if other options are available, metformin
Hepatic failure, haemorrhagic pancreatitis, and Discontinuation of valproate
agranulocytosis
Carbamazepine
Ophthalmological: diplopia, blurred vision Reduce the dose
Gastrointestinal: nausea Reduce the dose
Neurological: ataxia Reduce the dose
Dermatological: skin rashes Reduce/Stop Carbamazepine
Haematological: leukopenia, thrombocytopenia Mild leukopenia may resolve on its own, in case of severe leukopenia, stop the
medication
Electrolyte imbalance: Hyponatremia May require discontinuation of carbamazepine
Endocrine: hypothyroidism May require addition of levothyroxine
Serious side effects: agranulocytosis, aplastic anemia, Stop Carbamazepine, manage the medical condition
thrombocytopenia, hepatic failure,
Stevens‑Johnson syndrome, pancreatitis

Table 18: Signs and symptoms of Toxicity of lithium, Table 18: Contd...

valproate and Carbamazepine Carbamazepine
Lithium levels 1.5‑2‑5 meq/litre Dizziness, Ataxia, Sedation, Nystagmus, Ophthalmoplegia, Cerebellar
Neurological: Fine tremors, Apathy, Fatigue, Muscle weakness, and extrapyramidal signs, Impaired consciousness, Seizures, Respiratory
Hyperreflexia, Incontinence, Gait disturbances depression, Stupor, Coma, Tachycardia, Arrhythmia, Cardiac conduction
Gastrointestinal: nausea, vomiting, diarrhoea disturbances, Hypotension
Cardiovascular changes: Bradycardia, T‑wave changes, sinoatrial block, AV
block
Lithium levels >2.5 meq/litre Conflicts of interest
Neurological: course tremors, slurring of speech, dysarthria, ataxia, There are no conflicts of interest.
hypertonia, spasticity, rigidity, myoclonus, seizures, stupor, coma,
permanent neurological deficits
REFERENCES
Gastrointestinal: nausea, vomiting, diarrhoea
Cardiovascular changes: bradycardia, T‑wave changes, sinoatrial block,
1. Merikangas KR, Jin R, He JP et al. Prevalence and correlates of bipolar
AV block, hypotension
spectrum disorder in the world mental health survey initiative. Arch Gen
Renal: Renal failure Psychiatry 2011; 68: 241–251.
Valproate 2. Sidor MM, Macqueen GM. Antidepressants for the acute treatment
Somnolence, Heart block, Coma of bipolar depression: a systematic review and meta-analysis. J Clin
Psychiatry 2011; 72: 156–167.
Contd.. 3. Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Möller HJ,

Indian J Psychiatry 59 (Supplement 1), January 2017 S65

[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Shah, et al.: CPGs for bipolar disorders
& Kasper S. The World Federation of Societies of Biological Psychiatry
(WFSBP) guidelines for the biological treatment of bipolar disorders:
update 2012 on the long-term treatment of bipolar disorder. The World
Journal of Biological Psychiatry 2013; 14(3), 154-219.
4. Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M,
Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT)
and International Society for Bipolar Disorders (ISBD) collaborative
update of CANMAT guidelines for the management of patients with bipolar
disorder: update 2013. Bipolar disorders; 2013;15(1), 1-44.
5. National Institute for Health and Care Excellence. Bipolar disorder: The
assessment and management of bipolar disorders in adults, children and
young people in primary and secondary care. Draft for consultation, April
2014. http://www.nice.org.uk/
6. American Psychiatric Association. Guideline Watch: Practice guideline for
the treatment of patients with bipolar disorder, 2ndedn. Washington DC:
American Psychiatric Association; 2005.
7. Goodwin GM. Evidence –based guidelines for treating bipolar disorder:
revised second edition- recommendations from the British Association for
Psychopharmacology. J Psychopharmacol 2009; 23:346-388.
8. Cipriani Andrea, et al. “Comparative efficacy and acceptability of antimanic
drugs in acute mania: a multiple-treatments meta-analysis.” The Lancet
378.9799 (2011): 1306-1315.
9. Fountoulakis KN, Kontis D, Gonda X, Yatham LN. A systematic review of
the evidence on the treatment of rapid cycling bipolar disorder. Bipolar
disorders; 2013; 15(2), 115-137.
10. Rao PG. An overview of Indian research in bipolar mood disorder. Indian
Journal of Psychiatry. 2010;52(Suppl1):S173-S177.
11. Avasthi A, Grover S, Aggarwal M. Research on mood stabilizers in India.
Indian J Psychiatry 2010;52, Suppl S3:355-61
12. Grover S, Avasthi A, Sinha V, Lakdawala B, Bathla M, Sethi S,
Mathur D M, Kathuria P, Shah S, Baalasubramanian D S, Agarwal V, Deka
K. Indian Psychiatric Society multicentric study: Prescription patterns of
psychotropics in India. Indian J Psychiatry 2014;56:253-64
13. Grover S, Avasthi A. Mood stabilizers in pregnancy and lactation. Indian J
Psychiatry 2015;57, Suppl S2:308-23
14. Tighe SK, Mahon PB, Potash JB. Predictors of Lithium Response in Bipolar
Disorder. Therapeutic Advances in Chronic Disease. 2011; 2(3):209-226.
15. Cipriani A, Hawton K, Stockton S, & Geddes JR. Lithium in the prevention of
suicide in mood disorders: updated systematic review and meta-analysis.
BMJ. 2013; 346:f3646.
16. Malhi GS, Tanious M. Optimal frequency of lithium administration in the
treatment of bipolar disorder: clinical and dosing considerations. CNS
Drugs 2011; 25(4): 289-98.
17. Ng F, Hallam K, Lucas N, Berk M. The role of lamotrigine in the management
of bipolar disorder. Neuropsychiatric disease and treatment, 2007; 3(4), 463.
18. Bowden, C. L., Asnis, G. M., Ginsberg, L. D., Bentley, B., Leadbetter, R.,
& White, R. Safety and tolerability of lamotrigine for bipolar disorder. Drug
safety, 2004; 27(3), 173-184.
19. Tränkner A, Sander C, Schönknecht P. (2013). A critical review of the
recent literature and selected therapy guidelines since 2006 on the use
of lamotrigine in bipolar disorder. Neuropsychiatric disease and treatment,
2013; 9, 101.
20. Tohen M, Zhang F, Taylor CC, Burns P, Zarate C, Sanger T, Tollefson, G. A
meta-analysis of the use of typical antipsychotic agents in bipolar disorder.
Journal of affective disorders, 2001; 65(1), 85-93.
21. Gao K, Gajwani P, Elhaj O, Calabrese JR. Typical and atypical
antipsychotics in bipolar depression. The Journal of clinical psychiatry,
2005; 66(11), 1376-1385.
22. Gigante AD, Lafer B, Yatham LN. Long-acting injectable antipsychotics for
the maintenance treatment of bipolar disorder. CNS drugs, 2012; 26(5),
403-420.
S66
23. De Berardis D, Marini S, Carano A, Padovan Lang A, Cavuto M, Piersanti M,
Di Giannantonio M. Efficacy and safety of long acting injectable atypical
antipsychotics: a review. Current clinical pharmacology, 2013; 8(3),
256-264.
24. Chou YH, Chu PC, Wu SW, Lee JC, Lee YH, Sun IW, Yen YC. A Systemic
Review and Experts’ Consensus for Long-acting Injectable Antipsychotics
in Bipolar Disorder. Clinical Psychopharmacology and Neuroscience,
2015; 13(2), 121.
25. Joffe RT, MacQueen GM, Marriott M, Robb J, Begin H, Young LT. Induction
of mania and cycle acceleration in bipolar disorder: effect of different
classes of antidepressant. ActaPsychiatricaScandinavica, 2002;105(6),
427-430.
26. Thase ME, Sachs GS.. Bipolar depression: pharmacotherapy and related
therapeutic strategies. Biological psychiatry, 2000; 48(6), 558-572.
27. Gijsman HJ, Geddes JR, Rendell JM, Nolen WA, Goodwin GM.
Antidepressants for bipolar depression: a systematic review of randomized,
controlled trials. American Journal of Psychiatry 2014; 161: 1537-47.
28. Henry C, Sorbara F, Lacoste J, Gindre C, Leboyer M.Antidepressant-induced
mania in bipolar patients: identification of risk factors. Journal of Clinical
Psychiatry, 2001; 62(4), 249-255.
29. TohenM, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C,Breier
A. Efficacy of olanzapine and olanzapine-fluoxetine combination in the
treatment of bipolar I depression. Archives of general psychiatry, 2003;
60(11), 1079-1088.
30. McElroy SL. Prescribing antidepressants for bipolar depression: what
does the evidence say?.The Journal of clinical psychiatry, 2014; 75(9),
e24-e24.
31. Silverstone T. Moclobemide vs. imipramine in bipolar depression: a
multicentre double‐blindclinical trial. ActapsychiatricaScandinavica,
2001; 104(2), 104-109.
32. Nivoli AM, Colom F, Murru A, Pacchiarotti I, Castro-Loli P,
González-Pinto A,Vieta E. New treatment guidelines for acute bipolar
depression: a systematic review. Journal of affective disorders, 2011;
129(1), 14-26.
33. Vázquez GH, Tondo L, Undurraga J, Baldessarini RJ. Overview of
antidepressant treatment of bipolar depression. International Journal of
Neuropsychopharmacology, 2013; 16(7), 1673-1685.
34. Schöttle D, Huber CG, Bock T, Meyer TD. Psychotherapy for bipolar
disorder: a review of the most recent studies. Current opinion in psychiatry,
2011; 24(6), 549-555.
35. Scott JAN, Paykel E, Morriss R, Bentall R, Kinderman P, Johnson T,
Hayhurst H. Cognitive–behavioural therapy for severe and recurrent
bipolar disorders. The British Journal of Psychiatry, 2006; 188(4),
313-320.
36. Miklowitz DJ. A review of evidence-based psychosocial interventions for
bipolar disorder. Journal of Clinical Psychiatry, 2006; 67, 28.
37. Chanpattana W. Combined ECT and clozapine in treatment-resistant
mania. J ECT 2000; 16:204-207.
38. Devanand DP, Polanco P, Cruz R, Shah S, Paykina N, Singh K, and Majors
L: The efficacy of ECT in mixed affective states. J ECT 2000; 16:32-37.
39. Mukherjee S, Sackeim HA, Schnur DB. Electroconvulsive therapy of acute
manic episodes: a review of 50 years’ experience. Am J Psychiatry 1994;
151:169-176.
40. Ismail Shihabuddeen TM, Gopinath PS. Group meetings of caretakers
of patients with schizophrenia and bipolar mood disorders. Indian J
Psychiatry 2005;47:153-6.
41. Durgam S, Starace A, Li D, Migliore R, Ruth A, Németh G, Laszlovszky I.
The efficacy and tolerability of cariprazine in acute mania associated with
bipolar I disorder: a phase II trial. Bipolar Disord. 2015;17:63-75.
42. Muneer A. The Treatment of Adult Bipolar Disorder with Aripiprazole: A
Systematic Review. Cureus. 2016 Apr; 8(4): e562.
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CLINICAL PRACTICE GUIDELINES

Clinical Practice Guidelines for the management of Depression

Shiv Gautam, Akhilesh Jain1, Manaswi Gautam2, Vihang N. Vahia3, Sandeep Grover4
Director Professor, Director, Gautam Hospital & Research Center, Consultant Psychiatrist Gautam Hospital and Research
Center, 1Specialist Psychiatry ESI Hospital, 2Gautam Hospital and Research Center and Gautam Institute of Behavioural
Sciences and Alternative Medicine, Jaipur, 3Consultant Psychiatrist, Gaur Medical Health Clinic, Ajmer, 4Additional
Professor, Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India

ASSESSMENT AND EVALUATION (table-1)

Participants of expert group on CPG for Depression
Gautam Saha, I.D Gupta, Navendu Gaur, Tushar Jagawat,
Anita Gautam, T. S Sathyanarayana Rao
INTRODUCTION
Depression is a common disorder, which often leads to
poor quality of life and impaired role functioning. It is
known to be a major contributor to the global burden
of diseases and according to World Health Organization
(WHO), depression is the fourth leading cause of disability
worldwide and it is projected that by 2020, it will be
the second most common leading cause of disability.
Depression is also associated with high rates of suicidal
behaviour and mortality. When depression occurs in the
context of medical morbidity, it is associated with increased
health care cost, longer duration of hospitalization, poor
cooperation in treatment, poor treatment compliance and
high rates of morbidity. Depression is also known to be
associated with difficulties in role transitions (e.g., low
education, high teen child-bearing, marital disruption,
unstable employment) and poor role functioning (e.g.,
low marital quality, low work performance, low earnings).
It is also reported to be a risk factor for the onset and
persistence of a wide range of secondary disorders.
Available data also suggests that between one-third
and one-half of patients also experience recurrence of
depressive episodes.
Address for correspondence:
Dr. Sandeep Grover, Additional Professor, Department of
Psychiatry, PGIMER, Chandigarh, India.
E-mail: drsandeepg2002@yahoo.com
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Management of depression involves comprehensive
assessment and proper establishment of diagnosis. The
assessment must be based on detailed history, physical
examination and mental state examinations.History must be
obtained from all sources, especially the family. The diagnosis
must be recorded as per the current diagnostic criteria.
Depression often presents with a combination of
symptoms of depressed mood, loss of interest or pleasure,
decreased energy and fatigue, reduced concentration
and attention, reduced self-esteem and self-confidence,
ideas of guilt and unworthiness, bleak and pessimistic
views of the future, ideas or acts of self-harm or suicide,
disturbed sleep and diminished appetite. Depending on
the severity of depression some of these symptoms may
be more marked and develop characteristic features that
are widely regarded as having special clinical significance.
These symptoms are known as somatic symptoms of
depression and include symptoms of loss of interest or
pleasure in activities that are normally enjoyable, lack of
emotional reactivity to normally pleasurable surroundings
and events, waking up in the morning 2 hours or more
before the usual time, depression worse in the morning,
objective evidence of definite psychomotor retardation
or agitation (remarked on or reported by other people),
marked loss of appetite, weight loss (often defined as 5%
or more of body weight in the past month) and marked
loss of libido. It is important to note that for the diagnosis
of depressive disorder these symptoms need to be present
for at least 2 weeks and need to be associated with
psychosocial dysfunction.
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DOI:
How to cite this article: Gautam S, Jain A, Gautam M,
Vahia VN, Grover S. Clinical Practice Guidelines for the
10.4103/0019-5545.196973
management of Depression. Indian J Psychiatry 2017;59:34-50.

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Gautam, et al.: CPGs for depression

Table 1: Components of assessment and evaluation
Basic assessments
• Complete history with information from all possible sources
• Physical examination‑ look for thyroid swelling, evidence for
malnutrition or any specific nutritional deficiency
• Record blood pressure, weight and wherever indicated body mass index
and waist circumference
• Mental state examination
• Establish diagnosis according to current diagnostic criteria
• Differential diagnosis by ruling out secondary depression
• Rule out bipolar disorder, premenstrual dysphoric disorder
• Assess the severity, specifier, subtype of depression
• Areas to be evaluated: symptom‑severity,
symptom‑dimensions (psychotic symptoms, catatonic symptoms,
melancholic symptoms, reverse vegetative symptoms and cognitive
symptoms), comorbid physical, psychiatric and substance use
conditions, risk of harm to self and others, level of functioning and
socio‑cultural milieu of the patient
• Basic investigations: haemogram, blood sugars and lipid levels, liver
functions, renal functions, thyroid function test (if indicated)
• Assessments of caregivers: knowledge and understanding of the illness,
attitudes and beliefs regarding treatment, impact of the illness on them,
personal and social resources
• Ongoing assessments: response to treatment, side effects, treatment
adherence, the impact of patient’s immediate environment, disability
assessments, other health‑care needs, ease of access and relationship
with the treatment team
Additional/Optional assessments
• Use of standardized rating scales to rate all aspects of the illness
• Neuroimaging especially in those with first‑episode of depression seen
in late or very late age; those have neurological signs, those having
treatment resistant depression
Table 2: Some of the physical illnesses commonly
associated with depression
• Epilepsy • Disease
• Post stroke • Depression in Malignancy
• Parkinson’s Disease • Hypothyroidism
• Multiple Sclerosis • Hyperthyroidism
• Degenerative Brain Disease • Hyperparathyroidism
• Alzheimer’s Disease • Cushing’s Syndrome
• Coronary Artery • Addison’s disease
• Diabetes mellitus
Some of the patients with depression may present with
predominant complaints of aches, pains and fatigue and
they may not report sadness of mood on their own. A careful
evaluation of these patients often reveals the underlying
features of depression. However, it is important to note that
many patients with depression will also have associated anxiety
symptoms. With increasing severity of depression patients may
report psychotic symptoms and may also present with catatonic
features. Thorough assessment also ought to focus on evaluation
for comorbid substance abuse/dependence. Careful history of
substance intake need to be taken to evaluate the relationship
of depression with substance intoxication, withdrawal and
abstinence. Whenever required appropriate tests like, urine or
blood screens (with prior consent) may be used to confirm the
existence of comorbid substance abuse/dependence.
Many physical illnesses are known to have high rates of
depression. In some situations the physical illnesses have
causative role in development of depression, whereas in other
situations the relationship/co-occurrence is due to common
etiology. Some of the physical illnesses commonly associated
with depression are listed in Table-2. When depression
occurs in relation to physical illness attempt may be made
to clearly delineate the symptoms of depression and physical
illness. Further, while making the diagnosis, it maybe clearly
mentioned as to which diagnostic approach [i.e., inclusive
approach (symptoms are counted whether or not they might be
attributable to physical illness), substitute approach (nonsomatic
symptoms are substituted with somatic symptoms), exclusive
approach (somatic symptoms are deleted from the diagnostic
criteria) or best estimate approach] was followed. Further,
while reviewing the treatment history of medical illnesses,
medication induced depression must be kept in mind, as
many medications are known to cause depression (Table-3).
It is always important to take the longitudinal life course
perspective into account to evaluate for previous episodes
and presence of symptoms of depression amounting to

Table 3: Medications known to cause depression

Cardiovascular drugs Azathioprine Ampicillin Penicillin G Benzodiazepines Efavirenz
ACE inhibitors Bleomycin Chloramphenicol procaine Chloral hydrate Enfuvirtide
Calcium channel Cisplatin Methylphenidate (Ritalin) Streptomycin Ethanol Saquinavir
blockers Cyclophosphamide Chloroquine Sulfonamides Other drugs Zidovudine
Clonidine Doxorubicin Clofazimine Tetracycline Choline Anticonvulsants
Digitalis Vinblastine Cycloserine Trimethoprim Cimetidine Ethosuximide
Guanethidine Vincristine Cyclosporine Hormones Disulfiram Phenobarbital
Hydralazine Antiparkinsonian Dapsone Adrenocorticotropin Lecithin Phenytoin
Methyldopa drugs Ethambutol Anabolic steroids Methysergide Primidone
Procainamide Amantadine Ethionamide Glucocorticoids Phenylephrine Tiagabine
Propranolol Bromocriptine Foscarnet Oral contraceptives Physostigmine Vigabatrin
Reserpine Levodopa Ganciclovir Antipsychotic drugs Ranitidine Anti‑inflammatory
Thiazide diuretics Stimulants Griseofulvin Fluphenazine Statins agents
Guanabenz Amphetamines Isoniazid Haloperidol Tamoxifen NSAIDS
Zolamide diuretics withdrawal) Metoclopramide Sedatives and Antiretroviral drugs
Chemotherapeutics Caffeine Metronidazole antianxiety Atazanavir
6‑Azauridine Cocaine (withdrawal) Nalidixic acid drugs
Asparaginase Anti‑infective agents Nitrofurantoin Barbiturates

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Gautam, et al.: CPGs for depression

dysthymia. Evaluation of history also takes into consideration
the relationship of onset of depression with change in
season (seasonal affective disorder), peripartum period and
phase of menstrual cycle. Further, the longitudinal course
approach may also take into account response to previous
treatment and whether the patient achieved full remission,
partial remission and did not respond to treatment.
induced switch. Presence of psychotic features, marked
psychomotor retardation, reverse neurovegetative
symptoms (excessive sleep and appetite), irritability of
mood, anger, family history of bipolar disorder and early
age of onset need to alert the clinicians to evaluate for the
possibility of bipolar disorder, before concluding that they
are dealing with unipolar depression.

An important aspect of diagnosis of depression is to rule
out bipolar disorder. Many patients with bipolar disorder
present to the clinicians during the depressive phase of
illness and spontaneously do not report about previous
hypomanic or manic episodes. Careful history from the
patient and other sources (family members) often provide
important clues for the bipolar disorder. It is often useful to
use standardized scales like mood disorder questionnaire to
rule out bipolarity. Treating a patient of bipolar depression
as unipolar disorder can increase the risk of antidepressant
Area to be covered in assessment include symptom
dimensions, symptom-severity, comorbid psychiatric and
medical conditions, particularly comorbid substance abuse,
the risk of harm to self or others, level of functioning and
the socio-cultural milieu of the patient.
In case patient has received treatment in the past, it is
important to evaluate the information in the form of type of
antidepressant used, dose of medication used, compliance
with medication, reasons for poor compliance, reasons for

Patient with Depressive features

Consider differential diagnoses like

• Organic Depression, medication induced depression,
substance induced depression, premenstrual dysphoric
disorder
• Rule out bipolar disorder

Establish the diagnosis of Depression

Assessment
• Severity of illness
• Risk of harm to self and others- current suicidal ideations, suicidal attempts;
past history of non-suicidal self-harm behaviour, past history of suicidal attempts,
severity of attempt
• Comorbid substance use/dependence
• Personality factors
• Level of functioning- work dysfunction
• Detailed Physical examination- thyroid swelling, evidence for nutritional deficiency,
and physical illness which could contribute to depression
• Record- blood pressure, weight and wherever indicated body mass index and waist
circumference
• Mental Status Examination
• Investigations- haemogram, liver function test, renal function test, fasting blood glucose level,
thyroid function test (if required), Urine pregnancy test (if required)
• Treatment history- response to previous medication trials, compliance, side effects, etc.
• Patient’s and caregivers beliefs about the cause of illness and beliefs about the treatment
• Assessment for social support, stigma, coping
• Assessment of caregiver burden, coping and distress

• Decide about treatment setting- consider inpatient care in case of suicidality, malnutrition,
catatonia, comorbid general medical conditions making management difficult at the
outpatient setting
• Liaison with other specialists depending on the need of the patient

Pharmacological Management Electroconvulsive therapy Non-Pharmacological

• Choose an antidepressant based on past • Catatonia, suicidality, Management
treatment response, past history of side severe depression, past • Psychoeducation
effects, cost, comorbidity, patient/family response to ECT, • Psychotherapeutic
preference, availability augmentation etc. intervention

Figure 1: Initial evaluation and management plan for Depression

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discontinuation of medication, response to treatment, side
effects experienced etc. If the medications were changed,
then the reason for change is also to be evaluated.
Wherever possible, unstructured assessments need to be
supplemented by ratings on appropriate standardized
rating scales. Depending on the need, investigations
need to be carried out. The use of neuroimaging may be
indicated in those with first-episode of depression seen in
late or very late age; those have neurological signs, those
having treatment resistant depression.
Besides, patients, information about the illness need to be
obtained from the caregivers too and their knowledge and
understanding of the illness, their attitudes and beliefs
regarding treatment, the impact of the illness on them and
their personal and social resources need to be evaluated.
FORMULATING A TREATMENT PLAN (FIGURE-1)
Formulation of treatment plan involves deciding about
treatment setting, medications and psychological treatments
to be used. Patients and caregivers may be actively consulted
while preparing the treatment plan. A practical, feasible and
flexible treatment plan can be formulated to address the needs
of the patients and caregivers. Further the treatment plan can
be continuously re-evaluated and modified as required.
EVALUATE THE SAFETY OF PATIENT AND
OTHERS
A careful assessment of the patient’s risk for suicide should
be done. During history inquiry for the presence of suicidal
ideation and other associated factors like presence of
psychotic symptoms, severe anxiety, panic attacks and
alcohol or substance abuse which increases the risk of suicide
need to be evaluated. It has been found that severity of
depressive symptomatology is a strong predictor of suicidal
ideation over time in elderly patients. Evaluation also includes
history of past suicide attempts including the nature of those
attempts. Patients also need to be asked about suicide in their
family history. During the mental status examinations besides
enquiring about the suicidal ideations, it is also important to
enquire about the degree to which the patient intends to act
on the suicidal ideation and the extent to which the patient has
made plans or begun to prepare for suicide. The availability
of means for suicide be inquired about and a judgment may
be made concerning the lethality of those means. Patients
who are found to possess suicidal or homicidal ideation,
intention or plans require close monitoring. Measures such as
hospitalization may be considered for those at significant risk.
CHOICE OF TREATMENT SETTINGS
Majority of the cases of depression seen in the clinical
setting are of mild to moderate severity and can be managed
Indian J Psychiatry 59 (Supplement 1), January 2017
at the outpatient setting. However, some patients have
severe depression which may be further associated with
psychotic symptoms, catatonic symptoms, poor physical
health status, suicidal or homicidal behaviour etc. In such
cases, careful evaluation is to be done to decide about the
treatment setting and whenever necessary inpatient care
may be offered. In general, the rule of thumb is that the
patients may be treated in the setting that is most safe and
effective. Severely ill patients who lack adequate social
support outside of a hospital setting may be considered
for admission to a hospital whenever feasible. The optimal
treatment setting and the patient’s ability to benefit
from a different level of care may be re-evaluated on an
ongoing basis throughout the course of treatment. Some
of the common indications for inpatient care are shown
in Table-4.
Table 4: Some indications for inpatient care during
acute episodes
• Presence of suicidal behaviour which puts the life of the patient at risk
• Refusal to eat which puts the life of patient at risk
• Severe malnutrition
• Catatonia
• Presence of general medical or comorbid psychiatric conditions that make
outpatient treatment unsafe or ineffective
All inpatients should have accompanying family caregivers.
In case inpatient care facilities are not available, than the
patient and/or family need to be informed about such a
need and admission in nearest available inpatient facility
can be facilitated.
THERAPEUTIC ALLIANCE
Irrespective of the treatment modalities selected for
patients, it is important for the psychiatrist to establish a
therapeutic alliance with the patient. A strong treatment
alliance between patient and psychiatrist is crucial for poorly
motivated, pessimistic depressed patient who are sensitive
to side effect of medications. A positive therapeutic alliance
always generates hope for good outcome.
ENHANCED TREATMENT COMPLIANCE
The successful treatment of major depressive disorder
requires adequate compliance to treatment plan. Patients
with depressive disorder may be poorly motivated and
unduly pessimistic over their chances of recovery with
treatment. In addition, the side effect or requirements of
treatment may lead to non-adherence. Patients are to be
encouraged to articulate any concern regarding adherence
and clinicians need to emphasize the importance of
adherence for successful treatment. Simple measures
which can help in improving the compliance are given in
table-5.
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ADDRESS EARLY SIGNS OF RELAPSE
Many patients with depression experience relapse.
Accordingly, patients as well as their families if appropriate may
Table 5: Measures which can improve medication
compliance
• When and how often to take medicines
• Preferably give once a day dosing
• Prescribe minimum number of tablets
• Always ask the patient about kind of formulation (e.g. tablet, capsule etc)
which they would prefer to take
• Check the whole prescription to avoid duplication of medication
• Explain the patient that the beneficial effect will be seen only after
2‑4 weeks of intake of medications
• Explain the patient the need to take medication even after feeling better
• Explanation of side effects, If patients asks about the side effects‑ explain
the patient about the same
• Explain the patient as to what to do‑ if they encounter side effects
• Encourage the patient to report side effects
• The need to consult with psychiatrist before discontinuing medications
be educated about the risk of relapse. They can be educated
to identify early signs and symptoms of new episodes. Patients
can also be asked to seek adequate treatment as early in the
course of a new episode as possible to decrease the likelihood
of a full-blown relapse or complication.
TREATMENT OPTIONS FOR MANAGEMENT
FOR DEPRESSION
Treatment options for management of depression can be
broadly be divided into antidepressants, electroconvulsive
therapy (ECT) and psychosocial interventions. Other less
commonly used treatment or treatments used in patients
with treatment resistant depression include repetitive
transcranial magnetic stimulation (rTMS), light therapy,
transcranial direct stimulation, vagal nerve stimulation,
deep brain stimulation and sleep deprivation treatment.
In many cases benzodiazepines are used as adjunctive
treatment, especially during the initial phase of treatment.

Table 6: Antidepressants Armamentarium

Antidepressant Usual dose range (mg/day) Common side effects
Selective serotonin reuptake inhibitors (SSRI)
Fluoxetine 20‑80 Sexual dysfunction, GI distress, weight loss/gain,
Paroxetine 20‑60 anxiety, insomnia
Fluvoxamine 50‑300
Sertraline 50‑200
Citalopram 20‑40
Escitalopram 10‑20
Tricyclic tertiary amines (TCAs)
Amitriptyline 50‑200 Sexual dysfunction, anticholinergic effects, drowsiness,
Doxepin 75‑300 orthostasis, conduction abnormalities, mild GI distress,
Imipramine 75‑300 weight gain
Clomipramine 75‑300
Tricyclic Secondary Amines
Desipramine 100‑300
Nortriptyline 25‑150
Protriptyline 15‑20
Tetracyclic
Maprotiline 50‑75
Unicyclic
Bupropion 150‑450 Mild GI distress, high risk of seizure after 450 mg/day
Norepinephrine Serotonin reuptake
Inhibitors (NSRI)
Venlafaxine 75‑300 Mild anticholinergics effects, drowsiness, conduction
Duloxetine 20‑60 abnormalities, GI distress
Milnacipran 50‑200
Desvenlafaxine
Norepinephrine Serotonin Reuptake
Enhance (NSRE)
Tianeptine 25‑50 Nausea, constipation, abdominal pain, headache,
dizziness and changes in dreaming
Noradrenaline and Specific Serotonin
Antidepressants (NaSSA)
Mirtazapine 15‑45 Mild anticholinergic effects, drowsiness, orthostasis,
conduction abnormalities, GI distress, weight gain
Atypical antidepressants/Serotonin
Modulators
Trazadone 150‑300 Mild anticholinergic effects, drowsiness, orthostasis,
Nefazodone 100‑300 conduction abnormalities, GI distress, weight gain,
severe hepatotoxicity
Contd...
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Gautam, et al.: CPGs for depression
Table 6: Contd...
Antidepressant Usual dose range (mg/day)
Reversible Selective Mono Amine Oxidase
Inhibitors (RIMA)
Moclobemide
Mono Amine Oxidase Inhibitors (MAOI)
Phenelzine
Isocarboxazid
Tranylcypromine
Serotonin partial agonist reuptake
inhibitor (SPARI)
Vilazodone
Table 7: Factors that determine the selection of
Antidepressant Drug
Patient specific
• Patients preference
• Previous history of response/tolerability to medication in the patient or
family member
• Past side effects with medication
• Other medication being taken – drug interactions
• Patient’s age – with increasing age the pharmacokinetic and
pharmacodynamic changes become more important
• Comorbid medical illness (e.g., glaucoma, cardiac conditions)
• Comorbid psychiatric disorder/symptoms
• Gender issues – sexual dysfunction
• Intellectual and psychological capacities
Drug specific
• Side effects
• Cost
• Dosing strategy
• Type of formulation ‑ Tablet, Cap, Syrup
• Safety in overdose (Relative Toxicity) ‑ fatal overdose is significantly
• Lower with SSRIs than with tricyclic antidepressants
Additionally in some cases, lithium and thyroid supplements
may be used as an augmenting agent when patient is not
responding to antidepressants.
Antidepressants
Large numbers of antidepressants (Table-6) are available for
management of depression and in general all the antidepressants
have been shown to have nearly equal efficacy in the management
of depression. Antidepressant medication may be used as
initial treatment modality for patients with mild, moderate,
or severe depressive episode. The selection of antidepressant
medications may be based on patient specific and drug specific
factors, as given in Table-7. In general, because of the side
effect and safety profile, selective serotonin reuptake inhibitors
(SSRIs) are considered to be the first line antidepressants. Other
preferred options include tricyclic antidepressants, mirtazapine,
bupropion, and venlafaxine. Usually the medication must be
started in the lower doses and the doses must be titrated,
depending on the response and the side effects experienced.
Dose and duration of antidepressants
Patients who have started taking an antidepressant
medication should be carefully monitored to assess the
Indian J Psychiatry 59 (Supplement 1), January 2017
Common side effects
45‑90 Orthostatic hypotension, drowsiness,
30‑60 insomnia, headaches
20‑60
20‑40 Diarrhea, nausea or vomiting, and insomnia
response to pharmacotherapy as well as the emergence of
side effects and safety. Factors to consider when determining
the frequency of monitoring include severity of illness,
patient’s co-operation with treatment, the availability of
social support and the presence of comorbid general medical
problems. Visits may be kept frequent enough to monitor
and address suicidality and to promote treatment adherence.
Improvement with pharmacotherapy can be observed after
4-6 weeks of treatment. If at least a moderate improvement is
not observed in this time period, reappraisal and adjustment
of the pharmacotherapy should be considered.
Psychotherapeutic interventions
A specific, effective psychotherapy may be considered
as an initial treatment modality for patients with mild to
moderate depressive disorder. Clinical features that may
suggest the use of a specific psychotherapy include the
presence of significant psychosocial stressors, intrapsychic
conflict and interpersonal difficulties. Patient’s preference
for psychotherapeutic approaches is an important
factor that may be considered in the decision to use
psychotherapy as the initial treatment modality. Pregnancy,
lactation, orthe wish to become pregnant may also be an
indication for psychotherapy as an initial treatment. Various
psychotherapeutic interventions which may be considered
based on feasibility, expertise available and affordability are
shown in Table-8.
Cognitive behavioral therapy (CBT) and interpersonal
therapy are the psychotherapeutic approaches that have the
best documented efficacy in the literature for management
of depression. When psychodynamic psychotherapy is used
as specific treatment, in addition to symptom relief it is
frequently with broader long term goals.
The psychiatrist should take into account multiple
factors when determining the frequency of sessions for
individual patients, including the specific type and goals
of psychotherapy, the frequency necessary to create and
maintain a therapeutic relationship, the frequency of visits
required to ensure treatment adherence, and the frequency
necessary to monitor and address suicidality. The frequency
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of outpatient visits during the acute phase generally varies
from once a week in routine cases to as often as several
times a week. Regardless of the type of psychotherapy
selected, the patient’s response to treatment should be
carefully monitored. For a given patient, time spent and
frequency of visit may be decided by the psychiatrist.
Psychoeducation to the patient and, when appropriate, to
the family
Education concerning depression and its treatments can
be provided to all patients. When appropriate, education
can also be provided to involved family members. Specific
educational elements may be helpful in some circumstances,
e.g. that depression is a real illness and that effective
treatments are both necessary and available may be crucial
for patients who attribute their illness to a moral defect
or witch craft. Education regarding available treatment
options will help patients make informed decisions,
anticipate side effects and adhere to treatments. Another
important aspect of providing education is informing the
patient and especially family about the lag period of onset
of action of antidepressants. Important components of
psychoeducation are given in Table-9.
Combination of pharmacotherapy and Psychotherapy
There is class of patients who may require the combination
of pharmacotherapy and psychotherapy. In general, the
same issues that influence the choice of medication or
psychotherapy when used alone should be considered
when choosing treatments for patients receiving combined
therapy.
PHASES OF ILLNESS/TREATMENT
Management of depression can be broadly divided into three
phases, i.e., acute phase, continuation phase and maintenance
phase. Maintenance phase of treatment is usually considered
when patient has recurrent depressive disorder.
ACUTE PHASE TREATMENT
The goal of acute phase treatment is to achieve remission,
as presence of residual symptoms increase the risk of
chronic depression, poor quality of life and also impairs
recovery from physical illness. Treatment generally results
in improvement in quality of life and better functional
capacity. The various components of acute phase treatment
are shown in Table-10 and the treatment algorithm is shown
in figure-2 and 3.
In acute phase psychiatrist may choose between
several initial treatment modalities, including
pharmacotherapy, psychotherapy, the combination of
medication and psychotherapy, or ECT. Selection of an
initial treatment modality is usually influenced by both
clinical (e.g. severity of symptoms) and other factors
(e.g. patient preference).
Antidepressant medication may be used as initial treatment
modality for patients with mild, moderate, or severe major
depressive disorder. Clinical features that may suggest that
medication are the preferred treatment modality includes
history of prior positive response to antidepressant
medication, severity of symptoms, significant sleep and
appetite disturbance, agitation, or anticipation of the need
for maintenance therapy. Patients with severe depression
with psychotic features will require use of combination of
antidepressant and antipsychotic medication and/or ECT.
The initial selection of an antidepressant medication is
largely be based on the anticipated side effects, the safety
or tolerability of these side effects for individual patients,
patient preference and comorbid physical illnesses.
Dose and duration of antidepressants: Once an
antidepressant medication has been selected, it can be
started initially at lower doses and careful monitoring to

Table 8: Psychotherapeutic interventions for Depression

Type of therapy
Cognitive Behaviour Therapy (CBT) • Identifying problems, Identifying cognitive distortions/errors, generating alternative thoughts,
problem solving, mastery and pleasure rating, activity scheduling, anxiety management
strategies‑ relaxation exercises
Interpersonal Therapy (IPT) • Focuses on losses, role disputes and transitions, social isolation, deficits in social skills, and other
interpersonal factor that may impact on the development of depression
Supportive psychotherapy • Allowing the patient to ventilate, providing emotional support, guidance, increasing the patient’s
self‑esteem, accepting feelings at face value, enhancing hope, enhancing adaptive coping
Behavioral Therapy (BT) • Activity scheduling, social skills training and problem solving
Marital Therapy (MT) • Marital therapy conceptualizes depression as an interpersonal context such that both members of
the marital dyad are included in therapy. Treatment includes behavioral exchange, communication
training, problem solving, and resolution of conflict around issues such as financial, sex, affection,
parenting, and intimacy
Family Therapy • When interpersonal problems in the context of pathological family dynamics are responsible for
depression, than family therapy may be considered. It would involve all the family members and
include similar principles as for marital therapy
Brief Psychodynamic Psychotherapy (BPD) • The premise of brief psychodynamic psychotherapy is that depressive symptoms remit as patient
learns new methods to cope with inner conflicts. Several different approaches have been described

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Mild to moderate Depression

Evaluate for the type and severity of depression

Evaluate for past history of depression
Evaluate for past history of treatment and response
Evaluate for family history of depression
Evaluate for physical and psychiatric comorbidity
Evaluate for concomitant drugs which patient is receiving
Evaluate for the presence of psychosocial stressors

Patient’s preference
No past history of depression
Mild to moderate depression Patient’s preference
Presence of psychosocial stressors Past and family history of
Past history of good response good response
Receiving other medications and high Low risk of drug interactions
risk of drug interactions Moderate depression

Psychotherapy Pharmacotherapy Remission

Remission

No response Partial response No response

Optimize the treatment Change antidepressant

Change to • Increase the frequency of psychotherapy or
antidepressant • Increase the dose of antidepressants to Switch to psychotherapy
maximum tolerable dose

Change/Combination
• If receiving psychotherapy – add antidepressants
• If receiving antidepressants – add psychotherapy or change the antidepressant

Augmentation/Combination
• If receiving antidepressants – add second antidepressants/
augmenting agent taking into consideration the issue of tolerability
and side effects

Figure -2: Treatment algorithm of mild to moderate Depression

Table 9: Basic components of Psychoeducation be done to assess the response to pharmacotherapy as

• Assessing the knowledge of the patient and caregivers about aetiology,
treatment and prognosis
• Explain about the diagnosis and symptoms of depression
• Explain that depression is a medical disorder which is treatable
• Explain about the lag period of onset of action
• Provide information about aetiology
• Provide information about treatment in terms of available options, their
efficacy/effectiveness, side effects, duration of use
• Discuss about importance of medication and treatment compliance
• Provide information about possible course and long term outcome
• Discuss about problems of substance abuse, interpersonal conflict, stress etc
• Discuss about how to deal with day today stress
• Discuss about communication patterns, problem solving etc
• Enhancing adaptive coping to deal with persistent/residual symptoms
• Discuss about relapse and how to identify the early signs of relapse
• Encourage healthy life styles
Indian J Psychiatry 59 (Supplement 1), January 2017
well as the emergence of side effects, clinical conditions,
and safety. Factors to consider when determining the
frequency of monitoring include severity of illness, patient’s
cooperation and presence with treatment, and availability
of social support andpresence of comorbid general medical
problems. Visits may be frequent enough to monitor and
address suicidality and to promote treatment adherence.
Improvement with pharmacotherapy can be observed after
4-6 weeks of treatment. If at least a moderate improvement
is not observed in this time period, reappraisal and
adjustment of the pharmacotherapy maybe considered.
In the initial phase, depending on the symptom severity and
type of symptoms, such as presence of insomnia or anxiety,
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Severe Depression

Evaluate for past history of depression

Evaluate for past history of treatment and response
Evaluate for family history of depression
Evaluate for physical comorbidity
Evaluate for concomitant drugs which patient is receiving
Evaluate for the presence of psychosocial stressors
Evaluate the cognitive functions
Evaluate for suicidality, oral intake

Patient’s preference
Past history of good response Patient’s preference
Receiving other medications Past and family history of good response
and high risk of drug interactions Low risk of drug interactions
Suicidal
Poor oral intake
Catatonic symptoms

Pharmacotherapy

ECT+ Pharmacotherapy
(ECT for treatment of acute disturbance and
antidepressants for the continuation phase)
Partial response

No response

Optimize the treatment

• Increase the dose of antidepressants to
maximum tolerable dose

No further response

 Switch to an antidepressant from same or different

pharmacological class or dual acting agent
 Add ECT
 Add second antidepressants/ augmenting agent
taking into consideration the issue of tolerability
and side effects

Figure 3: Treatment algorithm of Severe Depression

Table 10: Management in the acute phase
• Comprehensive assessment (psychiatric/medical/psychosocial)
• Deciding on goals of treatment
Achieving remission
Ensure safety of patient and others
• Choice of treatment setting
• Choosing a treatment modality: antidepressant medication, psychotherapy,
combined treatment with antidepressant and psychotherapy
• Use of adjunctive medications when indicated
• Use of ECT when indicated
• Psychoeducation
benzodiazepines or other hypnotics may be used for short
duration.
Failure to response: If at least some improvement (>25%)
is not observed following 4 week of pharmacotherapy, a
reappraisal of the treatment regimen be conducted and
a change in antidepressant may be considered. When
patient shows 25-50% improvement during the initial 4
weeks of antidepressant trial, the dose must be optimized
to the maximum tolerable dose. If there is less than 50%
improvement with 6-8 weeks of maximum tolerable dose
and the medication compliance is good, a change in
antidepressant may be considered.
If after 4-8 weeks of treatment, if a moderate improvement is
not observed, then a thorough review and reappraisal of the
diagnosis, complicating conditions and issues, and treatment
plan may be conducted. Reappraisal of the treatment
regimen may also include evaluation of patient adherence and
pharmacokinetic/pharmacodynamic factors. Following this
review, the treatment plan can be revised by implementing one
of several therapeutic options, including maximizing the initial
medication treatment, switching to another antidepressant
medication, augmenting antidepressant medications with
other agents/psychotherapy/ECT. Maximizing the initial

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Continuation Phase treatment

Treated with Treated with Treated with combination Treated with combination
antidepressants psychotherapy of psychotherapy and of antidepressants and
during the acute during the acute antidepressants during the ECT/antipsychotics during
phase phase acute phase the acute phase

Continue antidepressants Continue psychotherapy at Continue with Continue with

at the same dose for 6- the same or decreased antidepressants at the antidepressants and
9month after achieving frequency for 6-9 months same dose and antipsychotic at the same
remission after achieving remission psychotherapy at the dose and for 6-9 months
same or decreased after achieving
frequency for 6-9 remission
months after achieving
remission

Monitor for relapse of symptoms

No past H/O depression Past H/O depression

Discontinue treatment depression treatment Maintenance Treatment

Figure 4: Treatment algorithm for continuation phase treatment of depression

Maintenance Phase treatment

(H/O of ≥ 3 episodes)

• Treated with antidepressants during the acute • Treated with • Treated with
and continuation phase psychotherapy during antidepressants and
• Treated with combination of antidepressants the acute and psychotherapy during
and ECT/ antipsychotics during the acute continuation phase the acute and
and continuation phase continuation phase

• Continue with same treatment preferably for life long

• Monitor symptoms and treatment tolerability

Figure 5: Treatment algorithm for maintenance phase of depression

treatment regimen is perhaps the most conservative strategy. SSRI to another SSRI) or to one from a different pharmacologic
While using the higher therapeutic doses, patients are to be class (e.g., from an SSRI to a tricyclic antidepressant). Some
closely monitored for an increase in the severity of side effects expert suggests that while switching, a drug with a different
or emergence of newer side effects. or broader mechanism of action may be chosen.

Switching to a different antidepressant medication is a Augmentation of antidepressant medications may be helpful,

common strategy for treatment-refractory patients, especially
those who have not shown at least partial response to the
initial medication regimen. There is no consensus about
switching and patients can be switched to an antidepressant
medication from the same pharmacologic class (e.g., from an
particularly for patients who have had a partial response
to initial antidepressant monotherapy. Options include
adding a second antidepressant medication from a different
pharmacologic class, or adding another adjunctive medication
such as lithium, psychostimulants, modafinil, thyroid hormone,

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an anticonvulsant etc. Adding, changing, or increasing the
intensity of psychotherapy may be considered for patients
who do not respond to medication treatment. Following any
change in treatment, close monitoring need to be done. If at
least a moderate level of improvement in depressive symptoms
is not seen after an additional 4–8 weeks of treatment, another
thorough review need to be done. This reappraisal may include
verifying the patient’s diagnosis and adherence; identifying and
addressing clinical factors that may be preventing improvement,
such as the presence of comorbid general medical conditions
or psychiatric conditions (e.g., alcohol or substance abuse);
and identifying and addressing psychosocial issues that may
be impeding recovery. If no new information is uncovered to
explain the patient’s lack of adequate response, depending on
the severity of depression, ECT maybe considered.
Choice of a specific psychotherapy: Out of the various
psychotherapeutic interventions used for management
of depression, there is robust level of evidence for use of
CBT. The major determinants of type of psychotherapy
are patient preference and the availability of clinicians
with appropriate training and expertise in specific
psychotherapeutic approaches. Other clinical factors which
will influence the type of psychotherapy include the severity
of the depression. Psychotherapy is usually recommended
for patients with depression who are experiencing stressful
life events, interpersonal conflicts, family conflicts, poor
social support and comorbid personality issues.
The optimal frequency of psychotherapy may be based on
specific type and goals of the psychotherapy, the frequency
necessary to create and maintain a therapeutic relationship,
the frequency of visits required to ensure treatment
adherence, and the frequency necessary to monitor and
address suicidality. Other factors which would also determine
the frequency of psychotherapy visits include the severity
of illness, the patient’s cooperation with treatment, the
availability of social supports, cost, geographic accessibility,
and presence of comorbid general medical problems.
Besides the use of specific psychotherapy, all patients and their
caregivers may receive psychoeducation about the illness.
Role of Yoga and Meditation in management of
depression: Studies related to role of traditional therapies
like meditation, Yoga and other techniques have been
mostly published in documents of various organizations
propagating that particular technique. Well-designed
scientific studies to authenticate these claims need to
be conducted; however, efficacy of these techniques as
supportive/adjuctive therapy is widely accepted.
TREATMENT IN CONTINUATION PHASE
The goal of continuation phase is to maintain the gains
achieved in the acute phase of treatment and prevent relapse
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of symptoms. The treatment algorithm to be followed is
shown in figure-4. Patients who have been treated with
antidepressants in the acute phase need to be maintained on
same dose of these agents for 16-24 weeks to prevent relapse
(total period of 6-9 month from initiation of treatment). There
are evidences to support the use of specific psychotherapy
in continuation phase to prevent relapse. The use of other
somatic modalities (e.g. ECT) may be useful in patients where
pharmacology and/or psychotherapy have failed to maintain
stability in continuation phase. The frequency of visit during
the continuation phase may be determined by patient’s clinical
condition as well as the specific treatment being provided. If
maintenance phase treatment is not indicated for patients who
remain stable following the continuation phase, patients may
be considered for discontinuation of treatment. If treatment
is discontinued, careful monitoring be done for relapse, and
treatment to be promptly reinstituted if relapse occurs.
TREATMENT IN MAINTENENCE PHASE
The goal of maintenance phase treatment is to prevent recurrence
of depressive episodes. On an average, 50-85% of patients with
a single episode of major depression have at least one more
episodes. Therefore, maintenance phase treatment may be
considered to prevent recurrence. The duration of treatment
may be decided keeping in view the previous treatment history
and number of depressive episodes the person has had in the
past. Mostly the treatment that was effective for acute and
continuation phase need to be used in the maintenance phase
(Figure-5). Same doses of antidepressants, to which the patient
had responded in previous phase is considered. The frequency
of visit for CBT and IPTcan be reduced during the maintenance
phase (once a month). There is no consensus regarding the
duration and when to give and when not to give maintenance
treatment. There is agreement to large extent that patients
who have history of three or more relapses or recurrences need
to be given long-term treatment.
DISCONTINUATION OF TREATMENT
The decision to discontinue maintenance treatment may
be based on the same factors considered in the decision to
initiate maintenance treatment, including the probability
of recurrence, the frequency and severity of past episodes,
the persistence of depressive symptoms after recovery, the
presence of comorbid disorders, and patient preferences.
When the decision is made to discontinue or terminate
psychotherapy in the maintenance phase, the manner in
which this is done may be individualized to the patient’s
needs. When the decision is made to discontinue maintenance
pharmacotherapy, it is best to taper the medication over
the course of at least several weeks to few months. Such
tapering may allow for the detection of emerging symptoms
or recurrences when patients are still partially treated and
therefore can be easily returned to full therapeutic intensity.
In addition, such tapering can help minimize the risks of
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Special situation
Suicidal risk
Psychotic features
Atypical features
Alcohol and/or substance
abuse or dependence
Depression with features of
obsessive‑compulsive disorder
Depression with panic and/or
other anxiety disorders
Depression with cognitive
dysfunction (pseudo
dementia)
Dementia
Post Psychotic Depression
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Gautam, et al.: CPGs for depression
Table 11: Management of depression Special situations
Strategies
• Risk of suicide is high in patients with depression.
• Suicide risk to be assessed initially and over the course of treatment.
• If the patient has suicidal ideation, intention, and/or a plan, close surveillance is necessary.
• Whenever possible, information about presence of suicidal ideation in patient be shared with family members and
they need to be instructed for various safety measures to be taken.
• The risk of suicide in some patients recovering from depression increases transiently as they develop the energy
and capacity to act on self‑destructive plans made earlier in the course of their illness. However, it is not possible
to predict with certainly whether a given patient will kill himself or herself.
• A careful selection of antidepressants and ECT is an important decision to be taken by psychiatrist after
considering all related factors.
• Wherever feasible, the prescribed drugs need not be in the possession or reach of patient having suicidal intention.
• Depression with psychotic features carries a higher risk of suicide than does major depression uncomplicated by
psychosis
• It also constitutes a risk factor for recurrent depression.
• Depression with psychotic features responds better to treatment with a combination of antidepressants and
antipsychotics than to treatment with either component alone.
• ECT is also highly effective in depression with psychotic features.
• Atypical depressive feature include severe anxiety, vegetative symptoms of reversed biological functions (i.e.,
increased rather than decreased sleep, appetite, and weight), marked mood reactivity, sensitivity to emotional
rejection, phobic symptoms, and a sense of severe fatigue that creates a sensation of “leaden paralysis” or extreme
heaviness of the arms or legs.
• Tricyclic antidepressants yield response rates of only 35%‑50%. Response rates with MAO inhibitors are in
the range of 55%‑75% in patients with atypical depression. If it is determined that the patient does not wish to,
cannot, or is unlikely to adhere to the dietary and drug precautions associated with MAO inhibitor treatment, the
use of an alternative antidepressant is indicated.
• The results of several studies suggest that SSRIs, MAOIs, and possibly bupropion maybe more effective
treatment for atypical depression.
• Because of the frequent comorbidity of depression and alcohol or other substance abuse, efforts need to be made
to obtain a detailed history of the patient’s substance use.
• If the patient is found to have a substance use disorder, a program to ensure abstinence may be regarded as a
principle priority in the treatment.
• It is also advisable, if other factors permit, to detoxify such a patient before initiating antidepressant therapy.
• Benzodiazepines and other sedative hypnotics carry the potential for abuse or dependence and these may be used
cautiously except as part of a detoxification regimen.
• Hepatic dysfunction and hepatic enzyme induction frequently complicate pharmacotherapy of patients with
alcoholism and other substance abuse; these conditions require careful monitoring of blood levels.
• Clomipramine and the SSRIs have been demonstrated to be efficacious in the management of
obsessive‑compulsive symptoms in addition to their antidepressants efficacy.
• Panic disorder complicates major depression in 15%‑30% of the cases.
• TCAs and SSRIs may initially worsen, rather than alleviating anxiety and panic symptoms; these medications
may therefore be introduced at a low dose and slowly increased when used to treat such patients.
• High potency benzodiazepine like alprazolam and clonazepam may sometimes be used with benefit either in
combination with antidepressants or as the sole pharmacological agent for anxiety, with or without panic, coupled
with milder forms of depression.
• Signs and symptoms of cognitive inefficiency routinely accompany major depression.
• Some patients have both depression and dementia, while others have depression that causes cognitive
impairment (i.e., pseudo‑dementia).
• Several clinical features help in differentiating pseudo‑dementia from true dementia. Pseudo‑demented patients
generally exert relatively less effort but report more incapacity than patients with true dementia. In more
advanced stage, patients with dementia typically fail to recognize their cognitive failure.
• It is important that patients with major depression with cognitive disturbance are not misdiagnosed and thereby
denied the antidepressant medication or ECT.
• Depression related cognitive dysfunction is a reversible condition that resolves with treatment of the underlying
depression.
• Individuals suffering from dementia need to be prescribed antidepressants which have least potential of
anticholinergic effect, e.g., bupropion, fluoxetine, sertraline, and, of the tricyclic agents, desipramine or
nortriptyline. Alternatively, some patients do well when given stimulants in small doses.
• Among SSRIs, paroxetine may be avoided.
• ECT is also effective in depression superimposed on dementia, and it may be used if medications are
contraindicated, not tolerated, or if immediate resolution of the major depressive disorder episode is medically
indicated (such as when it interferes with the patient’s acceptance of food).
• Adding an antidepressant agent to the patient’s antipsychotic regimen can help in managing post‑psychotic
depression effectively.
Contd...
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Special situation
Depression during pregnancy
or following Childbirth
Seasonal depression
Depression in elderly
Depression in Children
Post‑ Stroke Depression
Cardiac disease:
Hypertension
S46
Gautam, et al.: CPGs for depression
Table 11: Contd...
Strategies
• Women in childbearing age may be counseled about the risk of becoming pregnant while taking psychotropic
medications.
• Whenever possible, a pregnancy is to be planned in consultation with psychiatrist so that medication may be
discontinued before conception if feasible.
• The clinicians need to carefully weigh the risks and benefits of prescribing psychotropic agents to the pregnant
patient, taking into consideration the possibilities of physical (especially during the first trimester) and behavioral
teratogenesis.
• In patients whose safety and well‑being require antidepressants medications, antidepressants may be justifiably
used, after the first trimester, if possible.
• ECT may be used as an alternative treatment; the current literature supports the safety for mother and fetus, as
well as the effectiveness of ECT during pregnancy.
• Postpartum depression is to be treated according to the same principles delineated for other depressive condition.
• However, issue of breast feeding and appropriate precautions need to be explained to patient and caregivers.
• Some individuals suffer annual episode of depression whose onset is in the fall or early winter, usually at the
same time each year.
• The depressive episodes frequently have atypical features such as hypersomnia and overeating.
• The entire range of treatments for depression may also be used to treat seasonal affective disorder, either in
combination with or as an alternative to light therapy.
• Antidepressants are effective in treatment of depression in old age.
• The high rates of adverse effects associated with TCAs suggest that these agents must not be used as the first line
agents.
• The lower rate of adverse events in the newer antidepressants (SSRIs) makes them more acceptable. However,
nortriptyline has a role in severe depression in the elderly.
• ECT has demonstrated efficacy in treatment of old age depression with the benefit of rapid response in the
severely ill with and without psychotic symptoms.
• There are evidences that SSRIs are effective in child and adolescent depression and these are generally the first
choice of drug.
• The commonly used SSRIs include fluoxetine. Other newer antidepressants have not been adequately evaluated
in childhood and use of all these classes of drugs may be used with careful monitoring.
• Psychotherapeutic interventions like CBT and IPT have also been shown to be efficacious in children and
adolescents.
• Post Stroke Depression is a common problem seen in at least 30‑40% of survivors of intra‑cerebral hemorrhage.
• Antidepressant drugs may be beneficial in managing depressive symptoms and allow faster Post Stroke
rehabilitation.
• Treatment is complicated by medical co‑morbidity and by the potential for interaction with other co‑prescribed
drugs.
• Fluoxetine and nortriptyline are probably the most standard and seen to be effective.
• The presence of specific cardiac conditions complicates or contraindicates certain forms of antidepressant
medication therapy, notably use of TCAs.
• Cardiac history is to be carefully explored before the initiation of medication treatment. Although TCAs have
been used effectively to treat depression in patients with some forms of ischemic heart disease, particular care
need to be taken in using TCAs in patients with a history of ventricular arrhythmia, subclinical sinus node
dysfunction, conduction defects (including asymptomatic conduction defects), prolonged QT intervals, or a recent
history of myocardial infarction.
• SSRIs, bupropion, and ECT appear to be safer for patients with preexisting cardiac disease, although the latter
may require consultation with a specialist and treatment modification before use. However, there are also reports
which suggest that SSRIs can also lead to arrhythmia.
• MAOIs do not adversely affect cardiac conduction, rhythm, or contraction but may induce orthostatic
hypotension and also run the risk of interacting adversely with other medications that may be taken by such
patients. There is anecdotal evidence that trazodone may induce ventricular arrhythmias, but this agent may be
avoided in elderly because of orthostatic blood pressure decrements.
• Consultation with the patient’s cardiologist before and during antidepressant medication treatment may be advisable
and is especially advisable during any treatment for a patient who has recently had a myocardial infarction.
• Antihypertensive agents and TCAs may interact to either intensify or counteract the effect of the antihypertensive therapy.
• The action of antihypertensive agents that block alpha receptors (e.g., prazosin) may be intensified by
antidepressant medications that block these same receptors, notably the TCAs and trazodone. TCAs may
antagonize the therapeutic actions of guanethidine, clonidine, or α‑methyldopa.
• Antihypertensive, like diuretics which mainly act on kidney, may precipitate SIADH, when given along with
SSRIs.
• Concurrent antihypertensive treatment, especially with diuretics, increases the likelihood that TCAs, trazodone,
or MAOIs will induce symptomatic orthostatic hypotension.
• β Blockers, especially propranolol, may be a cause of depressive disorder in some patients.
• Dose‑dependent elevations in blood pressure with venlafaxine are usually mild, although more severe elevations
have been observed, making this agent less preferable in patients with hypertension.
Contd...
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Gautam, et al.: CPGs for depression

Table 11: Contd...
Special situation Strategies
Diabetes mellitus • SSRIs may reduce serum glucose by up to 30% and cause appetite suppression, resulting in weight loss.
• Fluoxetine may be avoided, owing to its increased potential for hypoglycaemia, particularly in patients with
non‑insulin dependent diabetes. If fluoxetine is prescribed, the patient should be advised of the need to monitor
serum glucose levels regularly.
• T CAs are more likely to impair diabetic control as they increase serum glucose levels by up to 150%,
increase appetite  (particularly carbohydrate craving) and reduce the metabolic rate. They are generally
considered safe unless the diabetes is very poorly controlled or is associated with significant cardiac or
renal disease.
• Antidepressants such as amitriptyline, imipramine, duloxetine and citalopram are also used to treat painful diabetic
neuropathy.
Asthma • Antidepressant medications except MAOI may be used for patients with asthma without fear of interaction. Other
antidepressant like SSRIs, TCAs, etc., may be used for patient with asthma without any apprehension about drug
interaction.
Glaucoma • Antidepressants that cause or exacerbate acute close angle glaucoma include medications with anticholinergics,
serotonergic or adrenergic properties.
• TCAs have the greatest anticholinergic properties,
• SSRIs and SNRIs by virtue of their action on serotonin receptor can also cause mydriasis and thereby can produce
papillary block.
• Antidepressants lacking anticholinergic and serotonergic activity (bupropion) may be preferred.
• Benzodiazepines (Diazepam) have mild anticholinergics properties.
Obstructive uropathy • Prostatism and other forms of bladder outlet obstruction are relative contraindications to the use of antidepressant
medication compounds with antimuscarinic effects.
• Benzodiazepines, trazodone, and MAOIs may also retard bladder emptying.
• The antidepressant medications with the least propensity to do this are SSRIs, bupropion, and desipramine.
Parkinson’s disease • Bupropion, exerts a beneficial effect on the symptoms of Parkinson’s disease in some patients but may also induce
psychotic symptoms, perhaps because of its agonistic action in the dopaminergic system.
• MAOIs (other than selegiline, also known as L‑deprenyl, a selective type B MAOI is recommended in the treatment
of Parkinson’s disease) may adversely interact with L‑dopa products.
• Selegiline loses its specificity for MAO‑B in doses greater than 10 mg/day and may induce serotonin syndrome
when given in higher doses in conjunction with serotonin‑enhancing antidepressant medications.
• There is no evidence favoring any particular antidepressant medication from the standpoint of therapeutic efficacy
in patients with Parkinson’s disease complicated by depressive disorder.
• The theoretical benefits of the antimuscarinic effects of some of the TCAs in the treatment of patients with depressive
disorder with Parkinson’s disease are offset by the memory impairment that may result.
• ECT exerts a transient beneficial effect on the symptoms of idiopathic Parkinson’s disease in many patients.
• Amoxapine, an antidepressant medication with dopamine‑receptor blocking properties, may be avoided for patients
who have Parkinson’s disease.
• Lithium may in some instances induce or exacerbate parkinsonian symptoms.
Malignancy • In treatment of depression in subjects with malignancy, SSRI are considered to be the first line drugs. The advantage
of SSRI is that they can act as effective adjunct analgesic drugs, especially in neuropathic pain. Disadvantages
of SSRI are drug‑drug interaction with drugs that are metabolized by CYP450/3A4  (e.g.  cyclophosphamide,
doxorubicin). Fluoxetine, may be used with caution especially is patients with hepatic insufficiency, since it has
a long half‑life.
• TCAs are also good adjunct analgesics. But the disadvantages with TCAs are anticholinergic side effects and
orthostatic hypotension. They can also worsen their side effects of drugs like opioids (e.g. constipation and dry
mouth) which are often needed for pain control.
• Psychostimulants, with their rapid onset of action have some advantages for depressed cancer patients in the sense
of promoting a sense of well‑being, decreasing fatigue, stimulating appetite, potentiating the analgesic effect of
opioids and decreasing opioid induced sedation.
• The goal of psychological treatment in depressed patients with cancer is to reduce emotional distress, improve
morale, coping ability, self‑esteem and sense of control.
Drug induced depression • If medication induced depression is suspected, the suspected drug should be discontinued if possible and replaced
with another agent less likely to induce depression.
• When this is not possible or when discontinuation does not result in remission of the depressive symptoms,
pharmacotherapy for the depression may be considered.

Contd...

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Table 11: Contd...
Special situation Strategies
Liver disease • Liver impairment affects basic elements of medication pharmacokinetics, from absorption to metabolism,
distribution to elimination, changing drug levels, duration of action, and efficacy.
• Most antidepressants are highly protein‑bound‑ except, venlafaxine, and methylphenidate.
• In liver failure, a reduction in albumin and alpha1‑acid‑glycoprotein production, along with altered protein‑binding,
leads to higher levels of free pharmacologically‑active drug. This is offset by a compensatory increase in the rate of
hepatic metabolism, and this is especially important for drugs with low intrinsic clearance.
• Most antidepressants are highly lipid‑soluble and require hepatic metabolism (biotransformation into more polar
compounds) to allow them to be cleared from the body in urine or bile.
• Antidepressants can also be divided into two major categories of clearance, determined by their enzyme affinity.
Flow‑limited drugs have high hepatic extraction, and their hepatic clearance is dependent on the rate of delivery of
the drug to the liver. TCAs undergo significant first pass metabolism of greater than 50% after oral administration.
• Drugs with low hepatic‑enzyme affinity (e.g., paroxetine) are metabolized more slowly, as enzyme saturation is the
rate limiting step. The severity of impairment rather than the underlying aetiology is the most important factor to
consider in prescribing for this group. Renal function may also be affected.
• As the risk of drug toxicity increases with disease severity, lower starting and total doses of medication are
recommended (starting dose ‑about one forth that of adults).
Renal disease • In this group of patients, TCAs are probably safer than SSRIs.
• The degree of renal impairment rather than the cause is most important.
• Renal impairment may be present without a raised creatinine level. TCAs metabolites are excreted by the kidneys,
hence accumulation may occur. Of the SSRIs, sertraline is not recommended by its manufacturers in renal failure.
• Fluoxetine, citalopram and paroxetine may be started at very low dose in patients with a glomerular filtration rate
of at least>10 ml/min.
• Lithium may only be prescribed if absolutely necessary, at low doses, on alternate days, with frequent checking of
serum levels.
Perioperative period • TCAs may preferably be stopped prior to surgery. SSRIs and MAOI can interact with pethidine, pentazocine, and
dextromethorphan, at the pharmacodynamics levels and lead to serotonin syndrome, therefore such drugs may be
avoided during the perioperative period. However, SSRIs may not be discontinued in order to prevent anesthetic
interactions, except when the SSRI is used in combination with aspirin or an Non-steroidal anti-inflammatory
drugs and when the SSRI is used in patients over 80 years of age. In these patients, the balance of risks of
withdrawal and bleeding is to be discussed with patients. Because abrupt discontinuation can cause serious
withdrawal symptoms, the drugs may be gradually discontinued over few days to 2 weeks before surgery.
• Lithium can contribute to hemodynamic instabilities, interfere with sodium and potassium metabolism, and the
renal excretion of lithium can be reduced in presence of renal complications. The physical risk of intoxication,
with its detrimental and fatal risks for the central nervous system, is unacceptable. Therefore, lithium
discontinuation is recommended. Lithium can be stopped at once because no withdrawal symptoms occur.
• When, postoperatively, the patient is hemodynamically stable, is able and allowed to drink, and is not on new,
potentially interfering drugs, the medication may be restarted gradually.

antidepressant medication discontinuation syndromes.
Discontinuation syndromes have been found to be more
frequent after discontinuation of medications with shorter
half-lives, and patients maintained on short-acting agents
may be given even longer, more gradual tapering. Paroxetine,
venlafaxine, TCAs, and MAOIs tend to have higher rates of
discontinuation symptoms while bupropion-SR, citalopram,
fluoxetine, mirtazapine, and sertraline have lower rates. The
symptoms of antidepressants discontinuation include
flu-like symptoms, insomnia, nausea, imbalance, sensory
disturbances (e.g., electrical sensations) and hyperarousal
(agitation). If the discontinuation syndrome is mild,
reassurance may be sufficient. If mild to moderate, short-
term symptomatic treatment (analgesics, antiemetics, or
anxiolytics) may be beneficial. If it is severe, antidepressant
are to be reinstated and tapered off more slowly.
After the discontinuation of active treatment, patients
should be reminded of the potential for a depressive
relapse. Patient may be again informed about the early
signs of depression, and a plan for seeking treatment in
the event of recurrence of symptoms may be formulated.
Patients may be monitored for next few months to identify
relapse. If a patient suffers a relapse upon discontinuation
of medication, treatments need to be promptly reinitiated.
In general, the previous treatment regimen to which the
patient responded in the acute and continuation phase are
to be considered.
MANAGEMENT OF TREATMENT RESISTANCE
DEPRESSION
Initial treatment with antidepressant medication fails to
achieve a satisfactory response in approximately 20%-30%
of patients with depressive disorder. In some cases the
apparent lack of treatment response is actually a result
of faulty diagnosis, inadequate treatment, or failure to
appreciate and remedy coexisting general medical and
psychiatric disorders or other complicating psychosocial
factors. Adequate treatment for at least 4-6 weeks is

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Gautam, et al.: CPGs for depression

necessary before concluding that a patient is not responsive who has not responded to medication is carrying out
to a particular medication. First step in care of a patient a thorough review and reappraisal of the psychosocial
and biological information base, aimed at revarifying the
Depression diagnosis and identifying any neglected and possibly
No Response to treatment
contributing factors, including the general medical
problems, alcohol or substance abuse or dependence,
other psychiatric disorders, and general psychosocial issues
impeding recovery. Algorithm for arriving at the diagnosis
Reassess diagnosis Correct the diagnosis and of treatment resistant depression is given in figure-6.
treat accordingly

Some clinicians require two successive trials of medications

Has the patient received
adequate doses for
sufficient duration?
Is adherence to medication
proper?
Are Side effects interfering
with treatment?
Look for emerging organic
causes, rule out any other
comorbidities/stressors
Figure 6: Algorithm for arriving at the diagnosis of Treatment
Resistant Depression
of different categories for adequate duration before
considering treatment resistant depression (TRD).
Management of TRD involves addition of an adjunctive
agent, combining two antidepressants, addition of ECT
or other somatic treatments like rTMS.Algorithm for
management of TRD is given in figure-7.
Addition of an adjunct to an antidepressant: Lithium
is the drug primarily used as an adjunct; other agents
in use are thyroid hormone and stimulants. Opinion
differs as to the relative benefits of lithium and thyroid
Treatment Resistant supplementation. It is reported that lithium is useful in over
Depression
50% of antidepressant nonresponders and is usually well
tolerated. The interval before full response to adjunctive
lithium is said to be in the range of several daysto 3 weeks.

Treatment Resistant
Depression

Partial or no response

Augmentation with Combination Other e.g. Lamotrigine,

ECT/
Lithium/Thyroid / Antidepressants fluvoxamine,
rTMS
Buspirone (TCA + SSRI) or Mirtazapine+ Bupropion,
(Bupropion + SSRI) Olanzapine etc. (Provide
Rationale)

Continuation Phase

Maintenance Phase

Figure 7: Algorithm for management of Treatment Resistant Depression

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Gautam, et al.: CPGs for depression
If effective and well tolerated, lithium may be continued
for the duration of treatment of the acute episode. Thyroid
hormone supplementation, even in euthyroid patients,
may also increase the effectiveness of antidepressant
treatment. The dose proposed for this purpose is 25 μg/
day of triidothyronine increased to 50 μg/day in a week.
Simultaneous use of multiple antidepressants: Depression is
a chronic disabling condition in case patient does not respond
to single drug regimen; clinicians may use combination/
polytherapy with close monitoring of side effects and drug
interaction profile. Combinations of antidepressant carry
a risk of adverse interaction and sometimes require dose
adjustments. Use of a SSRI in combination with TCA has
been reported to induce a particularly rapid antidepressant
response. However, fluoxetine added to TCAs causes an
increased blood level and delayed elimination of the TCA,
predisposing the patient to TCA drug toxicity unless the dose
of the TCA is reduced. Another strategy involves combined
use of a tricyclic antidepressant and a MAO inhibitor, a
combination that is sometimes effective in alleviating severe
medication-resistant depression, but the risk of serotonin
syndrome necessitates careful monitoring.
Electroconvulsive therapy: Response to ECT is generally
good and the response rates are like any form of
antidepressant treatment and it may be considered in
virtually all cases of moderate or severe major depression
who do not respond to pharmacologic intervention.
Approximately 50% of medication resistant patients exhibit
a satisfactory response to ECT. Lithium may be discontinued
before initiation of ECT, as it has been reported to prolong
postictal delirium and delay recovery from neuromuscular
blockade.
Repetitive Transcranial Magnetic Stimulation (rTMS)
Repetitive transcranial magnetic stimulation (rTMS; a type of
TMS that occurs in a rhythmic and repetitive form) has been
put forward as a new technique to treat this debilitating
illness. Current evidence suggests that rTMS applied to the
left dorsolateral prefrontal cortex (DLPFC) is a promising
treatment strategy for depression, but not all patients show
a positive outcome. Current clinical outcome studies report
rather modest superiority compared with placebo (sham).
To date, it remains unclear which TMS parameters, such as
S50
stimulation duration and intensity, can produce the most
benefits. Moreover, there is no consensus of the exact brain
localization for individual coil placement.
MANAGEMENT OF SPECIAL CONDITIONS
Clinicians often encounter certain clinical situations which either
require special attention or can influence treatment decisions.
Management of these situations is summarized in table-11.
REFERENCES
1. American Psychiatry Association. Practice Guideline for the Treatment of
Patients With Major Depressive Disorder, Third Edition, 2010; pp -152.
2. Avasthi A, Grover S, Agarwal M. Research on antidepressants in India.
Indian J Psychiatry, 2010; 52 (Suppl): S341-354.
3. Avasthi A, Grover S, Bharadwaj R. Clinical Practice guidelines for
treatment of depression in old age. (Eds): Shiv Gautam & Ajit Avasthi.
Published by Indian Psychiatric Society, 2007; Volume III, 51-150.
4. Ellis P; Royal Australian and New Zealand College of Psychiatrists Clinical
Practice Guidelines Team for Depression. Australian and New Zealand
clinical practice guidelines for the treatment of depression. Aust N Z J
Psychiatry. 2004 Jun;38(6):389-407.
5. Gautam S, Batra L. Clinical Practice guidelines for management of
depression. (Eds): Shiv Gautam & Ajit Avasthi. Published by Indian
Psychiatric Society, 2005; Volume I, 83-119.
6. Grover S, Dutt A, Avasthi A. Research on Depression in India. Indian J
Psychiatry, 2010; 52 (Suppl): S178-S188.
7. Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P,
Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh
D, Milev RV, Müller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R;
CANMAT Depression Work Group. Canadian Network for Mood and Anxiety
Treatments (CANMAT) 2016 Clinical Guidelines for the Management
of Adults with Major Depressive Disorder: Section 3. Pharmacological
Treatments. Can J Psychiatry. 2016 Aug 2. pii: 0706743716659417. [Epub
ahead of print] PubMed PMID: 27486148.
8. Kessler RC, Bromet EJ. The epidemiology of depression across cultures.
Annu Rev Public Health. 2013;34:119-38.
9. Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R,
Parikh SV, Patten SB, Ravindran AV; Canadian Network for Mood and
Anxiety Treatments (CANMAT). Canadian Network for Mood and Anxiety
Treatments (CANMAT) clinical guidelines for the management of major
depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009
Oct;117 Suppl 1:S26-43.
10. National Institute of Health and Care Excellence. Depression in adults:
Recognition and Management. Clinical guideline (cg 90), 2009, pp 5-64.
11. Parikh SV, Segal ZV, Grigoriadis S, Ravindran AV, Kennedy SH, Lam RW,
Patten SB; Canadian Network for Mood and Anxiety Treatments (CANMAT).
Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical
guidelines for the management of major depressive disorder in adults. II.
Psychotherapy alone or in combination with antidepressant medication. J
Affect Disord. 2009 Oct;117 Suppl 1:S15-25.
12. Royal Australian And New Zealand College Of Psychiatrists Clinical
Practice Guidelines Team For Depression. Australian and New Zealand
clinical practice guidelines for the treatment of depression. Australian and
New Zealand Journal of Psychiatry Vol. 38, Issue 6, 2004.
13. Sarkar S, Grover S. A systematic review and meta-analysis of trials of
antidepressants in India for treatment of depression. Indian J Psychiatry
2014; 56: 29-38.
14. Singh T, Rajput M. Misdiagnosis of Bipolar Disorder. Psychiatry
(Edgmont).2006; 3: 57–63.
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CLINICAL PRACTICE GUIDELINES

Clinical Practice Guidelines for the Management of Generalised Anxiety

Disorder (GAD) and Panic Disorder (PD)
Shiv Gautam, Akhilesh Jain, Manaswi Gautam, Vihang N. Vahia, Anita Gautam

Participants of expert group on CPG for Generalised
Anxiety Disorder (GAD) and Panic Disorder
S.C Tiwari, Nilesh Shah, I.D. Gupta, B.N. Gangadhar,
Devendra Vijay Vergiya, Pratap Sharan
INTRODUCTION
Short description of anxiety disorders
Generalized Anxiety Disorder (GAD)
Definition: One of the anxiety disorders, where the primary
symptoms of anxiety are present at most days for at least
several weeks at a time, and usually for several months. The
symptoms should usually involve elements of:
(a) Apprehension (worries about future misfortunes,
feeling “ on edge”, etc)
(b) Motor tension (restlessness, inability to relax, trembling)
(c) Autonomic over activity (light-headedness, sweating,
tachycardia, tachypnea, dry mouth etc)
The transient appearance of depressive symptoms, does
not rule out the diagnosis of GAD as main diagnosis. The
sufferer must not meet the full criteria for depressive
episode, phobic disorder, panic disorder or OCD.
Patients with generalised anxiety disorder have high anxiety
and are worried about intrapsychic conflicts or external
environmental events. They have multiple somatic symptoms
of anxiety, restlessness, difficulty in concentration, irritability,
fatigue, muscular tensions and difficulty in sleeping
particularly early insomnia. They have vague apprehension
about future events and fear of unknown. Common features
observed in anxiety disorders include:
Address for correspondence:
Dr. Shiv Gautam, Director Professor, Gautam Institute of
Behavioral Sciences and Alternative Medicine, Jaipur.
E-mail: dr_shivgautam@yahoo.com
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Website:
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Panic Disorder- Episodes of intense fear or discomfort
accompanied by severe autonomic activity, palpitations,
sweating, dyspnoea, chocking sensation or other somatic
symptoms like chest pain, trembling, nausea, discomfort
or fluttering sensation in abdomen and impending fear of
death. Patient perceives it as a serious medical condition
and invariably reaches to a medical emergency setup where
after thorough physical evaluation he is declared normal.
Phobias-  Many patients with GAD suffer from irrational,
unrealistic fears and acute autonomic reactions to certain
specific situations or extreme fear to certan inanimate objects.
They include agarophobia (fear of open spaces) fear of crowds,
being out side home alone or traveling in a bus train or car.
Some may have fear in closed spaces (claustrophobia) fear of
heights (acrophobia) fear of opposite sex (hetero-phobia) fear
of sight of blood (erythrophobia) or fear of facing certain social
situations (social anxiety disorder) the common feature among
all phobias being intense fear, increased autonomic activity and
avoidance behavior (avoiding the fearful object or situation).
Obsessive compulsive disorder- (OCD) has been seperately
dealt with in details in these guidelines however the
patients suffering from OCD have recurrent repetitive
unwanted intrinsic thoughts (obsessions) or actions
(compulsions) or both which lead to extreme distress, loss
of time and impairment of functioning of the individual. The
obsessious include douts, ideas of contamination, sexual
thoughts or religious preoccupations or negative thoughts
towards gods/goddess, the compulsions include activities
like counting, checking, repeating, washing hoarding
and touching objects, some have to and fro movements
of body parts. Patient is aware of the irrationality of
thoughts/actions but cannot control them, which produces
intense anxiety and autonomic arousal with feelings of
helplessness and guilt.
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DOI:
Vahia VN, Gautam A. Clinical Practice Guidelines for the
Management of Generalised Anxiety Disorder (GAD) and
10.4103/0019-5545.196975
Panic Disorder (PD). Indian J Psychiatry 2017;59:67-73.

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Gautam, et al.: CPG for GAD & Panic Disorder

Post-traumatic stress disorder (PTSD) - Usually it occurs after COMMON INGREDIENTS OF MANAGEMENT

a terrifying event that involving physical or psychological PLAN (FLOW CHART-1 AND 2)
traumatic event. It may also occure because of witnessing
or experiencing a serious harm to other significant persons The aim of management is to provide relief in psychological
in life. Patients have terrifying recollections of the event, or and somatic symptoms and minimize the impairment. This
nightmares. Some patients have an experience of living the can be addressed in following ways.
event in an illusionary or imaginary situation with hallucinations,
or flashback episodes. The patients suffer from intense 1. Pharmacotherapy
psychological or physical distress. Many patients develop loss The drug treatment of GAD is some times required as long
of interest, estrangement from others, sleep disturbances, as 6-12 month treatment, some evidence indicate that
irritability, diffi culty concentrating, hypervigilance, and treatment should be long term.
exaggerated startle response. This phenomenon may persist
for one month or more before it is diagnosed. 2. Psychotherapy
i. Cognitive behaviour therapy
Natural history and course ii. Behavioural techniques
The age of onset is difficult to specify, as most of the patients iii. Supportive Psychotherapy
have been anxious for long but report late. Nearly 1/3rd of iv. Insight oriented Psychotherapy
the patients who have GAD seek psychiatric treatment.
Many go to GPs, physicians, cardiologist, chest specialist Goals
for the somatic component of the disorder. Because of the • Psycho-education Direct explanation of the symptoms
high incidence of co-morbid mental disorders, the course and disorder to the patient and the family.
and prognosis is difficult to predict.The occurrence of • Monitoring of anxiety
several negative life events greatly increases the likelihood • Cognitive restructuring: Corrects the hypothesized
that the disorder will develop. In all, a chronic condition cognitive distortions and helps to identify and counter
may be life long. fear of bodily sensations.

Patient Presenting with Anxiety

GAD
Diagnosis by ICD 10 Criteria

Psychopharmacology Psychosocial Intervention Psychopharmacology

combined with Psychotherapy

Benzodiazepines

Clonazepam Cognitive – behaviour therapy Long-term outcome is better when

Chlordiazepoxida
Diazepam
Alprazolam
Iniate from minimum adequate
Dose/ prescribed for a limited
Period (6-8 weeks)
Use with caution for dependence
Relaxation therapy they are used in combination.
Yoga & Meditation
Supportive Psychotherapy
Insight therapy
Family therapy
Psycho education

SSRIs Paroxetine; Sertraline; Fluoxetine Appendix– Flowchart - 1

Venlafaxine GAD
SNRI
Mirtazapine
NaSSA
Other Buspirone

TCA Tricyclic & Tetra cyclic

Beta Blockers Propranolol

Flowchart 1: Management of Generalized Anxiety Disorder

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Gautam, et al.: CPG for GAD & Panic Disorder

PANIC DISORDER
Diagnosed by ICD 10

Acute Attack Long Term Care

Psychopharmacological Psychotherapy Psychopharmacological Psychotherapy

Treatment Treatment

i. SSRI- i. CBT i. BZDs CBT

Fluoxetine ii. Psychodynamic ii. SSRIs Psychodynamic
Paroxitine Psychotherapy iii. TCAs Psychotherapy
Sertraline iii. Group therapy iv. Venlafaxine Group therapy
Fluvoxamine v. NaSSA
Citalopram vi. Beta Blockers
ii. BZDS (Propanlol)
Alprazolam Ravi Kiran Mathur
Clonazepam
Diazepam

iii. SNRI
Venlafaxine

iv. NaSSA

v. Beta Blockers : Propanlol

Useful when combined
With BZDs

vi. TCAs
Imipramine
Clomipramine

Flowchart 2: Management of Panic Disorder

Efficacy It includes history of present illness, current symptoms;

Cognitive Behavioural Therapy has proven efficy other
psychotherapies do help in ameliorating symptoms of
anxiety. It addresses cognitive distortions and somatic
symptoms. More effective with chronically anxious
patients, may need 8-10 sessions. It has been shown that
yogic techniques produced greater motivation to practice
than progressive relaxation Meditation was found to be as
effective as pharmacotherapy in controlling symptoms of
anxiety. The overall efficacy claims are backed by very few
Indian studies, but are useful. It requires considerable time
and discipline from the patients.
Adverse effects
These are relatively benign. Some patients may develop
dependence on the therapist and that needs cautious
vigil.
3. Combined pharmacological and psychotherapeutic
intervention
Long-term outcome is better when they are used in
combination.
ASSESSMENT AND EVALUATION
1. Performing a diagnostic evaluation
Psychiatric evaluation and physical examination
necessary.
past psychiatric history, general medical history and history
of substance use, personal history (eg. psychological
development, life events and response to those events),
social, occupational and family history; review of the
patient’s medications; physical and mental status
examination and adequate diagnostic tool and criteria.
Diagnose GAD according to ICD-10 (W.H.0,1992).
Anxiety should not be due to the other Axis I disorder
(eg. mood disorder, psychotic disorder, social phobia, OCD,
somatization disorder, hypochondriasis, PTSD) or a general
medical condition (eg. hyperthyroidism) or substance use
disorder (intoxication or withdrawal), (see appendix-1 for
flow chart).
2. Evaluating particular symptoms
Patients experience excessive anxiety but many of them
experience panic attacks, which may worsen the clinical
picture. The prolonged illness may cause depressive symptoms
with emergence of suicidality and substance abuse.
3. Evaluating severity of functional impairment
Many may continue to function in their social and
occupational lives with some impairment, others may
become severely incapacitated and give up their jobs and
is social duties. The impairment in different areas can be
assessed self-administered visual analog scale.

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Gautam, et al.: CPG for GAD & Panic Disorder
FORMULATING TREATMENTS AND CHOICE OF
TREATMENT SETTINGS
The aim of management is to provide relief in psychological
and somatic symptoms and minimize the impairment. This
can be addressed in following way.
1. Establishing and maintaining atherapeutic alliance
The treatment of GAD may be long lasting hence the
alliance is crucial. Understanding the life events, the extent
and severity of symptoms requires confiding and lasting
therapeutic relationship.
Attention to the patient’s worries and fears are essential for
long term gains
2. Monitoringthe patient’s psychiatric status
The symptomatic improvement in psychological and
autonomic symptoms leads to greater confidence in the
treating doctor. The anxiety goes slowly with treatment
and bursts of severe symptoms during the treatment need
constant monitoring.
3. Pharmacotherapy
The drug treatment of GAD is some times is seen as
a 6-12 month treatment, some evidence indicate that
treatment should be long term.
a). Goals
Reduce psychological and autonomic symptoms and other
co morbid conditions. Improve occupational and social
functioning.
b). Efficacy
Little Indian data to address the issue; mainly western data
available.
c). Adverse effects
Different for different class of drugs.
Selective serotonin reuptake inhibitors (SSRIs), serotonin-
norepinephrine reuptake inhibitors (SNRIs), and pregabalin
are recommended as first line drugs due to their favorable
risk-benefit ratio, with some differentiation regarding
the various anxiety disorders. The common category of
pharmacological agents used in management of generialised
anxiety disorders include SSRIs,SNRIs, Pregabalin, TCAs,
Benzodiazepines, Antihistamines, Atypical antipsychotics,
and Antioxidants. Role of vitamin A, C and E has been
evaluated and recommended in adequate doses for patients
suffering from GAD.
Dosing
Majority of patients respond to the low dose of
antidepressants (with the exception of OCD). In the elderly,
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treatment should be started with half the recommended
dose or less in order to minimize initial adverse drug events.
The antidepressant dose should be increased to the highest
recommended therapeutic level if the initial treatment with
a low or medium dose fails.
For patients who do not improve with standard treatments,
a number of alternative options should be tried including
augmentation with small dose of antipsychotics or adding
another anxiolytic agent or addition of non-pharmacological
therapy like cognitive behavioral therapy (CBT) or Yoga,
Meditation and increased physical activity as described
below.
4. Non-pharmacological treatment
Non pharmacological treatment found useful in treatment
of anxiety disorders include supportive therapy, Exposure
therapy (e.g. gradual exposure in vivo, “flooding”) and response
prevention. Psychoeducational advice, and suggesions to not
to avoid feared situations are helpful in management.
Cognitive Behavioural Therapy: Adequate strength of
evidence is available for Individual CBT, Group CBT and Self-
directed CBT. Choosing between medications and CBT is
determined by a number of factors, particularly the patient’s
preference, treatment options at hand, adverse drug
effects, onset of efficacy, comorbidity (e.g. with depression),
financial considerations, time availability, accessibility of
psychiatric and psychological treatment resources, and
experience of the clinician.
Steps of CBT shall include:
1. Psychoeducation
2. Self-monitoring
3. Systemic exposure to panic inducing cues
4. Countering anxious beliefs
5. Exposure to fear cues
6. Modify [mal-adaptive behaviors
7. Relapse prevention
8. Dealing with transference issues
9. Resolving interpersonal and other emotional issues.
Initial expectations and anticipation favoring CBT
• Accept that the worrying is out of control
• Perhaps, worrying offers some protective value.
• CBT will facilitate future adversities, despite the worrying.
During the course of the treatment, revised
understanding:
• The reasons for worrying and fears cannot be controlled
• Subjectively learn to control response to the fears and
worries
• Learn to obviate the behaviour of worrying
• Worrying does not have a protective value
• Actually, worrying reinforces negative thinking
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Gautam, et al.: CPG for GAD & Panic Disorder
Excesive worrying increases likely hood or more
anxieties in the future
CBT does not alter the method of managing source of
the worries
CBT helps to be better equipped to handle the future
stress.
Indian modules of psychotherapy
Several therapists have talked about Search of Indian
module of psychotherapy and it is a felt need to have such a
module, which is socially and culturally relevant.
Ancient Indian thought has provided very rich knowledge
regarding mind and its functioning. From the Vedic period
issues relating to mind, consciousness, understanding of
human life, its existence and the concept of Atman have
been widely studied and several explanations to improve
the quality of human life are available in Vedic and Post
Vedic literature. The Bhagvad Gita contains in condensed
form all the philosophical and psycholoical wisdom of the
Upanishads. Bhagwad Gita describes all aspects of yoga,
psychology and is unique among the psychlogical and
philosophical teachings for a student of psychotherapy,
various aspects of psychotherapeutic techniques are
described in it.
In this excellent module of Psychotherapy through
18 chapters way of self knowledge, the Yoga of action
(karma) knowledge of renunciation and action, the path of
meditation, knowledge of the absolute and eternal, yogic
vision, yoga of devotion, profound knowledge of three
Gunas and the wisdom of renunciation and liberation
have been described at length, which leads to personality
transformation of Arjuna. In the modern psychotherapy,
cognitive restructuring is the goal of psychotherapy, which
has been accomplished a great deal through Bhagwad Gita.
Prekshadhayan
A Jain Meditational technique propounded by Acharya
Mahapragya, which includes relaxation, meditation,
yoga, asanas and pranayam, a comprehensive capsule of
behavioural management has been tried in management of
GAD. On mental level, it proves to be an applied method
to train the mind to concentrate. It offers a way to treat
serious anxiety disorders with or without drugs. Large trials
of this technique are still awaited. At present, few scientific
studies are available.
5. Providing Education To The Patient And Family
This seemingly unimportant aspect is most relevant to
Indian settings where awareness of psychiatric illness and its
realization and need for treatment with compliance is little.
Many feel dejected, angry, isolated and may have suicidal
ideas. Family and the patient need to be told that this is like
any other illness that needs treatment and success depends
on compliance.
Indian J Psychiatry 59 (Supplement 1), January 2017
6. Addressing early signs of relapse
The education that the illness is a chronic relapsing
illness is essential and emergence of anxiety with or
without treatment should be promptly treated. Sudden
discontinuation may lead to emergence of withdrawal
symptoms thus early recognition by the patient and the
family helps in prompt treatment.
MANAGEMENT AS PER THE DIFFERENT STAGES
OF THE ILLNESS
The treatment recommendations for the different anxiety
disorders are summarized in Table I. Some antianxiety drugs
are effective in all anxiety disorders, whereas some drugs
have only been studied in specific anxiety disorders and thus
should be reserved for use in these particular disorders.
Panic disorder and agoraphobia. In acute panic attacks, mouth
desolving short-acting benzodiazepines and reassurance
to the patient may be sufficient. SSRIs SNRIs are first-line
treatments for longterm management. Patients should be
treated for atleast six to eight months or longer to prevent
relapses.
A combination of CBT and anxiolytic medication has been
shown to have the best treatment outcomes.
In GAD and Social anxiety disorder (SAD): Choice of Drugs for
Management are SSRIs, SNRIs and pregabalin. Buspirone and
hydroxyzine are second line treatment. Benzodiazepines
should only be used for long-term treatment when other
drugs or CBT have not shown results.
Specific phobia: Specific phobia should be treated with
behaviour therapy including systematic desensatisation.
SSRIs or short acting benzodiazepines should be tried in
cases not responding to behaviour therapy.
OCD: Choice of treatments is the SSRIs and the TCA
clomipramine. Cognitive behaviour therapy (CBT) and
exposure and response prevention are other proven
techniques of management.
PTSD: Choice of treatments includes the SSRIs and
venlafaxine. Therapeutic conversation, psychoeducation
and regrief therapy are non-pharmacological treatment
techniques advocated.
TREATMENT UNDER SPECIAL CONDITIONS
(FLOW CHART-3)
Pregnancy.The use of SSRIs and TCAs in pregnancy does not
have increased risk for malformations. It is recommended to
avoid paroxetine alprazolam use among pregnant women
or women planning to become pregnant.
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Gautam, et al.: CPG for GAD & Panic Disorder
Anxiety Disorder
Child and Adolescent Geriatric
Population Population
Scant Literature in West Lower initial dose
and India Lower target dose
SSRIs Gradual escalation
BZDs
Flowchart 3: Management of Anxiety Disorders in Special Population
Breast-feeding. SSRIs and TCAs are excreted into breast milk,
they do not cause any harm to the new born because the
concentration in breast milk is very small however infants of
mothers on benzodiazepines, should be observed for signs
of sedation, lethargy, poor suckling, and weight loss, and if
high doses have to be used and long-term administration is
required, breast feeding should probably be discontinued.
Treating children and adolescents. Choice of treatment
should be SSRIs concerns about increased risk of suicidal
ideation and behavior have ben reported therefore careful
monitoring is advisable, presence of comorbid depression
should be looked fore.
Treating the elderly. Elderly have increased sensitivity for
anticholinergic properties, an increased risk for orthostatic
hypotension, and ECG changes during treatment with TCAs,
and possible paradoxical reactions to benzodiazepines,
which include depression, with or without suicidal
tendencies, phobias, aggressiveness, or violent behavior.
Thus, treatment with TCAs or benzodiazepines is less
favorable, while SSRIs appear to be safe.
Treatment of patients with severe Physical disease. Patients
with cardiovascular, cerebrovascular and endocrine disease,
irritable bowel syndrome, malignency, stroke, chronic
obstructive pulmonary disease (COPD) hyperthyroidism
may have associated anxiety reactions with their somatic
disease state. Such anxiety disorders may compound the
management and the prognosis of these primary conditions.
Advocated pharmacological agents in such conditions
include SSRIs and Venlafaxine.
WHEN TO STOP TREATMENT
Decesion to stop treatment will depend on clinical
response of the patients. Usualy the treatment is stopped
in a tapering manner after atleast 6 months stability of
clinical improvement and asymptomatic status of the
patient. Before stopping the treatment, the nature of illness
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Suicidal Patient Substance use
disorder
Adequate dose Treatment of substance
Inform patient’s family use disorder essential
possibilities of recurrence, response to triggers and his/
her ability to cope with the situation should be discussed
at length. Patient’s personal view should be included in
decesion making of stopping the treatment. Patient should
be encouraged to adapt alternative methods of anxiety
reduction like yoga, pranayam, relaxation techniques
including progressive muscular relaxation (PMR)/Shavasan
etc. which can be mastered by him before weaning off the
smallest dose of antianxiety medication. Mindfulness-Based
Cognitive Behavior Therapy (MBCBT) for reducing cognitive
and somatic anxiety and modifying dysfunctional cognitions
in patients with anxiety disorders has been tried where in
different versions of mindfulness meditation, cognitive
restructuring, and strategies to handle worry, such as,
worry postponement, worry exposure, and problem solving
have been employed. However, these studies are on small
number of patients and need carefull review for further
application.
MANAGEMENT OF SIDE EFFECTS OF
MEDICATION
Diffrent side effects will emerge with different category of
antianxiety medication. They should be carefully observed
and addressed to. Side effects of medication can be drug
related or dose related. If it is drug, related, alternative class
of drug should be tried for adequate length of time. If it is
dose related then the dose of the drug has to be reduced.
Things to remember for GAD:
1. Anticholinergic and cardiovascular side effects to be
kept in mind when using tricyclic and Tetra cyclic for
side effects. Precaution in suicidal patients.
2. Long-term treatment may be required.
3. Psychopharmacological therapy combined with
psychotherapy works better.
SUGGESTED READING
1. Guidelines for the pharmacological treatment of anxiety disorders,
obsessive – compulsive disorder and posttraumatic stress disorder in
Indian J Psychiatry 59 (Supplement 1), January 2017
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Gautam, et al.: CPG for GAD & Panic Disorder
primary care review article international Journal of Psychiatry in Clinical
Practice, 2012; 16: 77–84.
2. Generalised anxiety disorder in adults – diagnosis and management www.
bpac.org.nz keyword: anxiety.
3. Spirituality and mental health edited by Dr. Avdhesh Sharma, Published by
Indian J Psychiatry. 2008 Oct-Dec; 50(4): 233–237.
4. Indian Culture and Psychiatry, Shiv Gautam, Nikhil Jain, Published
by Indian Journal of Psychiatry year 2010 Volume 52 Issue 7
(P. 309-3013).
5. Prekshadhyan, Manaswi Gautam, published in spirituality and mental
health by Indian psychiatric society task force editor Avdesh Sharma
(2008-2009): 163-176.
6. Mental Health in Ancient india and its relevence to modern psychiatry.
Shiv Gautam Presidential Address, Indian Journal of Psychiatry (1999)
41 (1) 5-18 and “spirituality and mental health, task force (2008-2009):
25-52.
7. ORIGINAL ARTICLE: Role of antioxidants in generalised anxiety disorder
and depression Medhavi Gautam, Mukta Agrawal, Manaswi Gautam,
Praveen Sharma, Anita Sharma Gautam, Shiv Gautam Indian Journal of
Psychiatry, Year 2012, Volume 54, Issue 3 [p. 244-247].
8. Rickels, K., Schweizer.E. (1990) The clinical course and long term
Indian J Psychiatry 59 (Supplement 1), January 2017
management of generalized anxiety disorder. J. Clin. Psychopharmacology,
10, 101S.
9. Caulpepper.L. (2003) Evidence for using Atypical Antipsychotic in mood
and anxiety disorders. Primary Care Companion, Journal of Clinical
Psychiatry,5, Supl(3) page 27-32.
10. Chandrashekhar,C.R. and Reddy,M.V.(1998). Prevalence of mental and
behavioural disorders in India: A meta-analysis,UP, 40(2):149-157.
11. Levitt.J.T., Hoffman,E.C., Grisham, J.R., Barlow.D.H. (2001) Empirically
supported treatments for panic disorder. Psychiatr. Ann.,31,(8): 478.
12. Ontario guidelines for Management of Anxiety disorder.Primary
care(2000). 1st Edn. Pollock.M.H., Mathews.J., Scotter (1998) Gabapentin
as it for Anxiety disorder.American Journal of Psychiatry, 155,992.
13. Sahasi.G., Chawala.H.M., Dhar.N.K., Katiyar.M. (1991) Comparative
study of progressive relaxation and yogic techniques of relaxation in
management of anxiety Neurosis, UP 33 (1);27-32.
14. World Health Organization (1992) The ICD-10 Classification of Mental and
Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines.
World Health Organization, Geneva.
15. Vahia.V.N., Shetty.H.K., Motiwala, S., Thakkar.G., Fernandes.L,
Sharma, C.J. (1993) Effect of Meditation in Generalised Anxiety
Disorder,35 (2);87-92.
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CLINICAL PRACTICE GUIDELINES
Clinical practice guidelines for Obsessive-Compulsive Disorder
Y.C. Janardhan Reddy, A. Shyam Sundar, Janardhanan C. Narayanaswamy, Suresh Bada Math
Department of Psychiatry, OCD Clinic, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore,
Karnataka, India
Participants of expert group on CPG for Obsessive
Compulsive Disorder
Adarsh Tripathi, Om Prakash Singh, Paramjeet Singh,
Tushar Jagawat, M, Aleem Siddiqui, K.K. Verma,
D.M. Mathur
INTRODUCTION
Obsessive-compulsive disorder (OCD) is a common
psychiatric illness with lifetime prevalence of 1-3% [1]. It is the
fourth-most common psychiatric illness and a leading cause
of disability. OCD is associated with significant impairment
in functioning, quality of life and disability. If untreated, OCD
is a chronic illness with a waxing and waning of symptoms.
A recent meta-analysis of long-term naturalistic prospective
studies demonstrated that nearly a half of patients experience
remission with much higher rates of remission in Indian
patients compared to those in the west [2]. Early diagnosis
and appropriate treatment may improve outcomes. Despite
OCD being a common mental illness, most seek treatment
after several years of suffering. Those who suffer from
OCD tend to be secretive about their symptoms and suffer
from shame and embarrassment. Less than a third of OCD
sufferers receive appropriate pharmacotherapy and even less
receive evidence-based psychotherapy.
Symptoms
The hallmarks of OCD are presence of obsessions and
compulsions. Obsessions are repetitive, unwanted,
Address for correspondence:
Y. C. Janardhan Reddy,
Professor of Psychiatry, NIMHANS, Bangalore 560029,
Karnataka, India.
E-mail: ycjreddy@gmail.com
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DOI:
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S74
intrusive thoughts, images or urges that are mostly ego-
dystonic and cause severe distress or anxiety. Compulsions
(or rituals) are repetitive behaviours or mental acts that
are performed in response to an obsession to reduce
anxiety/distress or prevent a dreaded consequence.
Obsessions and compulsions are time consuming,
distressing and are often resisted unsuccessfully. Clinical
manifestations of OCD are remarkably similar across
cultures and geographic locations. Common obsessions and
compulsions and symptom dimensions identified through
factor-analytical studies are shown in Table 1.
Diagnosis
Many people experience intrusive thoughts and exhibit
repetitive behaviours. A diagnosis of OCD is made only if
symptoms are time consuming (e.g., more than an hour
per day), distressing or cause significant interference in
functioning. This is reflected in DSM-5 diagnosis of OCD
and in the upcoming ICD-11 [3]. The ICD-11 criteria for OCD
are likely to be very similar to the DSM-5 criteria [3, 4]. The
ICD-11 may include an insight specifier along the same lines
as DSM-5. There are sweeping changes to the description
of OCD in the proposed ICD-11. Duration criteria and
subtyping of OCD may be removed in the revision for lack
of evidence and clinical relevance. In ICD-10, a diagnosis of
OCD was discouraged in the presence of schizophrenia, tic
disorder or depression. This criterion too may be removed
paving the way to make a diagnosis of OCD even in the
presence of these comorbid disorders.
Another major change to the diagnosis of OCD is creation
of OCD and related disorders in DSM-5 (and in the ICD-
11) and exit from the group of anxiety disorders. Many
disorders are included in this group: body dysmorphic
This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
How to cite this article: Janardhan Reddy YC, Sundar AS,
Narayanaswamy JC, Math SB. Clinical practice guidelines
for Obsessive-Compulsive Disorder. Indian J Psychiatry
2017;59:74-90.
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Reddy, et al.: CPGs for OCD
Table 1: Common symptoms of OCD
Obsessions
Contamination related obsessions
• Concern/disgust with bodily secretions and waste such as stools and urine
• Fear of dirt or germs/infections, concern with sticky substances
• Fear of getting ill because of contaminants (e.g., AIDS)
Sexual obsessions
• Unwanted, forbidden sexual thoughts, images or urges about strangers,
family friends, etc
• Sexual thoughts of molesting children, thoughts of sexual identity (am
I a gay?)
Harm/aggression related obsessions
• Fear might harm self or others (fear of jumping off the building, fear
of harming babies, stabbing a friend, running over pedestrians while
driving etc)
• Violent/horrific images (murders, mutilated bodies, accidents)
• Fear of uttering obscenities
Religious/blasphemy
• Sacrilege and blasphemy (blasphemous thoughts, fear of uttering insults
to God)
• Excessive concern about right/wrong, morality
Pathological doubts about daily activities (doubts of having not locked
doors, turned off gas knobs)
Need for symmetry and exactness
• Concern about things being not properly aligned, symmetrical, perfect
or exact
• With magical thinking (child may have an accident if things are not
properly arranged in kitchen)
Miscellaneous
• Need to know/remember (number plates, advertisements etc.)
• Intrusive non‑violent images, thoughts
• Superstitious fears (passing a cat, cemetery)
• Lucky/unlucky numbers, colors
Compulsions
Washing/Cleaning (excessive or ritualized hand washing, showering,
bathing, brushing/excessive cleaning of household items, floors, kitchen
vessels etc) in response to contamination obsessions
Checking
• In response to pathological doubts (appliances, locks, stove, doors)
• To prevent harm to self or others (check to make sure that you have not
caused accident, examining for injuries etc.)
Repeating
• Re‑reading or rewriting because you didn’t understand or write properly
• Repeating routine activities (going in and out of doorway, sit and stand
up repeatedly, repeating till you feel just right)
Counting (money, floor tiles)
Ordering and arranging (often till you feel just right)
Miscellaneous
• Mental rituals (praying, replacing bad thought with good thought)
• Superstitious behaviours
• Need to tell/ask/confess
Symptom dimensions[41]
• Contamination fears and cleaning/washing
• Forbidden thoughts (aggression, sexual, religious, and somatic
obsessions and checking compulsions)
• Symmetry (symmetry obsessions and repeating, ordering, and counting
compulsions)
• Hoarding (hoarding obsessions and compulsions)
disorder (BDD), trichotillomania (TTM), skin picking
disorder, hoarding disorder, substance/medication-
Induced obsessive-compulsive and related disorder
and obsessive-compulsive and related disorder due to
another medical condition. In the upcoming ICD-11, few
Indian J Psychiatry 59 (Supplement 1), January 2017
other conditions find a place in this group that include
tic disorders, hypochondriasis and olfactory reference
syndrome. All these disorders are grouped together based
on shared clinical features (e.g., repetitive behaviours),
comorbidity patterns, familiality, neuropsychological
deficits, treatment response and importantly shared brain
circuitry abnormalities. Hoarding disorder which may not
share many features with OCD is grouped along with OCD
because of historical association with OCD and obsessive-
compulsive personality disorder.
Comorbidity
OCD is often comorbid with other psychiatric disorders. It
is important to assess all patients with OCD for associated
psychiatric comorbidity since they may have an effect on
treatment outcome if left untreated. Depression and anxiety
disorders are present in over a half of patients seeking
treatment for OCD. Common comorbid disorders are
listed in Table 2. Those with early onset OCD, in particular
those with onset in childhood have high rates of attention
deficit hyperactivity disorder (ADHD), oppositional defiant
disorder (ODD) and tic disorders.
Bipolar disorder, in particular type 2, is reported to
be not uncommon in OCD [5]. Similarly, OCD is not
uncommon in those with primary diagnosis of bipolar
disorder [6, 7]. OCD when comorbid with bipolar disorder
tends to run an episodic course [8] with worsening of
symptoms in depressive phases and improvement in
hypomania/ mania phases. It is important to recognise OCD-
bipolar comorbidity because of treatment implications. The
specific serotonin-reuptake inhibitors (SSRIs) traditionally
used to treat OCD may induce switch to mania or rapid
cycling course.
Obsessive-compulsive symptoms and OCD are not
uncommon in schizophrenia. Nearly a third of schizophrenia
patients report OC symptoms or OCD. Presence of OCD
may have a negative effect on the long-term course of
schizophrenia. Therefore treatment of OCD with SSRIs
and cognitive-behavior therapy (CBT)/behavior therapy (BT)
may have to be considered although there is not much of
systematic evidence supporting their efficacy in treatment
of OCD in schizophrenia.
COMMON INGREDIENTS OF MANAGEMENT
PLAN
Common ingredients of managing OCD include the
following:
1. Detailed assessment of symptoms and comorbid patterns
including suicidal behaviours either by unstructured
clinical interview alone or supplementation with
structured assessments.
2. Decision on setting for treatment (outpatient vs. inpatient
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Reddy, et al.: CPGs for OCD
Table 2: Comorbid disorders in OCD
Mood disorders
• Major depression
• Dysthymia
• Bipolar disorder
Anxiety disorders
• Panic disorder
• Generalized anxiety disorder
• Social Phobia
OCD related disorders
• Body dysmorphic disorder
• Hypochondriasis
• Trichotillomania
• Skin picking disorder
• Tic disorders
Attention deficit hyperactivity disorder
Oppositional defiant disorder
Personality disorders
• Obsessive‑compulsive personality disorder
• Anxious‑avoidant personality disorder
• Borderline personality disorder
• Schizotypal personality
Differential diagnoses to consider
• Depression (depressive ruminations are usually ego‑syntonic, reflective
of depressive cognitions such as self‑criticism, failure, regret, guilt,
pessimism without any compulsions)
• Generalized anxiety disorder (anxious ruminations are about real‑life
concerns and not associated with compulsions)
• Body dysmorphic disorder (concerns limited to physical appearance)
• Trichotillomania (limited to hair pulling)
• Skin picking disorder (confined to excessive skin picking)
• Hoarding disorder (difficulty in discarding or parting with possessions,
accumulation of possessions; not secondary to obsessions)
• Eating disorders (confined to weight and food)
• Tics (often preceded by premonitory sensations and not aimed at
neutralizing obsessions)
• Psychotic disorders (Even poor insight/delusional OCD is associated
with typical obsessional content and compulsions whereas delusions
have persecutory, grandiose themes with other symptoms such as
hallucinations or formal thought disorder)
• Obsessive‑compulsive personality disorder (enduring and pervasive
pattern of excessive preoccupation with perfectionism, orderliness
and rigid control; rigidity, stubbornness, scrupulosity and over
conscientiousness. Typically ego‑syntonic. No obsessions and
compulsions)
care depending upon the severity, treatment resistance
etc.)
3. Detailed psychoeducation of the patient and family
member (s) about OCD, its course and treatment
options including duration of treatment.
4. Choice of treatment: drugs vs. CBT vs. combination
5. In the Indian context, SSRIs are first-line treatments
preferred over CBT because of feasibility, affordability
and limited number of trained therapists. CBT may be
considered if SSRIs alone are not beneficial.
6. Discussion on side-effects of drugs; in women risks vs.
benefits of drugs during pregnancy and in the post-
partum period
7. Follow-up plan after initiating treatment
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ASSESSMENT AND EVALUATION
In routine clinical practice, use of structured /
semistructured interviews and rating scales may not be
necessary. They are optional. However, they may be used
when the clinician needs supplementary information. A list
of useful instruments in the assessment of OCD is provided
in Table 3.
The Yale-Brown Obsessive-Compulsive Scale (YBOCS) is the
most widely used severity rating scale for OCD in both adults [9]
and children [10] and is considered a gold standard instrument
to measure severity of OCD. It is a 10-item observer-rating scale,
also available as self-rated instrument. It measures the overall
severity of obsessive-compulsive symptoms for the preceding
week. The YBOCS is a global measure of symptoms and does
not provide severity of individual symptom dimensions. A
total score of ≥ 16 is considered to be indicative of clinically
significant OCD. The YBOCS severity scale also has an
associated symptom check list of 15 categories of obsessions
and compulsions including miscellaneous symptoms. The
checklist elicits both current (1 month) and past symptoms.
On the YBOCS item-11 insight scale, the insight is graded
as follows: 0 = excellent (fully rational thinking), 1= good
insight (readily acknowledges absurdity or excessiveness
but has some lingering doubts), 2 = fair insight (reluctantly
admits absurdity, but waivers; has some unrealistic fear but
no fixed conviction), 3 = poor insight (overvalued ideas;
maintains they are not unreasonable or excessive, but
acknowledges validity of contrary evidence), and 4 = lack
of insight (delusional). A higher score on the Y–BOCS item-
11 indicates poorer insight.
FORMULATING A TREATMENT PLAN
Formulating a treatment begins with correct diagnosis of OCD
as per the DSM or ICD classificatory systems. When feasible
a structured clinical interview is recommended to obtain a
comprehensive account of patient’s problems. Once a diagnosis
is established, a detailed assessment of symptom profile is
mandatory. Family members often accommodate patient’s rituals
and contribute to poor outcome. In most severely ill patients, an
elaborate family assessment may be needed. Once assessment is
complete, short-term and long-term goals of treatment have to be
established. Enhancing treatment adherence is a vital aspect of
formulating a treatment plan. It is important to educate patients
about lag in the onset of action of drugs and that improvement
may occur over several months of continuous treatment. Brief
education about basic principles of psychotherapy should
be explained if psychotherapy is being planned. Essentials of
formulating a treatment plan are summarized in Table 4. All
patients and their immediate family members should be provided
psychoeducation about OCD (Table 5).
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Table 3: Commonly used instruments to assess
OCD (optional)
Diagnostics interview schedules
• The Mini International Neuropsychiatric Interview (MINI)[42]
• Structured Clinical Interview for DSM‑5 (SCID‑5)[43]
Severity rating scales
• Yale‑Brown Obsessive‑Compulsive Scale (YBOCS): symptom checklist
and severity rating scale (adult and child versions)[9,10]
• Dimensional YBOCS (DYBOCS)[44]
Scales to assess insight in OCD
• Yale‑Brown Obsessive‑Compulsive Scale (YBOCS), Item 11[9]
• Brown‑Assessment of Beliefs Scale (BABS)[45]
• Overvalued Ideas scale (OVIS)[46]
Obsessive‑beliefs questionnaire (OBQ) to measure beliefs underlying
obsessions [47]
The Family Accommodation Scale (FAS) assesses the degree to which
family members of those with OCD accommodate patient’s compulsions/
rituals[48]
CHOICE OF TREATMENT SETTINGS
In the Indian scenario, treatment is either on an outpatient or an
inpatient basis. Outpatient treatment is usually sufficient for most
OCD patients who are mild to moderately ill and for those who
are likely to be adherent to treatment. Patients may be followed-
up at periodic intervals, initially once in a month or two and
subsequently at longer intervals depending upon the response to
treatment and tolerability and side-effects. Hospital treatment may
be considered for those who are at high suicide risk, dangerous
to self or others, and intolerant to side-effects. Many severely
ill and treatment-resistant patients may require prolonged (2-3
months) hospitalization for intensive treatment with CBT and for
rationalization of pharmacotherapy. Inpatient care may also be
required for severe depression, mania or psychosis that may be
comorbid with OCD. Admission in rehabilitation services may be
necessary for some patients who may not have benefited from
standard treatments including inpatient care.
PHARMACOLOGICAL TREATMENT
The clinical practice guideline is framed based on a
review of relevant scientific literature. As a first step, we
framed relevant questions which arise in the minds of the
practitioner while treating a patient suffering from OCD.
A literature search was conducted in PubMed to answer
these questions. We also reviewed the existing guidelines
on treatment of OCD [11-14]. After a thorough literature
review, the treatment strategies were rated based on the
Strength of Recommendation Taxonomy (SORT) [15].
Consistent evidence from multiple randomized controlled
trials (RCT) constitutes the highest level of evidence for a
recommendation. However, the external validity of RCTs has
been questioned due to the rigid protocols in undertaking the
studies. A practitioner may make a clinical decision based on
the available evidence considering other relevant factors that
influence the decision making process. A non-exhaustive list
of these factors might include psychiatric and other medical
Indian J Psychiatry 59 (Supplement 1), January 2017
Table 4: Essentials of formulating a treatment plan
Establishing a diagnosis if OCD
Diagnosis of comorbid disorders (optional structured clinical interview)
Detailed evaluation for a range of OCD symptoms (clinical interview/
YBOCS or similar check list)
Detailed symptom evaluation
• Identify principal symptoms that are the target of treatment (especially
useful to identify principal symptoms if CBT is planned)
• Identify proxy compulsions, avoidance and safety behaviours
• Determine level of insight
• Assess family accommodation of patient’s rituals
Short‑term goals
• To achieve clinical response and if possible remission
• Remission of depression, if comorbid
• Help deal with suicidal thoughts, behaviour if any
• To determine tolerability to medicines
• Identify and manage side‑effects
Long‑term goals
• Achieve recovery
• Restore psychosocial functioning and enhance quality of life
• Long‑term treatment to prevent relapses
Enhancing treatment adherence
• Psychoeducation to the patient and family members
• Provide education materials to patient and family members
• Deal with unrealistic expectations of quick recovery; educate
patients and family about lag in the onset of action of drugs and that
improvement may occur over several months
• Sensitise patient about potential side‑effects and help to deal with them
• Use medicines that are effective, easily available and affordable
• Treat comrbid disorders and personality disorders if any; if left
untreated may contribute to poor treatment adherence
Enhancing adherence to psychotherapy (CBT)
• Detailed education about principles behind exposure and response
prevention
• Reassure that exposure and response prevention will be graded and
tasks will be determined based on collaborative approach
• Emphasize the role of motivation, home‑work compliance and need to
tolerate some anxiety
• Reduce unrealistic expectations of quick recovery
comorbidities, previous treatment trials, affordability, accessibility,
hypersensitivity, side-effect profile, patients’ values etc.
RELEVANT CLINICAL ISSUES
1. First-line pharmacological treatment for OCD
Meta-analyses of RCTs show that selective-serotonin
reuptake inhibitors (SSRIs) are significantly more effective
than placebo in the treatment of OCD [16]. SSRIs are
associated with many adverse effects but are usually well
tolerated. The only other medication which has shown to be
consistently effective in OCD is the serotoninergic tricyclic
antidepressant clomipramine. Clomipramine has been found
to be significantly more effective than placebo in multiple
RCTs and meta-analysis of RCTs [16]. Network meta-analysis
comparing the efficacy of clomipramine vs. SSRIs failed to find
any efficacy advantage over SSRIs [16]. Most head-to-head
comparison trials have not found any significant difference
between the efficacy of clomipramine and SSRIs [17].
Further, meta-analyses and individual RCTs have found that
the tolerability of clomipramine is worse than that of SSRIs
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Table 5: Components of psychoeducation Table 6: Medications recommended as monotherapy in

• Obsessions and compulsions are symptoms of OCD and that they are OCD
similar in most people who suffer from OCD; OCD is a brain disorder Drug Suggested dosage Strength of recommendation*
• Obsessions are not a reflection of one’s character or unresolved mental
Escitalopram 20‑30 mg A
conflicts
Fluoxetine 60‑80 mg A
• Explain the link between the components-Obsessions, compulsions and
Fluvoxamine 200‑300 mg A
distress
Paroxetine 40‑60 mg A
• Clarify myths and misconceptions about the illness
Sertraline 150‑200 mg A
• Explain the biological and psychological basis of OCD : OCD is a
Citalopram 40‑60 mg A
problem of aberrant functioning of certain brain circuits involved in
Clomipramine 150‑225 mg A
disregarding unwanted thoughts, dysfunction of certain neurotransmitter
Venlafaxine 225‑300 mg B
systems such as serotonin and glutamate, faulty interpretation
and excessive importance given to certain intrusions resulting in *Based on modified Strength of Recommendation Taxonomy (SORT)[15]
A – Consistent, good‑quality patient‑oriented evidence i.e., Meta‑analysis of
manifestation of obsessions Randomized controlled trials (RCT) with consistent findings or high quality
• Discuss the course and outcome of OCD-regarding the waxing and individual RCT
waning course with optimism that outcome is good in a majority of the B – Inconsistent or limited‑quality patient‑oriented evidence i.e., systematic
people if adequately treated review/meta‑analysis of lower quality clinical trials or studies with inconsistent
• Provide information regarding the available treatment strategies : findings/lower quality clinical trial/cohort study/case‑control study
C – Consensus based clinical guidelines extrapolations from bench research,
pharmacotherapy and cognitive behavior therapy
disease‑oriented evidence, usual practice, opinion, case‑series
• Sensitize with the idea that treatment is a continued process and often
long‑term
• Educate that medications take time to work, sometimes as long as few Table 7: Predictors of response to SSRIs
months before appreciable improvement is seen
Clinical predictors of poor response
• Psychological treatment too needs sustained efforts and sometimes
Early age of onset
booster sessions
Longer duration of illness
• Prevention of relapse addressed within the general context of OCD as a
Poor insight
chronic disorder
Presence of hoarding, sexual/religious obsessions, cleaning/washing,
• Educate the family regarding the need to reduce expressed emotions
repeating/counting compulsions
such as criticality, accommodative behaviors and proxy compulsions;
Comorbidities in the form of tics and depressive disorder
thus being supportive in the treatment process
Comorbid schizotypal, borderline and anxious avoidant personality
disorders
Neuroimaging predictors
[13, 17]. The anticholinergic, cardiac and neurological side
Lower baseline orbitofrontal cortex (OFC) and anterior cingulate
effects of clomipramine may be problematic in this regard. cortex (ACC) metabolism and greater pretreatment caudate metabolism
predicted better response (PET studies)
CONSIDERING THE CONSISTENT EFFICACY Reduction in thalamic volume and increase in OFC volume is associated
AND BETTER TOLERABILITY, GUIDELINES with SSRI response (structural MRI)
Increased dorso-lateral prefrontal cortex (DLPFC) activation with
RECOMMEND SSRIs AS FIRST LINE
Stroop task and decreased activation of frontal regions with symptom
TREATMENT FOR OCD (TABLE 6). provocation task predicted good response
Genetic predictors
Choice of SSRI Specific polymorphisms in the promoter region of serotonin transporter (5
Meta-analyses comparing the different SSRIs [16] and direct HTTLPR) associated with treatment response
CYP2D6 polymorphisms associated with SSRI response
head-to-head comparisons [17,18] have not shown superiority
Ref:[49]
of any one SSRI over the other. SSRIs differ to some extent
in their propensity to cause certain adverse effects and drug
interactions. However, there is no unequivocal evidence to higher dose of SSRI than that used in depression (Table 5). A
suggest that these differences may be clinically meaningful. meta-analysis of fixed-dose comparison studies have found a
Recently, concerns have been raised regarding cardiac greater efficacy with higher doses of SSRI (60-80 mg fluoxetine
adverse effects with high dose of citalopram, which is equivalent) compared to medium (40-50 mg fluoxetine
commonly used in OCD. Hence, high-dose citalopram may be equivalent) and low doses (20-30 mg fluoxetine equivalent)
used with caution in those with risk for arrhythmias. [19]. However, all three dose ranges were significantly more
effective than placebo. The increased efficacy comes at the
THE PRACTITIONER IS RECOMMENDED TO cost of poor tolerability as evidenced by increased dropouts
CHOOSE AN SSRI FOR AN INDIVIDUAL PATIENT due to adverse effects [19]. A review of individual fixed-dose
BASED ON FACTORS SUCH AS PREVIOUS comparison studies found that the dose-response relationship
RESPONSE, COMORBIDITY, TOLERABILITY, is more evident for escitalopram, fluoxetine and paroxetine,
ACCEPTABILITY, ADVERSE EFFECTS, COST AND while it is less clear-cut for citalopram and sertraline [17].
DRUG INTERACTIONS. Clomipramine has not been tested in such fixed dose
comparison studies. However, most studies have employed a
Dose of SSRI flexible dosing at 150-250 mg [17]. It should be remembered
It is generally recommended that OCD be treated with a that there is likely to be inter-individual differences in

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Reddy, et al.: CPGs for OCD

SSRI© CBT/BT
First line +SSRI**
CBT/BT #
treatments*
response

Response after No
15-20 sessions SSRI: If recovered or minimal
symptoms continue for 1-2
Yes years & then gradual taper
over several months.
Inadequate Indefinite treatment:
Continue till remission response Persistent symptoms,
with periodic booster previous history of relapses,
sessions for severe illness
4-6 months CBT: booster sessions for
4-6 months

Partial response No response

Options
Options • 2nd SSRI / CBT( if not
• CBT/BT (if not offered) Inadequate offered)
• Aripiprazole/risperidone response • Clomipramine / CBT (if
• Memantine not offered)
• Lamotrigine • Other untried SSRIs
• 5HT-3 antagonists • Venlafaxine

Inadequate
response

Other experimental treatments

• Ultra-high dose SSRI
• Augmentation with
clomipramine
• Ketamine
• rTMS€ /tDCS$
• Riluzole/N-acetyl cysteine

Ablative neurosurgery/ Deep

brain stimulation

Figure 1: Treatment algorithm for treating a patient with OCD. *First line treatment chosen based on feasibility and severity
of illness, #CBT/BT- Cognitive behavior therapy/Behavior therapy, @SSRI – Selective serotonin reuptake inhibitor, %rTMS-
repetitive transcranial magnetic stimulation, $ - tDCS- transcranial direct current stimulation. ** Preferred for severe OCD

pharmacokinetic profile of drugs due to intrinsic variations in
drug metabolism and drug interactions.
GUIDELINES RECOMMEND TREATMENT OF
OCD WITH HIGHER DOSE OF SSRIs. HOWEVER,
IF AN INDIVIDUAL PATIENT IS NOT ABLE TO
TOLERATE HIGHER DOSE, LOW TO MEDIUM
DOSE TREATMENT CAN BE CONSIDERED.
Duration of trial and dose titration
A recent meta-analysis of 17 RCTs found that SSRIs
separate from placebo as early as 2 weeks and that
majority of improvement occurs early on in the course
of treatment [20]. However, improvements seen early
in the course of treatment may not be always clinically
meaningful. In many patients, clinically meaningful
improvements may be seen only after weeks or months
of treatment. It is recommended that an adequate trial of
a SSRI (or clomipramine) should be at least for 12 weeks
to account for the lag in the onset of action. The APA
guidelines recommend upward titration to the maximum
FDA-approved doses by 4-6 weeks and continuation in that
dose for another 6-8 weeks or so to determine efficacy
[11]. Certain clinical and biological predictors of treatment

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Reddy, et al.: CPGs for OCD

Non-response to 2 adequate trials with SSRIs Given the absence of evidence from placebo-controlled
trials, venlafaxine is not the first-line treatment for OCD.
Hence, the guidelines consider venlafaxine as a second-line
Add CBT/ BT Clomipramine if CBT / BT are not feasible monotherapy agent in the treatment of OCD.
No response
No response Mirtazapine has been studied as a monotherapy in two
Clomipramine BT / CBT
small open-label trials with inconsistent findings. Therefore,
mirtazapine cannot be recommended as monotherapy in
No response
No response treatment of OCD.
Switch to third SSRI Switch to third SSRI
3. Treatment strategy for non-responders to first-line
No response treatment
Definitions of treatment outcome [21] are given in
Add Risperidone or Table 8. Estimates suggest that around 40-70% patients
Aripiprazole to SSRI
show an adequate response to a trial of SSRI with a
No response
remission rate of 10-40% [16]. Clinicians often face the
subsequent challenge of partial and non-response to SSRIs.
Add 5-HT 3 antagonists / memantine / lamotrigine to SSRI
Continuing improvement has been noticed with prolonged
No response trial of SSRIs as discussed above. Hence, the initial trial
may be continued further if there is evidence of ongoing
Try untried SSRI or venlafaxine
improvement. A general treatment algorithm for OCD and
No response for non-responders to SSRIs is shown in Figures1 and 2
Inpatient intensive treatment with CBT / BT + SSRI for severe OCD
respectively.
Try outpatient CBT / BT for second time in mild-moderate OCD

a. Switching to another medication

No response
Switching to another first-line medication has been found
Ultra-high dose SSRIs, addition of clomipramine, rTMS , to be effective; experts provide a rough estimate of 40-
Mirtazapine, N-acetyle cysteine, Ketamine
50% response rate for the second SSRI and decreasing
No response response rates with further trials. Switching to a second
SSRI is suggested for non-responders to a first SSRI. In
DBS, ablative surgery for severe, chronic, treatment refractory OCD
partial responders, changing medication may entail
Figure 2: Strategies for non-responders to SSRIs. SSRI- loss of the response to the earlier medication. Hence,
Selective serotonin reuptake inhibitors, CBT/BT-Cognitive switching is recommended in partial responders only if
behavior therapy/behavior therapy, rTMS- repetitive there are severe persisting symptoms or upon failure of
transcranial magnetic stimulation other augmenting strategies such as CBT and atypical
antipsychotics.
response to SSRIs have been identified but they are not
robust predictors (Table 7). b. Switching / Augmenting with CBT/BT
It is uncertain whether initiating a combination of BT/CBT
GUIDELINES RECOMMEND CONTINUING simultaneously with SSRI is advantageous compared to
MAXIMALLY TOLERATED EFFECTIVE DOSE OF either treatment alone. However, CBT/BT has been proven
A SSRI FOR AT LEAST 12 WEEKS FOR JUDGING to be effective as an augmenter in partial/non-responders
ITS EFFICACY. GUIDELINES ALSO RECOMMEND to SSRIs [18, 22, 23]. Where feasible, CBT/BT is a potential
DOSE ESCALATION TO EFFECTIVE DOSE first-line augmenting option for partial/non-responders to
RANGES WITHIN 4-6 WEEKS AND CONTINUATION SSRI treatment.
IN THE SAME DOSE FOR ANOTHER 6-8 WEEKS.
c. Augmenting with another medication (Table 9)
2. Other medications that can be tried as monotherapy in The following medications have been commonly tried as
OCD augmenters to SSRIs. Atypical antipsychotics, risperidone
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor and aripiprazole have the best evidence.
with preferential serotonergic action, has been studied
in comparison to paroxetine in a double blinded study i Antipsychotics
and clomipramine in a single blinded study. The studies Antipsychotics are the most widely studied augmenting
found no difference in the efficacy between venlafaxine agents of SSRIs [23]. The literature on antipsychotic
and the comparator agents in acute control of OCD. augmentation is fraught with methodological limitations

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Table 8: Definitions of treatment outcome in OCD

Consensus definitions and operationalization of treatment response, partial response, remission, recovery, and relapse for Obsessive‑Compulsive
Disorder (OCD)
Conceptual Definition
TREATMENT RESPONSE A clinically meaningful reduction in symptoms (time,
PARTIAL RESPONSE distress, and interference associated with obsessions,
compulsions, and avoidance) relative to baseline
severity in an individual who meets diagnostic criteria
for OCD
REMISSION The patient no longer meets syndromal criteria for the
disorder and has no more than minimal symptoms.
Residual obsessions, compulsions, and avoidance
may be present but are not time consuming and do not
interfere with the person’s everyday life
RECOVERY The patient no longer meets syndromal criteria for
the disorder and has had no more than minimal
symptoms. Residual obsessions, compulsions, and
avoidance may be present and slightly fluctuate in
severity over time but, overall, they are not time
consuming and do not interfere with the person’s
everyday life and therefore require no further
treatment. The clinician may begin to consider
discontinuation of treatment or, if the treatment
continues, the aim is to prevent relapse
RELAPSE After response or remission or recovery was achieved,
the patient experiences a return of symptoms.
For patients who were in remission or recovered,
obsessions, compulsions, and avoidance are again
sufficiently time consuming, distressing, and
impairing for the individual to meet diagnostic criteria
for OCD
Abbreviations: CGI‑I – Clinical Global Impression Improvement; CGI‑S – Clinical Global Impression Severity; (C) Y‑BOCS – (Children’s) Yale‑Brown Obsessive
Compulsive Scale; OCD – Obsessive-Compulsive Disorder. Ref: [21]. This table is reprinted with permission from the lead author of the Delphi survey. The table is
not part of the publication
Operationalization
A ≥35% reduction in (C) Y‑BOCS scores plus CGI‑I rating of
1 (‘very much improved’) or 2 (‘much improved’), lasting for
at least one week
A ≥25% but <35% reduction in (C) Y‑BOCS scores plus CGI‑I
rating of at least 3 (‘minimally improved’), lasting for at least
one week
If a structured diagnostic interview is feasible, the person no
longer meets diagnostic criteria for OCD for at least one week
If a structured diagnostic interview is not feasible, a score of
≤12 on the (C) Y‑BOCS plus CGI‑S rating of 1 (‘normal, not
at all ill’) or 2 (‘borderline mentally ill’), lasting for at least
one week
If a structured diagnostic interview is feasible, the person no
longer meets diagnostic criteria for OCD for at least one year
If a structured diagnostic interview is not feasible, a score of
≤12 on the (C) Y‑BOCS plus CGI‑S rating of 1 (‘normal, not
at all ill’) or 2 (‘borderline mentally ill’), lasting for at least
one year
For responders who did not necessarily remit/recover: The
person no longer meets the definition of ≥35% reduction
on (C) Y‑BOCS scores (relative to pre‑treatment) plus CGI‑I
rating of 6 (‘much worse’) or higher for at least one month
For remitters/recovered: OCD criteria are met again,
according to a structured interview (if feasible). Alternatively,
the person no longer meets the definition of remission/
recovery (i.e., the person again scores 13 or above on the (C)
Y‑BOCS) plus CGI‑I rating of 6 (‘much worse’) or higher
for at least one month or needs to be withdrawn prematurely
from the trial before one month has elapsed due to a severe
worsening of OCD symptoms. Discontinuation of the trial due
to reasons other than a worsening in OCD symptoms (e.g.,
suicide risk) is not considered a relapse

including small sample sizes, varying doses and duration of
treatment with both antipsychotics and concomitant SSRIs,
varying degree of treatment resistance etc. Two recent
meta-analyses of 14 RCTs on antipsychotic augmentation
found that antipsychotic as a group was significantly more
effective than placebo in decreasing YBOCS scores [24, 25].
About a third of patients responded to antipsychotic
augmentation. Aripiprazole and risperidone are consistently
found to be effective as augmenting agents. The evidence
for haloperidol should be interpreted with caution as it
was based on a single study. A fairly large RCT comparing
CBT, risperidone and pill placebo augmentation of SSRI
found that risperidone did not separate from placebo in
augmenting efficacy [26]. This study has raised questions
on the efficacy of risperidone as an augmenter. Quetiapine
and olanzapine have not been consistently found to be
effective, while other antipsychotics have not been studied
adequately. Meta-analyses do not throw any light on
adequate dose and duration of antipsychotic treatment
[24]. Antipsychotics should be used in low doses (e.g., 1-3 mg
of risperidone, 5-10 mg aripiprazole) for a period of at least
8 weeks for an adequate trial. Use of antipsychotics in the
long-run should be considered after weighing the benefits
and risks of long-term use.
BASED ON THE AVAILABLE EVIDENCE,
ARIPIPRAZOLE AND RISPERIDONE MAY
BE CONSIDERED THE FIRST CHOICE FOR
PHARMACOLOGICAL AUGMENTATION
ii. Glutamatergic agents
There is a strong theoretical rationale supporting the use
of glutamatergic drugs in OCD. The following glutamatergic
agents have been studied in OCD [23]:

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Table 9: Pharmacological augmenting agents in OCD iv. Other augmenting agents

Drug Suggested dosage $ Strength of recommendation* Buspirone, lithium and clonazepam have not been found
Aripiprazole 5‑10 mg A effective and hence are not recommended as augmenting
Risperidone 1‑3 mg A agents. The safety and efficacy of psychostimulants and
Haloperidol 2.5‑10 mg B opioid drugs have to be systematically studied before they
Memantine 10‑20 mg B are recommended for routine clinical use. Intravenous
Lamotrigine 100mg B
ketamine has been found to have acute anti-obsessive
Ondansetron 2‑4 mg twice a day B
Granisetron 1 mg twice a day B effects in a “proof-of-concept” study, which needs
$ ‑ Rough estimate based on available evidence replication and long term evaluation before the strategy can
*Based on modified Strength of Recommendation Taxonomy (SORT)[15] be recommended for routine clinical use.
A – Consistent, good‑quality patient‑oriented evidence i.e., Meta‑analysis of
Randomized controlled trials (RCT) with consistent findings or high quality
individual RCT B – Inconsistent or limited‑quality patient‑oriented evidence d. Other experimental strategies
i.e., systematic review/meta‑analysis of lower quality clinical trials or studies While there appears to be some short-term benefits for
with inconsistent findings/lower quality clinical trial/cohort study/case‑control
study C – Consensus based clinical guidelines extrapolations from bench intravenous clomipramine in treatment resistant patients,
research, disease‑oriented evidence, usual practice, opinion, case‑series the long term benefits are uncertain. This formulation is
not available in India and is not recommended at present
a. Memantine: found effective in 2 double blinded and for clinical use. There are a few uncontrolled trials
one single blinded RCT. demonstrating the utility of higher than recommended
b. Lamotrigine: found effective in 2 double blinded RCTs doses of SSRIs (up to 400 mg of sertraline, 40-50 mg of
c. Topiramate: effective in 2 small double-blind RCTs, but escitalopram) in resistant patients. This strategy should be
poorly tolerated considered experimental and may be used only in resistant
d. Riluzole: inconsistent results in two RCTs patients after exhausting other regular safer options.
e. N-acetylcysteine: conflicting results from three RCTs,
has to be studied further. ROLE OF OTHER NON-SOMATIC TREATMENTS

BASED ON THE EVIDENCE AND ITS RELATIVELY Around 20% of patients do not respond to available
BETTER TOLERABILITY, MEMANTINE IS pharmacological and psychological treatments.
PREFERRED OVER LAMOTRIGINE AS THE Neuromodulatory and neurosurgical treatments targeting
FIRST CHOICE GLUTAMATERGIC AUGMENTING the cortico-striato- thalamo-cortical (CSTC) circuits have
AGENT. been tried in resistant patients.

iii. Serotonergic agents NON-INVASIVE BRAIN STIMULATION

5HT-3 antagonists including ondansetron and granisetron
are reported to be effective and well tolerated in small RCTs
[27]. However, due to the methodological limitations of the
individual studies, 5HT-3 antagonists are recommended as
second line augmenting agents along with glutamatergic
agents.
Preliminary evidence suggests that clomipramine can
be an effective augmenting agent. Clomipramine and
SSRI combination should be used cautiously, especially
with fluoxetine and fluvoxamine, as they may increase
clomipramine related adverse effects (including serious
events like seizures, cardiac effects, serotonin syndrome)
due to pharmacokinetic interactions. Clomipramine
augmentation of SSRI may be tried but adequate precautions
need to be taken keeping in mind the potential adverse
effects of the combination.
Mirtazapine augmentation has been found to hasten the
response with no significant long term benefits [23] and
hence may be considered as an augmenting agent in partial
responders and non-responders.
TECHNIQUES
1. Electroconvulsive therapy(ECT)
ECT has not been systematically evaluated for the treatment
of OCD. Available evidence, in the form of case reports and
case series, do not provide evidence for the efficacy of ECT
[28]. Hence, ECT is not recommended as a treatment for
OCD and may be considered for the treatment of comorbid
conditions like severe mood and psychotic disorders, if
indicated.
2. Repetitive transcranial magnetic stimulation (rTMS)
rTMS entails the possibility of non-invasive and focal
stimulation of superficial cortical regions, thereby
increasing or decreasing their excitability based on the
frequency of stimulation. The regions implicated in OCD
are usually not accessible with available technology of
rTMS. Hence rTMS has been tried in superficial cortical
regions which have connections with other deeper
structures implicated in OCD. Controlled trials of low
frequency or high frequency rTMS over either dorsolateral
prefrontal cortex (DLPFC) have yielded conflicting results

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but low frequency rTMS over supplementary motor area
(SMA) and orbitofrontal cortex (OFC) appear promising
[29]. However, the evidence has not been very consistent.
Overall, the findings have to be replicated in larger
samples with long term follow-up. There is no convincing
evidence that beneficial effects persist for longer than
the trial period. The guideline recommends rTMS as an
intervention for further research and not for routine
clinical use.
3. Transcranial direct current stimulation (tDCS)
tDCS is another focal and superficial cortical modulatory
intervention, which either increases or decreases the
excitability of the underlying cortex depending on the
polarity of the stimulating electrode. There are only a few
case reports and an open-label trial on tDCS in OCD. It
has to be evaluated more systematically before it can be
recommended for clinical use in OCD.
NEUROSURGICAL PROCEDURES
1. Ablative neurosurgery
Ablative neurosurgical procedures involve producing lesions
in specific regions of the CSTC circuit, which is hypothesized
to be dysfunctional in OCD. Reliable lesions can be produced
with the help of “invasive” stereotactic surgery or “non-
invasively” with the help of image guided gamma radiation.
Anterior cingulotomy and a refined version of capsulotomy
known as ‘gamma ventral capsulotomy’ are practiced
in treatment refractory OCD in a few centers. Due to the
irreversible nature, these procedures are generally employed
in treatment refractory patients (Table 10). Evidence primarily
in the form of uncontrolled studies suggests that around 40-
Table 10: Selection criteria for surgery
1. Severe (YBOCS >28) and chronic unremitting OCD
2. The disorder is causing substantial distress and impairment in
functioning (GAF ≤45)
3. The following treatment options tried systematically without appreciable
effect on the symptoms
• Adequate trial with at least 2 of the SSRI antidepressants for at least 3
months each
• Treatment with clomipramine at optimum dosage for at least 3 months
unless poorly tolerated
• Augmentation with at least 2 agents, one of them being an atypical
antipsychotic: atypical antipsychotic (ripseridone, aripiprazole),
clomipramine, memantine, ondansetron/granisetron
• At least one adequate trial of cognitive behavior therapy (at least 20
sessions of exposure and response prevention) or demonstrated inability
to tolerate the anxiety due to therapy
• Previous treatment trials have not been abandoned prematurely due to
solely mild side effects
4. Patient gives informed consent
5. Willing to participate in the pre‑operative evaluation and post‑operative
periodic follow‑up
Relative contraindications:
1. Comorbid intellectual disability, psychosis, bipolar disorder and severe
personality disorders
2. Clinically significant and unstable neurologic illnesses
Indian J Psychiatry 59 (Supplement 1), January 2017
60% of patients improve over 6-24 months following surgery.
There is some suggestion that capsulotomy may be more
effective procedure in OCD [30] and that its efficacy may be
similar to that of deep brain stimulation (DBS)[31]. Surgery
may be associated with short-term and persistent adverse
effects including personality changes, seizures and cognitive
adverse effects although rates are not high.
2. Deep brain stimulation
Deep brain stimulation (DBS) is a potentially reversible
procedure involving high frequency stimulation of
implanted electrodes in the brain. Although the mechanism
of action is poorly understood, it is hypothesized to modify
dysfunctional circuits. DBS for OCD has been evaluated
in sham controlled studies targeting nucleus accumbens,
ventral capsule/ventral striatum, anterior limb of internal
capsule, ventral caudate and subthlamic nucleus. A recent
meta-analysis found a responder rate of 60% with a mean
YBOCS reduction of around 45% [32]. DBS is an invasive
procedure and is associated with short term and long term
adverse effects. Further, the battery needs to be replaced
periodically which may be quite expensive. DBS can be
recommended in carefully selected refractory OCD patients
(Table 10) after discussion regarding the pros and cons of
the procedure.
The neurosurgical procedures are not curative in nature
and the procedures are only one aspect of a comprehensive
treatment program which should continue following
surgery.
Surgical procedures may be considered only in selective
patients after careful evaluation of patients for treatment
refractoriness, severity of illness and comorbidities.
Patients should be explained about the realistic possibility
of benefits and risks. They should be evaluated by an
independent team consisting of a psychiatrist, a neurologist
and a neurosurgeon for suitability for surgery. The treatment
should be conducted under close collaboration of a team
of psychiatrist, neurosurgeon, radiotherapist, imaging
specialist and psychologist with close monitoring of adverse
effects. Suggested criteria for suitability to undergo surgery
are shown in Table 10.
PSYCHOLOGICAL TREATMENTS FOR OCD
(TABLE 11)
A. Cognitive Behavioral Therapy (CBT) / Exposure
and Response Prevention (ERP)
Consistently, CBT/ERP has been shown to be efficacious in
the treatment of OCD [33]. All treatment guidelines have
suggested the use of CBT as a first-line treatment option.
CBT for OCD includes ERP.
CBT/ERP is a first-line treatment option for OCD. ERP is
the most important component of CBT along with belief
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Table 11: Psychotherapy in OCD
Psychotherapy Strength of
recommendation
Cognitive behaviour therapy (including exposure A Where resources are available, 15-20 hours of therapist
and response prevention)
Behaviour therapy (exposure and response A and computerized CBT is very preliminary and it may be
prevention)
Mindfulness based cognitive behaviour therapy C
Acceptance and commitment therapy C
Stress management and relaxation training C
Thought stopping C B. Other Psychological therapies
Dynamic psychotherapy C 1. Acceptance and Commitment Therapy
*Based on modified Strength of Recommendation Taxonomy (SORT)[15]
modification. When facilities are available, CBT/ERP
monotherapy may be recommended in mild to moderately
ill patients. In severely ill patients a combination of CBT and
SSRI is recommended.
CBT as an augmentation strategy
It is uncertain whether initiating a combination of CBT/ERP
and SSRI is advantageous compared to either treatment
alone. However, CBT/BT is found to be effective in
augmenting SSRIs in partial/non-responders to SSRIs [34].
A recent study found CBT to be superior to risperidone and
placebo in augmenting SSRIs in OCD [35]. Patients in the CBT
group had significantly greater reductions in OCD symptom
severity compared with participants taking risperidone or
placebo. Risperidone was not superior to placebo on any
outcome measures.
When facilities for CBT are available, CBT / BT is
recommended as the first line augmenting strategy in
partial/non-responders to SSRI treatment.
Mode of CBT/ERP delivery and adaptations
Although various models are available for CBT in OCD,
the major components are psychoeducation, development
of symptom hierarchy, cognitive restructuring and ERP
(Table 12). The method of conducting ERP has been found
to be important with ‘therapist–assisted’ ERP producing
a greater change in symptom severity. Therapist-guided
exposure is better than self-guided exposure. The numbers
of CBT sessions have varied between 12 and 20 sessions
across various studies. It has ranged from intensive daily 2
hour sessions for 5 days a week for 3 weeks to less intensive
twice weekly sessions in other studies.
Even though group CBT has been compared with individual
CBT, the results have been mixed. While a couple of
studies have reported comparable efficacy for group and
individual forms of CBT, some other studies demonstrated
the superiority of individual mode of CBT compared to
the group CBT. Another adaptation of CBT which has
been examined in the recent years is the internet based
CBT (ICBT) and computerized CBT. They are found to be
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effective compared to supportive therapy / relaxation
methods [36, 37].
assisted CBT / BT may be considered. The evidence for ICBT
recommended in certain circumstances where regular face-
to-face CBT is not feasible.
This therapy aims to improve psychological flexibility
through the practice of acceptance and mindfulness in
addition to commitment and behavior modification exercises.
Preliminary evidence suggests its benefits but it needs to be
tested and compared with CBT in larger samples.
2. Stress management and relaxation training
These have been conventionally used in many studies
as control arm in studies CBT. Stress management and
relaxation training may have non-specific effects but there is
no evidence suggesting their efficacy in treatment of OCD.
3. Mindfulness based cognitive therapy
Mindfulness based therapy is thought to be useful in
OCD. Preliminary data suggests its utility in treating OCD.
Protocols for RCT are published but there is no published
evidence in the literature in clinical population.
4. Family inclusive treatments
Family-inclusive treatment (FIT) approaches aim to include
the family members in the treatment so as to improve
the family functioning, facilitate behavioral therapy etc.
Studies targeting family accommodation of obsessive-
compulsive symptoms report greater improvements in
patient functioning. Family members may be encouraged to
participate in CBT since family accommodation of symptoms
is associated with poorer treatment outcomes.
5. Others
The other forms of psychological therapies with isolated
studies include adjunct motivational interviewing to ERP
and Eye Movement Desensitization and Reprocessing
(EMDR). There is one study examining the role of brief
dynamic therapy in OCD with negative result. In addition,
the potential benefits of adding D-cycloserine prior to ERP
sessions has been examined in few studies.
MANAGEMENT AS PER THE DIFFERENT PHASES
OF ILLNESS
Acute phase
This includes decision on choice of treatment modality
(SSRI vs. CBT), implementation of treatment, monitoring for
the response and side-effects, and planning for sequential
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Table 12: Components of CBT for OCD

Step
Assessment
Psychoeducation
Formulate the therapy
Handling the thoughts
Challenging the dysfunctional
beliefs
Behavioral Experiments-Exposure
and Response prevention
Relapse prevention
Components
• Assess nature and severity of OCD symptoms (YBOCS symptom checklist and severity rating)
• Examine insight in to the OCD symptoms
• Assessment of safety behaviors and avoidance strategies employed by the patient
• Look for current comorbid conditions such as depression that may interfere with CBT
• Assess the motivation levels and personality attributes of the patient
• Family’s involvement (accommodating the symptoms, proxy compulsions, expressed emotions) needs to be
explored
• Educate regarding the nature of obsessions and compulsions
• Explain the cycle of propagation of obsessions through performing compulsions and by avoiding the stimuli
• Discuss in detail the rationale behind CBT (concepts of habituation, fear extinction and the role of
dysfunctional beliefs)
• Educate the family members about principles in CBT
• Formulation needs to be personalized
• Identify the specific cognitive distortions (maladaptive thinking patterns) such as exaggerated threat
perception, inflated responsibility, perfectionism, need to control thoughts etc.
• Develop a collaborative understanding of the formulation with the patient (e.g., the goal is to eliminate fear of
• HIV infection and not reduce/prevent the chances of contracting HIV)
• Explain the “neutral spectatorship” principle towards obsessions (don’t interpret them, observe )
• Demonstrate how offering active resistance to obsessions is counterproductive and increases their salience
• Foster the practice of gathering evidence for the thoughts (how likely would it happen/what is the worst
consequence/less threatening alternative explanations etc.)
• Socratic questioning initiated
• Examining the faulty appraisals with examples
• Preparing for behavioral experiments (exposure and response prevention)
• ERP forms the core of CBT. Exposure to anxiety provoking situations in a graded manner with negotiations
and contracts at every step
• Rationale of ERP with examples-explain the habituation and extinction principle with the aim of anxiety
reduction as well as disconfirmation of the fears
• Make a list of anxiety provoking situations/triggers in a hierarchical manner using subjective units of
distress (0 to 10 subjective rating by the patient)
• Expose the patient starting from the lowest anxiety provoking situation and gradually escalate the level. Each
session lasting for 1‑1 ½ hours , till the patient experiences reduction in distress/anxiety
• Homework assignments, consistent performance of ERP tasks insisted upon
• Explain that treatment is a continuous process
• Periodic booster sessions to review the situation and to troubleshoot emerging issues
• Anticipation of future concerns such as change in the form of symptoms, relapse under stress, emergence of
subtle avoidance behaviors etc
• Encourage regular work and other normal behaviors

treatment trials if initial treatments failed to produce MANAGEMENT OF COMORBID CONDITIONS

satisfactory improvement.
Maintenance treatment (How long the treatment should
be continued?)
There is evidence for ongoing improvement with continued
use of SSRIs and clomipramine in long term continuation
studies for a period of up to 1 year[18]. Guidelines
recommend continuation of SSRIs / clomipramine for at
least 1-2 years after achieving remission. Clinical experience
dictates that discontinuation of medication beyond that
period may be associated with increased chance of relapse.
Hence discontinuation of medications should be carefully
considered based on individual patient factors including
severity and duration of illness, past history of relapse on
discontinuation, residual symptoms, comorbidities etc.
Most patients may require continued pharmacotherapy to
prevent relapses. Medications are generally recommended
to be continued at the same dose that resulted in
improvement, unless the dosage is not tolerated.
Depression and Anxiety disorders
Most common co-occurring illness is major depression. The
Pharmacological treatment strategy does not change much,
however in severe depression CBT/ERP for OCD needs to
kept on hold until the patient recovers from depression.
Severe depression with prominent suicidal ideas needs
to be evaluated thoroughly and ECT may be considered if
indicated. Comorbid dysthymia is common and may require
individual therapy.
Comorbid anxiety disorder needs to be treated aggressively
since untreated anxiety disorder may contribute to poor
treatment outcome. Comorbid anxiety disorders may
require CBT in addition to SSRIs.
Tic disorders
Tic disorders show best response to antipsychotics
(haloperidol, pimozide, risperidone and aripirazole).

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Although antipsychotics may be more effective, adrenegic α2
agonists (clonidine and guanafacine) may be tried first to treat
tics in view of adverse effects associated with antipsychotics.
Habit-reversal therapy (HRT) is a potential first-line treatment
option instead of or in combination with pharmacotherapy.
OCD patients with tic disorders may require a combination
of an SSRI and an antipsychotic. There is evidence that OCD
comorbid with tic disorders may not respond satisfactorily
to SSRI alone.
Bipolar Disorder
Comorbid bipolar disorder calls for a different treatment
strategy because SSRIs are well known to cause/exacerbate
hypomania or mania. Mood stabilization should be the
primary goal in treating OCD-bipolar patients [38]. In
many patients with comorbid bipolar disorder, OCD often
manifests / increases in severity in depressive episodes but
improves in mania / hypomania episodes. In such patients,
treatment with mood stabilizer alone may be considered.
If OCD persists outside of the mood episodes, CBT may be
preferred over SSRIs. However, if patient requires an SSRI,
it has to be prescribed under the cover of mood stabilizers
or an atypical antipsychotic.
Psychosis
OC symptoms and OCD are not uncommon in those with
schizophrenia; up to 25% of the schizophrenia patients
report clinically significant OCD symptoms. SSRIs may be
used in treating OCD comorbid with schizophrenia, but there
is limited published evidence. Some atypical antispychotics
such as clozapine, risperidone and olanzapine may induce
or even worsen OCD symptoms. In case of drug-induced OC
symptoms, if feasible, one may consider reducing dose or
changing to another antipsychotic.
Personality disorders
20% of the participants suffer from at least one comorbid
personality disorder (PD). The most common are obsessive-
compulsive, narcissistic and anxious avoidant personality
disorders. Presence of PD can complicate the course and
outcome. OCD patients with different comorbid PDs differ
in their therapeutic response to treatment. Borderline,
obsessive-compulsive and schizotypal personality disorders
can contribute to poor outcome. There are no systematic
studies comparing the effects of treatment in OCD coexisting
with PD. Generally it is agreed upon that a combination of
medications, CBT-ERP and individual therapy are advocated.
OCD during pregnancy and lactation
Medication should be guided primarily by its safety data,
severity of the illness, and benefit vs. risk to the developing
fetus. For newly diagnosed OCD during pregnancy and in
the post-partum period, CBT/ERP is the preferred option
[39]. Pre-pregnancy counseling for all women should
include planning pregnancy, folate supplementation,
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discussion with patient and spouse regarding options,
and active liaison with obstetricians, ultrasonologists and
pediatricians.
Following is the summary of SSRIs in pregnancy and lactation:
1. If the patient is symptom-free for a long period, an
attempt may be made to withdraw the SSRI gradually.
However, a risk of relapse following discontinuation
should be discussed.
2. Benefits vs. risks of continuing SSRIs during pregnancy
should be discussed keeping in mind the fact that OCD
can relapse following discontinuation.
3. SSRIs as a group do not appear to be major teratogens.
4. SSRIs, paroxetine in particular have been associated with
increased risk for cardiac malformations (septal defects)
(1.5-2%), as compared to the general population (1%)
but the evidence is inconsistent. Paroxetine may be
avoided; it is less safe than the other SSRIs.
5. Some studies have reported an association between SSRI
use in first trimester and anencephaly, craniosynostosis,
and omphalocele. However, it must be emphasized that
the risks are rare and absolute risks are small.
6. When taken in late pregnancy, SSRIs may increase the
risk of persistent pulmonary hypertension by more
than twofold in the newborn (absolute risk, 3 infants
per 1000 exposed vs. 1.2 infants per 1000 unexposed).
7. SSRIs have also been associated with decreased
gestational age, low birth weight and spontaneous
abortion
8. Following birth, serotonergic toxicity and antidepressant
discontinuation symptoms may manifest, therefore it is
important to liaise with pediatricians.
9. Sertraline, fluvoxamine and paroxetine are present in
very low concentrations in plasma of breast-fed infants
(<3% of maternal dose). It is surmised that they are
relatively safe during breast feeding. With fluoxetine
and citalopram, infants can receive up to 15% of the
maternal dose.
OCD in child and adolescent population
SSRIs and clomipramine are efficacious in treating OCD and
are superior to placebo with modest effect size [40]. CBT
has superior efficacy compared to SSRIs in children [40]. A
combination of CBT and SSRI seems to have no additional
advantage over CBT alone indicating that SRI treatment
adds little to concomitant CBT. However, combined
treatment is better than SSRI alone. In partial responders to
SSRIs, adding CBT is superior and efficacious as compared
to continuing a SSRI. In view of superior efficacy of CBT,
many guidelines advocate CBT as the first line treatment
in children. In children, where facilities are available, CBT
may be preferred over SSRIs as the first-line treatment. In
children with severe OCD, a combination of CBT and SSRI
is recommended over SSRI alone. SRIs are the alternative
first-line treatment for OCD in children in situations where
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Table 13: Side‑effects of SSRIs

Somnolence Comment Management
Drowsiness, All SSRIs can cause somnolence Drowsiness: Prescribe bulk of dose at bedtime
insomnia Insomnia more common with fluoxetine Insomnia: Fluoxetine may be prescribed in the morning.
Benzodiazepines, Trazadone or zolpidem may be used for
insomnia
Hypotension Not a usual side‑effect
Conduction SSRIs have no effect on QTc and are not associated with SSRIs are generally safe in patients with cardiovascular
disturbances arrhythmias and conduction disturbances diseases including the post myocardial infarction period
Exception: Citalopram (? escitalopram) is associated with dose Sertraline appears to be the safest. Citalopram and escitalopram
related increase in QTc and Tosades de pointes in overdose should be used with caution in those at risk for arrhythmia
Anticholinergic Not prominent with SSRIs except with paroxetine Most get over the side‑effects. If they are troublesome, reduce
the dose or change the SSRI
Gastrointestinal Nausea, vomiting, diarrhea, dyspepsia and anorexia are common. Common GI side‑effects usually settle down with continued
Nausea more common with Fluvoxamine. Paroxetine can cause use. If they persist, reduce dose or change the SSRI. Proton
constipation pump inhibitors may be useful
SSRIs may increase the risk of gastrointestinal bleeding Use SSRIs with caution when co‑administered with aspirin,
NSAIDs or oral anticoagulants
Neurological Headache (and worsening of migraine), tremors and rarely Fine tremors, akathisia may respond to propranolol.
akathisia, extrapyramidal symptoms, seizures and dyskinesias Extrapyramidal symptoms respond to trihexiphenidyl.
Headache responds to acetaminophen prn
Activation/ Usually seen with fluoxetine Increase the dose gradually; benzodiazepines may help
agitation
Switch to mania/ Risk of switch to mania/hypomania is known in those with bipolar Always use under the cover of mood stabilizers or atypical
hypomania disorder antipsychotics
Sexual All SSRIs are associated with sexual dysfunction; prevalence may Identify if other causes such as depression and medical causes
dysfunction be as high as 60% are contributing to sexual dysfunction
All phases of sexual response are affected including decreased If possible, reduce dose or employ drug holidays but this
libido, erectile dysfunction, decreased vaginal lubrication, delayed approach has the risk of relapse
orgasm, and ejaculatory delay. Erectile dysfunction and ejaculatory Change to other SSRI may be considered
delay are worse with paroxetine compared to other SSRIs Siddenafil or tadalafil, cyproheptadine, and bupropion may
improve sexual dysfunction
Hyponatremia SSRIs are associated with hyponatremia because of syndrome of Hyponatremia is common in elderly. Monitoring is essential.
inappropriate secretion of antidiuretic hormone (SIADH). Risk Referral to specialists if serum level is <125 mmol/L
factors include old age, female gender, co‑administration of drugs
known to cause hyponatremia (diuretics, NSAIDs, ACE inhibitors
etc), reduced glomerular filtration rate, and medical comorbidity
Serotonin Nausea, vomiting, diarrhea, tremor, sweating, disorientation, Stop the offending drugs immediately. Symptomatic
syndrome restlessness, agitation, headache, increased heart rate, changes in management: benzodiazepines to treat agitation and/
blood pressure & temperature, twitching, tremors, myoclonic jerks, or seizures, intravenous fluids to maintain hydration,
hyperreflexia, high fever, seizures, arrthymias, agitation, confusion, anti‑emetic and anti‑pyretic medications. In severe cases,
delirium and even coma cyproheptadine (8‑12mg/day) is given orally
Can occur with very high doses of SSRIs or a combination of
SSRIs in high doses
Weight gain Known with all SSRIs although there may be initial weight loss. If weight gain is significant, an attempt may be made to shift to
Paroxetine is associated with weight gain more than other SSRIs another SSRI
Lifestyle modification may be discussed
Drugs such as topiramate may be tried
Suicidal SSRIs are associated with increased suicidal ideation and attempts Children on SSRIs should be monitored closely for emergence
behavior in children of suicidal thoughts
Discontinuation Abrupt discontinuation may cause discontinuation syndrome, Withdraw gradually. Taper SSRI by no more than 25% per
syndrome particularly with short‑acting drugs (dizziness, nausea, vomiting, week
diarrhea, headache, fever, sweating, chills, insomnia, paresthesias,
electric‑shock‑like sensations, anxiety, agitation, irritability,
disorientation). Reported mostly with paroxetine. Typically occur
within a week of discontinuation
Drug Fluoxetine, paroxetine and fluvoxamine inhibit cytochrome P‑450. Caution should be exercised in combining ceratin SSRIs
interactions Inhibit the metabolism and elevate levels of drugs metabolizedd by with drugs that are essentially metabolized by cytochrome
this system P‑450 system. SSRIs can elevate clomipramine level resulting
in more side effects, particularly seizures and serotonin
syndrome; this combination should be used judiciously and
patients have to be monitored closely

CBT is either not available or the child cannot comply with SSRIs in medically ill
CBT. SSRIs are generally safe in patients with cardiovascular

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Reddy, et al.: CPGs for OCD
Table 14: Summary of treatment recommendations
• Establish a diagnosis of OCD. Assess for comorbid conditions such as
depression and anxiety disorders and certain personality disorders. It is
important to treat comorbid conditions since untreated comorbidity may
contribute to poor outcome
• Where feasible, employ instruments such as the YBOCS to assess
symptoms and their severity
• Psychoeducation of the patient and family about OCD, its course and
treatment options is essential
• SSRIs and CBT are the first‑line evidence based treatment options for
OCD. In the Indian context, SSRIs are often the preferred first‑line
treatment options
• All SSRIs are equally effective but they differ in their side‑effect profile.
Choice of an SSRI for an individual patient is based on factors such as
previous response, tolerability, acceptability, adverse effects, cost and
drug interactions
• Most patients require higher than the usual antidepressant dose of an SSRI
• There is no convincing evidence that clomipramine is superior to SSRIs.
Since clomipramine has many side‑effects, it is not recommended as the
first‑line treatment option. It may be considered if patient fails to respond
to 2 or more SSRIs
• An adequate trial of an SSRI (or clomipramine) should be for at
least 12 weeks in optimum doses. Premature discontinuation is not
recommended since most patients show improvement gradually over
several weeks
• SSRI has to be continued at least for 1‑2 years after remission However,
most patients may require indefinite continued treatment with a SSRI to
prevent relapses particularly those with severe and chronic illness, past
history of relapse on discontinuation and clinically significant residual
symptoms. SSRIs are generally recommended to be continued at the same
dose that resulted in improvement, unless the dose is not tolerated
• CBT alone may be recommended in mild to moderately ill patients if
facilities for CBT exist. However, most severely ill patients benefit from a
combination of an SSRI and CBT
• In partial responders and non‑responders to SSRIs, addition of CBT
is recommended as the first option. If CBT is not feasible, an atypical
antipsychotic in low dose (risperidone and aripiprazole) may be added as
an augmenting agent
• Inpatient treatment is recommended for severely ill, treatment
resistant patients and for comorbid conditions such as severe
depression
• ECT has no proven value in the treatment of OCD. There is inconsistent
evidence regarding the efficacy of rTMS; hence it is not recommended for
routine use
• DBS and ablative surgery may be considered in chronic, severely ill
treatment refractory OCD patients
problems. Citalopram (? Escitalopram) is associated with
arrhythmias but the risk is low and may not be clinically
significant, but may be used with caution or avoided in
those at risk for arrhythmias. SSRIs are widely used to
treat depression in diabetes. They may improve diabetic
parameters: improvement in HbA1c levels, reduced insulin
requirement, enhanced insulin sensitivity and improved
glycemic control. SSRIs are not hepatotoxic, but they
need to be used in lower doses and with caution in the
presence of significant hepatic impairment since all SSRIs
are biotransformed in liver. All SSRIs are metabolized by
the Cytochrome P450 system and fluoxetine, fluvoxamine,
and paroxetine also significantly inhibit P450 enzymes.
Therefore, these agents may potentially interfere with wide
variety of other medications. Interactions with other drugs
S88
need to be considered, particularly in elderly who are likely
to be on many medications for other medical conditions.
Citalopram / escitalopram and sertraline do not substantially
inhibit P450 enzymes and therefore are associated with less
drug interactions. All SSRIs are renally excreted. Depression
is common in those with chronic kidney disease (CKD)
and end stage renal disease (ESRD). If indicated SSRIs are
the preferred antidepressants. SSRIs such as paroxetine,
citalopram and escitalopram may have to be administered
in lower doses in CKD and ESRD in the background of
compromised renal functions. Since many patients with
CKD and ESRD also suffer from cardiovascular disorders,
citalopram (and perhaps escitalopram) may be used with
caution since high doses of citalopram is associated with
QTc prolongation and torsades de pointes.
Side Effects of SSRIs
The dosage of anti-obsessive drugs is usually higher than
the usual anti-depressant dose; hence it is important for
the clinician to discuss regarding the common side-effects.
This issue is important because patients need to be on
medications for a long duration. Sometimes an adjustment
in dose or a switch in the time of the day the dose is taken is
all that is needed. Rarely, stopping a particular medication
and switching to another medication may be required. Side-
effects of SSRIs and possible remedies are given in Table 13.
Summary
Recommendations are summarized in Table 14. The SSRIs
and CBT are the first-line treatment options for OCD. CBT
alone may be tried in mild to moderately ill patients if
facilities for CBT are available. In severe OCD, a combination
of SSRI and CBT is recommended. In the Indian context,
SSRIs are the preferred first-line treatment for OCD because
of limited resources for delivering CBT. SSRIs are effective,
well tolerated and safe. For partial responders and non-
responders to SRIs, CBT is an effective augmenting agent
followed by atypical antipsychotics. Although an attempt
may be made to taper and stop SSRI after 1-2 years of
sustained remission, most patients may require indefinite
continued treatment with a SSRI. DBS and ablative
surgery may be considered in chronic, severe OCD if other
established treatment options have failed to produce any
clinically significant improvement.
REFERENCES
1. Ruscio AM, Stein DJ, Chiu WT, Kessler RC (2010): The epidemiology
of obsessive-compulsive disorder in the National Comorbidity Survey
Replication. Molecular Psychiatry. 15:53-63.
2. Sharma E, Thennarasu K, Reddy YC (2014): Long-term outcome of
obsessive-compulsive disorder in adults: a meta-analysis. The Journal of
Clinical Psychiatry. 75:1019-1027.
3. Simpson HB, Reddy YC (2014): Obsessive-compulsive disorder for ICD-
11: proposed changes to the diagnostic guidelines and specifiers. Revista
Brasileira de Psiquiatria. 36 Suppl 1:3-13.
4. Stein DJ, Kogan CS, Atmaca M, Fineberg NA, Fontenelle LF, Grant JE,
et al. (2016): The classification of Obsessive-Compulsive and Related
Indian J Psychiatry 59 (Supplement 1), January 2017
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Reddy, et al.: CPGs for OCD
Disorders in the ICD-11. Journal of Affective Disorders. 190:663-674.
5. Amerio A, Odone A, Liapis CC, Ghaemi SN (2014): Diagnostic validity
of comorbid bipolar disorder and obsessive-compulsive disorder: a
systematic review. Acta Psychiatrica Scandinavica. 129:343-358.
6. Zutshi A, Reddy YC, Thennarasu K, Chandrashekhar CR (2006):
Comorbidity of anxiety disorders in patients with remitted bipolar disorder.
European Archives of Psychiatry and Clinical Neuroscience. 256:428-436.
7. Shashidhara M, Sushma BR, Viswanath B, Math SB, Janardhan Reddy YC
(2015): Comorbid obsessive compulsive disorder in patients with bipolar-I
disorder. Journal of Affective Disorders. 174:367-371.
8. Mahasuar R, Janardhan Reddy YC, Math SB (2011): Obsessive-
compulsive disorder with and without bipolar disorder. Psychiatry and
Clinical Neurosciences. 65:423-433.
9. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL,
Hill CL, et al. (1989): The Yale-Brown Obsessive Compulsive Scale.
I. Development, use, and reliability. Archives of General Psychiatry.
46:1006-1011.
10. Scahill L, Riddle MA, McSwiggin-Hardin M, Ort SI, King RA, Goodman WK,
et al. (1997): Children’s Yale-Brown Obsessive Compulsive Scale: reliability
and validity. Journal of the American Academy of Child and Adolescent
Psychiatry. 36:844-852.
11. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB, American
Psychiatric A (2007): Practice guideline for the treatment of patients with
obsessive-compulsive disorder. The American Journal of Psychiatry.
164:5-53.
12. Baldwin DS, Anderson IM, Nutt DJ, Allgulander C, Bandelow B,
den Boer JA, et al. (2014): Evidence-based pharmacological treatment
of anxiety disorders, post-traumatic stress disorder and obsessive-
compulsive disorder: a revision of the 2005 guidelines from the British
Association for Psychopharmacology. Journal of Psychopharmacology.
28:403-439.
13. National Collaborating Centre for Mental Health(UK). (2006): Obsessive-
Compulsive Disorder: Core Interventions in the Treatment of Obsessive-
Compulsive Disorder and Body Dysmorphic Disorder, National Institute for
Health and Clinical Excellence: Guidance. British Psychological Society,
Leicester (UK).
14. Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ, Wfsbp Task
Force on Treatment Guidelines for Anxiety O-C, et al. (2008): World
Federation of Societies of Biological Psychiatry (WFSBP) guidelines for
the pharmacological treatment of anxiety, obsessive-compulsive and post-
traumatic stress disorders - first revision. The world journal of biological
psychiatry : the official journal of the World Federation of Societies of
Biological Psychiatry. 9:248-312.
15. Ebell MH, Siwek J, Weiss BD, Woolf SH, Susman J, Ewigman B, et al.
(2004): Strength of recommendation taxonomy (SORT): a patient-centered
approach to grading evidence in the medical literature. The Journal of the
American Board of Family Practice / American Board of Family Practice.
17:59-67.
16. Skapinakis P, Caldwell DM, Hollingworth W, Bryden P, Fineberg NA,
Salkovskis P, et al. (2016): Pharmacological and psychotherapeutic
interventions for management of obsessive-compulsive disorder in adults:
a systematic review and network meta-analysis. The Lancet Psychiatry.
3:730-739.
17. Fineberg NA, Reghunandanan S, Brown A, Pampaloni I (2013):
Pharmacotherapy of obsessive-compulsive disorder: evidence-based
treatment and beyond. The Australian and New Zealand Journal of
Psychiatry. 47:121-141.
18. Arumugham SS, Reddy YC (2014): Commonly asked questions in
the treatment of obsessive-compulsive disorder. Expert Review of
Neurotherapeutics. 14:151-163.
19. Bloch MH, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger
C (2010): Meta-analysis of the dose-response relationship of SSRI in
obsessive-compulsive disorder. Molecular Psychiatry. 15:850-855.
20. Issaria Y, Jakubovski E, Bartley CA, Pittenger C, Bloch MH (2016):
Early onset of response with selective serotonin reuptake inhibitors in
obsessive-compulsive disorder: a meta-analysis. The Journal of Clinical
Psychiatry. 77:e605-611.
21. Mataix-Cols D, Fernandez de la Cruz L, Nordsletten AE, Lenhard F,
Isomura K, Simpson HB (2016): Towards an international expert consensus
for defining treatment response, remission, recovery and relapse in
obsessive-compulsive disorder. World psychiatry : official Journal of the
World Psychiatric Association. 15:80-81.
22. Albert U, Aguglia A, Bogetto F, Cieri L, Daniele M, Maina G, et al. (2012):
Effectiveness of cognitive-behavioral therapy addition to pharmacotherapy
in resistant obsessive-compulsive disorder: a multicenter study.
Psychotherapy and Psychosomatics. 81:383-385.
23. Arumugham SS, Reddy JY (2013): Augmentation strategies in obsessive-
compulsive disorder. Expert Review of Neurotherapeutics. 13:187-202;
quiz 203.
24. Dold M, Aigner M, Lanzenberger R, Kasper S (2015): Antipsychotic
Indian J Psychiatry 59 (Supplement 1), January 2017
Augmentation of Serotonin Reuptake Inhibitors in Treatment-Resistant
Obsessive-Compulsive Disorder: An Update Meta-Analysis of Double-
Blind, Randomized, Placebo-Controlled Trials. The international journal
of neuropsychopharmacology / official scientific journal of the Collegium
Internationale Neuropsychopharmacologicum. 18.
25. Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J
(2014): Atypical antipsychotic augmentation in SSRI treatment refractory
obsessive-compulsive disorder: a systematic review and meta-analysis.
BMC Psychiatry. 14:317.
26. Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ,
et al. (2013): Cognitive-behavioral therapy vs risperidone for augmenting
serotonin reuptake inhibitors in obsessive-compulsive disorder: a
randomized clinical trial. JAMA Psychiatry. 70:1190-1199.
27. Serata D, Kotzalidis GD, Rapinesi C, Janiri D, Di Pietro S, Callovini G,
et al. (2015): Are 5-HT3 antagonists effective in obsessive-compulsive
disorder? A systematic review of literature. Human Psychopharmacology.
30:70-84.
28. Fontenelle LF, Coutinho ESF, Lins-Martins NM, Fitzgerald PB,
Fujiwara H, Yücel M (2015): Electroconvulsive therapy for obsessive-
compulsive disorder: a systematic review. The Journal of Clinical
Psychiatry. 76:949-957.
29. Trevizol AP, Shiozawa P, Cook IA, Sato IA, Kaku CB, Guimaraes FB,
et al. (2016): Transcranial Magnetic Stimulation for Obsessive-Compulsive
Disorder: An Updated Systematic Review and Meta-analysis. The Journal
of ECT.
30. Leiphart JW, Valone FH (2010): Stereotactic lesions for the treatment of
psychiatric disorders. Journal of Neurosurgery. 113:1204-1211.
31. Pepper J, Hariz M, Zrinzo L (2015): Deep brain stimulation versus anterior
capsulotomy for obsessive-compulsive disorder: a review of the literature.
Journal of Neurosurgery. 122:1028-1037.
32. Alonso P, Cuadras D, Gabriels L, Denys D, Goodman W, Greenberg BD,
et al. (2015): Deep Brain Stimulation for Obsessive-Compulsive Disorder:
A Meta-Analysis of Treatment Outcome and Predictors of Response. PloS
One. 10:e0133591.
33. Skapinakis P, Caldwell D, Hollingworth W, Bryden P, Fineberg N,
Salkovskis P, et al. (2016): A systematic review of the clinical effectiveness
and cost-effectiveness of pharmacological and psychological interventions
for the management of obsessive-compulsive disorder in children/
adolescents and adults. Health Technology Assessment (Winchester,
England). 20:1-392.
34. Simpson HB, Foa EB, Liebowitz MR, Ledley DR, Huppert JD, Cahill S,
et al. (2008): A randomized, controlled trial of cognitive-behavioral therapy
for augmenting pharmacotherapy in obsessive-compulsive disorder. The
American Journal of Psychiatry. 165:621-630.
35. Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ,
et al. (2013): Cognitive-behavioral therapy vs risperidone for augmenting
serotonin reuptake inhibitors in obsessive-compulsive disorder: a
randomized clinical trial. JAMA Psychiatry. 70:1190-1199.
36. Andersson E, Enander J, Andren P, Hedman E, Ljotsson B, Hursti T, et
al. (2012): Internet-based cognitive behaviour therapy for obsessive-
compulsive disorder: a randomized controlled trial. Psychological
Medicine. 42:2193-2203.
37. Tumur I, Kaltenthaler E, Ferriter M, Beverley C, Parry G (2007):
Computerised cognitive behaviour therapy for obsessive-compulsive
disorder: a systematic review. Psychotherapy and Psychosomatics.
76:196-202.
38. Amerio A, Odone A, Marchesi C, Ghaemi SN (2014): Treatment of comorbid
bipolar disorder and obsessive-compulsive disorder: a systematic review.
Journal of Affective Disorders. 166:258-263.
39. Marchesi C, Ossola P, Amerio A, Daniel BD, Tonna M, De Panfilis C
(2016): Clinical management of perinatal anxiety disorders: A systematic
review. J Affect Disord. 190:543-550.
40. Ivarsson T, Skarphedinsson G, Kornor H, Axelsdottir B, Biedilae S,
Heyman I, et al. (2015): The place of and evidence for serotonin reuptake
inhibitors (SRIs) for obsessive compulsive disorder (OCD) in children and
adolescents: Views based on a systematic review and meta-analysis.
Psychiatry Research. 227:93-103.
41. Bloch MH, Landeros-Weisenberger A, Rosario MC, Pittenger C,
Leckman JF (2008): Meta-analysis of the symptom structure of obsessive-
compulsive disorder. The American Journal of Psychiatry. 165:1532-1542.
42. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J,
Weiller E, et al. (1998): The Mini-International Neuropsychiatric Interview
(M.I.N.I.): the development and validation of a structured diagnostic
psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 59 Suppl
20:22-33;quiz 34-57.
43. First MB, Williams JBW, Karg RS, Spitzer RL (2015): Structured
Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV).
Arlington, VA, American Psychiatric Association.
44. Rosario-Campos MC, Miguel EC, Quatrano S, Chacon P, Ferrao Y,
Findley D, et al. (2006): The Dimensional Yale-Brown Obsessive-
S89
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]

Reddy, et al.: CPGs for OCD

Compulsive Scale (DY-BOCS): an instrument for assessing obsessive-
compulsive symptom dimensions. Molecular Psychiatry. 11:495-504.
45. Eisen JL, Phillips KA, Baer L, Beer DA, Atala KD, Rasmussen SA (1998):
The Brown Assessment of Beliefs Scale: reliability and validity. The
American Journal of Psychiatry. 155:102-108.
46. Neziroglu F, McKay D, Yaryura-Tobias JA, Stevens KP, Todaro J (1999):
The Overvalued Ideas Scale: development, reliability and validity in
obsessive-compulsive disorder. Behaviour Research and Therapy.
37:881-902.
47. Obsessive Compulsive Cognitions Working G (2005): Psychometric
validation of the obsessive belief questionnaire and interpretation of
intrusions inventory--Part 2: Factor analyses and testing of a brief version.
Behaviour Research and Therapy. 43:1527-1542.
48. Calvocoressi L, Lewis B, Harris M, Trufan SJ, Goodman WK,
McDougle CJ, et al. (1995): Family accommodation in obsessive-
compulsive disorder. The American Journal of Psychiatry. 152:441-443.
49. Hazari N, Narayanaswamy JC, Arumugham SS (2016): Predictors of
response to serotonin reuptake inhibitors in obsessive-compulsive
disorder. Expert Review of Neurotherapeutics. 16:1175-1191.

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CLINICAL PRACTICE GUIDELINES
Clinical Practice Guidelines for Management of Schizophrenia
Sandeep Grover, Subho Chakrabarti, Parmanand Kulhara, Ajit Avasthi
Department of Psychiatry, PGIMER, Chandigarh
Participants of expert group on CPG for Schizophrenia
B.N. Gangadhar, P.K. Dalal, Lalit Batra, Kishore Gujar,
O.P Singh, Bharat Singh, Abhay Matkar, Devendra
Vijayvargiya, R.K. Solanki, Adarsh Tripathi
INTRODUCTION
Schizophrenia is a serious mental disorder with prevalence
rates of 2-3 per 1000 reported from India. The impact of
schizophrenia on patients, their families and the wider
society are no different from what has been observed in
the rest of the world. However, resource constraints,
poverty, lack of education and inadequate access to health
care facilities for patients make the problem of providing
care particularly daunting in India. In 2005, the Indian
Psychiatric Society came up with treatment guidelines for
schizophrenia tailored to meet the requirements of our
patients in the context of prevailing existing resources.
There have been several developments in the management
of schizophrenia since then. These new set of guidelines
attempt to update the previous guidelines by emphasizing
what is new in the field. These guidelines ought to be read
in conjunction with the earlier version of the treatment
guidelines on schizophrenia as developed and published by
the Indian Psychiatric Society in the year 2005.
SCOPE OF THIS DOCUMENT
The major emphasis of the current guidelines is on areas in
the management of schizophrenia, which have witnessed
significant developments since the publication of the
Address for correspondence:
Dr. Ajit Avasthi, Department of Psychiatry,
Postgraduate Institute of Medical Education and Research,
Chandigarh ‑ 160 012, India.
E-mail: drajitavasthi@yahoo.co.in
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DOI:
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© 2017 Indian Journal of Psychiatry | Published by Wolters Kluwer ‑ Medknow
previous guidelines. These guidelines are not particularly
applicable to any specific treatment setting and may need
minor modifications to suit the needs of patients in a
specific setting. The recommendations are primarily meant
for adult patients. The needs of children or the elderly with
schizophrenia may be different. Finally, it is expected that
recommendations made will have to be tailored to suit the
needs of individual patients.
Assessment and evaluation (table-1)
A comprehensive assessment of the patient and his/her
caregivers needs to be carried out. The cornerstone of this
assessment is a detailed history and physical and mental state
examinations. Efforts should be made to obtain information
from all sources, especially the family. Wherever possible,
diagnosis of schizophrenia be preferably made according
to current diagnostic criteria, as such a diagnosis is more
reliable. A reliable diagnosis facilitates communication
among clinicians, and allows for better applicability
of evidence-based recommendations. Many clinical
conditions that may mimic schizophrenia include mood
disorders, substance-induced psychoses and psychoses
secondary to physical illnesses. These should be ruled out
as far as possible by history, examination and additional
investigations. In some instances a definitive diagnosis may
need time. Further, because of the enormous psychosocial
consequences a diagnosis of schizophrenia needs to be
made with great caution and sensitivity. In doubtful cases,
a medication-free observation period can be considered.
However, consideration of medication free period need to
be balanced against the risks of delaying treatment or the
potential for harm to self and others in acutely ill patients.
It is important to remember that diagnosis is not a one-time
affair, but a continuous process. Accordingly, based on the
subsequent information from patients and caregivers, and
on repeated clinical evaluations the diagnosis may need re-
evaluation.
This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
How to cite this article: Grover S, Chakrabarti S, Kulhara
P, Avasthi A. Clinical Practice Guidelines for Management of
Schizophrenia. Indian J Psychiatry 2017;59:19-33.
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Grover, et al.: CPG for Schizophrenia
The assessment should cover all other areas such as
symptom dimensions, symptom-severity, comorbid
psychiatric and medical conditions, particularly comorbid
substance abuse, the risk of harm to self or others, level of
functioning and the socio-cultural milieu of the patient. A
high index of suspicion along with thorough assessment can
help in detecting most patients with comorbid substance
abuse/dependence. Wherever, facilities are available, urine
or blood screens (with prior consent) can be used to confirm
the presence of comorbid substance abuse/dependence. A
thorough physical examination need to be done to rule out
presence of any physical illness and also to rule out psychoses
secondary to physical illnesses. This may be supplemented
by the judicious use of investigations. Wherever possible,
unstructured assessments need to be supplemented by
ratings on appropriate standardized rating scales. Other
options such as detailed cognitive testing can be done if
required and feasible. The use of neuroimaging may be
indicated in those with first-episode psychosis, neurological
signs, non-response to treatment and elderly patients.
Assessments of caregivers may focus on areas such as their
knowledge and understanding of the illness, their attitudes
and beliefs regarding treatment, the impact of the illness on
them and their personal and social resources.
It is important to remember that assessment is an ongoing
process. As the treatment progresses other areas such as response
to treatment, side effects, treatment adherence, the impact of
patient’s immediate environment, disability assessments, other
health-care needs, ease of access and relationship with the
treatment team may need to be assessed separately.
Formulating a treatment plan (figure 1)
Formulation of treatment plan involves deciding about
treatment setting, treatments to be used and areas to be
addressed. Patients, caregivers and staff involved in care
may be consulted while preparing the treatment plan.
Treatment plans be needs-based, practical, feasible and
flexible. These should be continuously re-evaluated and
modified as required.
Choice of treatment settings
The basic principle while choosing a treatment-setting
is to provide care in the least restrictive setting, which
nevertheless meets the needs of patients and caregivers. The
commonest treatment settings would be either outpatient
clinics or inpatient wards. In some instances resources for
long-term inpatient care, or community or residential care
may be available. The bulk of the patients would probably
receive treatment in outpatient settings. Given their severe
shortage, inpatient beds are likely to be scarce. Common
indications for inpatient care during acute episodes are
shown in table-2. Whenever possible patient admitted to
the inpatient setting should have accompanying family
caregivers. In case inpatient care facilities are not available,
S20
Table 1: Components of assessment and evaluation
Basic assessments
• Comprehensive assessment of both patients and caregivers
• Complete history with information from all possible sources
• Physical examination‑ record data such as blood pressure, weight and
wherever indicated body mass index and waist circumference
• Mental state examination
• Establish diagnosis according to current diagnostic criteria
• Differential diagnosis by ruling out secondary psychoses
• Areas to be evaluated: symptom‑severity, symptom‑dimensions (reality
distortion, disorganization, negative, depressive and cognitive
symptoms), comorbid physical, psychiatric and substance use
conditions, risk of harm to self and others, level of functioning and
socio‑cultural milieu of the patient
• Basic investigations: haemogram, blood sugars and lipid levels, liver
functions, renal functions, electrocardiogram (focus on QTc)
• Assessments of caregivers: knowledge and understanding of the illness,
attitudes and beliefs regarding treatment, impact of the illness on them,
personal and social resources
• Ongoing assessments: response to treatment, side effects, treatment
adherence, the impact of patient’s immediate environment, disability
assessments, other health‑care needs, ease of access and relationship
with the treatment team
Additional/Optional assessments
• Use of standardized rating scales to rate all aspects of the illness
• Psychological testing for cognitive functions
• Neuroimaging especially in those with first‑episode psychosis,
neurological signs, non‑response to treatment and elderly patients
Table 2: Some indications for inpatient care during
acute episodes
• Presence of suicidal behaviour which puts the life of the patient at risk
• Presence of severe agitation or violence which puts the life of others at risk
• Refusal to eat which puts the life of patient at risk
• Severe malnutrition
• Patient unable to care for self to the extent that she/he requires constant
supervision or support
• Catatonia
• Presence of general medical or comorbid psychiatric conditions which
make management unsafe and ineffective in the outpatient setting
than the patient and/or family need to be informed about
such a need and admission in nearest available inpatient
facility may be facilitated.
Options for management for schizophrenia
Treatment options for management of schizophrenia
can be broadly classified as antipsychotic medications,
electroconvulsive therapy (ECT), adjunctive medications
and psychosocial interventions (table-3).
Pharmacological treatment
Choice of antipsychotic medication
The essential choice is between using an antipsychotic
belonging to the class of typical antipsychotics (FGA- first-
generation antipsychotic) or from the atypical group (SGA-
second-generation antipsychotic). Since the publication of
the previous guideline there is somewhat greater clarity on
this matter. The bulk of the evidence including large-scale
real-world studies indicates that there is very little difference
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Patient with Psychotic features

Consider differential diagnoses like

• Organic Mental Conditions
• Acute and transient psychotic disorder
• Persistent Delusional disorder
• Schizoaffective disorder
• Severe depression with psychotic symptoms
• Mania with psychotic symptoms
• Drug induced psychosis

Establish the diagnosis of schizophrenia

Assessment
• Severity of illness
• Risk of harm to self and others
• Comorbid substance use/dependence
• Level of functioning
• Detailed Physical examination
• Record- blood pressure, weight and wherever indicated body mass index and waist
circumference
• Mental Status Examination
• Investigations- haemogram, liver function test, renal function test, fasting blood glucose
level, electrocardiogram (focus on QTc)
• Treatment history- response to previous medication trials, compliance, side effects, etc.
• Patient’s and caregivers beliefs about the cause of illness and beliefs about the treatment
• Assessment for social support, stigma, coping
• Assessment of caregiver burden, coping and distress

• Decide about treatment setting- consider inpatient care in case of suicidality, severe agitation
and violence, malnutrition, catatonia, patient unable to care for self to the extent that she/he
requires constant supervision or support, comorbid general medical conditions making
management difficult at the outpatient setting
• Liaison with other specialists depending on the need of the patient

Pharmacological Management Electroconvulsive therapy Non-Pharmacological

• Choose an antipsychotic based on past • Catatonia, affective Management
treatment response, past history of side symptoms, rapid control • Psychoeducation
effects, cost, comorbidity, Patient/family of symptoms, suicidality, • Psychosocial
preference, preferred route of past response to ECT, intervention
administration, availability, current metabolic augmentation etc.
profile, past history of compliance,
treatment resistance

Figure-1: Initial evaluation and management plan for schizophrenia

Table 3: Options for management for schizophrenia in terms of efficacy, adherence and other subjective aspects
Antipsychotic medications between the FGA and the SGA group, or between individual
First‑generation antipsychotic medications (Oral/parenteral/depot or long antipsychotics belonging to either group. The only exception
acting‑ preparations) to this trend is clozapine, which appears to be more
Second‑generation antipsychotic medications (Oral/parenteral/depot or long efficacious than any other antipsychotic in patients with
acting‑ preparations)
Somatic treatments
treatment resistance. It follows from this that the choice of
Electroconvulsive therapy (ECT) the antipsychotic will depend on factors other than efficacy.
Adjunctive medications Some of these factors are included in table-4.
Anticholinergics, antidepressants, benzodiazepines, hypnotic‑sedatives,
anticonvulsants, lithium carbonate Dose
Psychosocial interventions
Family intervention, cognitive behavioural therapy, social skills training,
The recommended dose of various oral antipsychotics
cognitive remediation, individual therapy, group therapy, vocational available in India is shown in table-5. In general patients
rehabilitation, early‑intervention programmes, case management, with first-episode psychosis respond to lower doses. The use
community mental‑health teams, crisis resolution teams of high or very high doses (mega doses) of antipsychotics,
Other measures if required, may be used with caution in exceptional
Lifestyle and dietary modifications
circumstances. It is noted that Indian patients require lower

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doses of antipsychotic drugs compared to patients from the Table 4: Factors that influence selection of
West. Although this is suggested by clinical experience and antipsychotics
pharmacokinetic studies of Asian patients, there is little • Past treatment response
evidence for, or against this supposition from clinical trials. • Cost of treatment, affordability
• Psychiatric comorbidity
Route of administration • Medical comorbidity
• Side effects
Acutely agitated patients often require parenteral • Patient or family preference
administration of antipsychotics to rapidly control the • Preferred route of administration
behavioural disturbance. Liquid or mouth-dissolving • Concomitant medications
formulations are often helpful in non-compliant patients. • Non‑adherence
Depot preparations are generally not used in acutely • Treatment resistance
agitated patients except zuclopenthixol acetate, which has
a half-life of about 20 hours. In general, it is recommended Table 5: Recommended therapeutic dose ranges for
that one drug is to be used by one route in order to minimise various antipsychotics
drug interactions and simplify clinical observations.
Usual daily dose Maximum
(in mg/day) daily dose
Depot preparations (table-6) are often helpful in ensuring First Generation Antipsychotics (FGAs)
medication-compliance and may be used in situations Chlorpromazine 300‑800 800
where compliance is a problem. Depot injectables may Haloperidol 5‑20 20
also be used if patients/relatives indicate a preference for Penfluridol 20‑60 mg/week 250 mg/week
this kind of treatment. Test doses are administered at the Perphenazine 12‑64 64
Pimozide 4‑10 10
start of treatment. When used, depot preparations need to
Thioridazine 300‑800 800
be prescribed within the standard recommended dosage Trifluoperazine 15‑30 30
and interval range to achieve optimum effectiveness in Zuclopenthixol 10‑50 50
preventing relapse. Second Generation Antipsychotics (SGAs)
Amisulpride 50‑800 1200
Aripiprazole 10‑30 30
Adequate antipsychotic trial
Asenapine 10‑20 20
The minimum recommended duration of treatment to Blonanserin 2‑8 24
consider it to be an effective trial for all antipsychotics is use Clozapine 150‑600 900
of medication in the highest tolerable dose for 6-8 weeks, Iloperidone 12‑24 24
with the exception of clozapine, where the minimum period Olanzapine 10‑30 30
Paliperidone 3‑12 12
of treatment is at least 3-6 months.
Quetiapine 300‑800 800
Risperidone 2‑8 16
Response Ziprasidone 80‑200 200
Antipsychotics are known to produce a significant remission Zotepine 75‑300 300
of positive symptoms. This could thus be a reasonable goal
of treatment during the acute phase. Antipsychotics are less
effective in management of negative symptoms, therefore a
Table 6: Antipsychotic depot preparations available in
mild to moderate reduction in negative symptoms is often
India
acceptable. Response indicators for other aspects of the
Name of antipsychotic Usual 2‑4 weekly dose in mg
illness (e.g. cognitive symptoms) are not clear. Patients on
Zuclopenthixol decanoate 200
antipsychotics need to be monitored regularly to ascertain
Paliperidone palmitate 234 initially followed by 117 monthly
the level of response and the emergence of side effects. Fluphenazine decanoate 12.5‑50
Haloperidol decanoate 50
Non-response (Figure-2) Risperidone depot 25‑50
In case a patient fails to respond to an antipsychotic (RisperidalConsta)
medication, poor compliance or non-compliance need Olanzapine pamoate 210‑405
to be evaluated prior to switching the medication to
another antipsychotic. If a patient is found to have poor with good compliance, a change in antipsychotic may be
compliance or non-compliance to medications, all efforts considered. Clozapine need to be considered after failure of
are to be made to understand the causes responsible for sequential trials of 2 antipsychotics (at least one of which is
lack of compliance and appropriate steps need to be a SGA). Clozapine may also be considered earlier in patients
taken to handle the problem. However, if a patient fails to who are violent, at risk for suicide, not responding to their
respond to an adequate trial of an antipsychotic medication current medication and those experiencing intolerable side
(i.e., adequate dose for at least 6-8 weeks duration) taken effects with two different classes of antipsychotics.

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Patient given an adequate Adequate Response

antipsychotic trial (adequate dose for • Continue with the same
atleast 6 weeks duration) dose of antipsychotic
medication and keep on
monitoring the side effects

Non-response to treatment

Evaluation
• Re-evaluate the diagnosis
• Medication compliance

True Non-response Pseudo Non-response due to poor compliance

• Change the antipsychotic • Evaluate the causes, address the same and
medication ensure compliance
• In case of poor compliance due to intolerable
side effects –consider change of antipsychotic
(oral/depot)

Failure of 2 adequate trials of Adequate Response

antipsychotic, one of which is SGA • Continue with the same dose of
• Consider clozapine antipsychotic medication and keep
on monitoring the side effects

Inadequate Response to clozapine

• Consider combining clozapine with ECT
or another antipsychotic medication
• More intensive psychosocial intervention

Figure 2: Evaluation of patient with non-response to antipsychotic medications

Combination of antipsychotics is not recommended. It is better to start these drugs when

There is limited evidence for the efficacy of combination
of antipsychotics. In the initial phase, a clinician may
be compelled to use a combination of antipsychotics to
manage agitation, but caution need to be exercised while
doing so. These should be used on SOS basis and for
shortest possible time. Combinations of antipsychotics for
prolonged periods may be avoided, except in patients not
responding to clozapine.
ADJUNCTIVE MEDICATIONS
Although antipsychotic agents are the mainstay of
treatment of schizophrenia, management may involve
use of adjunctive treatments like with antidepressants,
mood stabilizers or benzodiazepines. However, these can
be used with proper rationale and for shortest possible
duration. At every assessment a proper evaluation need
to be done for the continuation of the same. Lithium and
other mood stabilizers can be prescribed in agitated,
overactive patients or those with affective symptoms
responding poorly to their current drug. Benzodiazepines
can be useful in managing agitation and sleep disturbance.
Antidepressants may be of use in post-psychotic depression
and may be avoided when the patient has florid psychotic
symptoms. In general prophylactic use of anticholinergics
the patient actually develops extrapyramidal side effects.
Whenever anticholinergic agents are required, use may be
limited to lowest possible doses and for shortest possible
time.
ELECTROCONVULSIVE THERAPY (ECT)
As in many other developing countries ECT is used quite
frequently in schizophrenia in India. The evidence for
efficacy of ECT in the acute phase of schizophrenia is
somewhat controversial. There is evidence for augmentation
and acceleration of response. ECT is used in conjunction
with antipsychotics in the acute phase, but the extent of the
benefit of adding ECT to antipsychotics is unclear and the
positive effects seem to last only for the first few weeks of
treatment. However, there may be some merit in adding ECT
to the treatment regimen in patients who respond poorly to
antipsychotics. The more unequivocal indications for ECT
in combination with antipsychotics are included in table-7.
ECT is not useful in chronic schizophrenia and there is not
enough evidence to recommend its use in the longer term
except in exceptional circumstances. Finally, whenever ECT
is used adequate information and support for patients and
caregivers, informed consent, proper administration and
careful monitoring of response and side effects be done.

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PSYCHOEDUCATION FOR PATIENTS AND OR
FAMILY (TABLE-8)
Psychoeducation may be considered both for the patient and
family members. The aim is to educate the patient and family
about the illness. Simple and brief explanations about the
nature of the patient’s illness, treatments, likely side effects,
likely length of treatment etc. can be offered. Relatives also
need to be given time to confront the painful fact of the illness,
and what it entails for the patient and the family as a whole.
It is important that professionals are careful and considerate,
but clear and thorough in their use of clinical language and
in the explanations they provide. No blame is to be attached
to the family. Treatment adherence will be another main
objective at this stage. Prior to every session, feedback of the
previous sessions may be taken and psychoeducation is to be
tailored to the needs of the patient and the caregivers.
PSYCHOSOCIAL INTERVENTIONS
Psychosocial interventions are acknowledged to be an
integral part of management of schizophrenia. Different
psychosocial interventions including family treatments,
cognitive behavioural therapy, social skills training, cognitive
remediation, individual supportive therapy, group therapy,
vocational rehabilitation, case management, use of community
Table 7: Possible indications of use of ECT in patients of
schizophrenia
• Catatonic symptoms
• Affective symptoms
• Need for rapid control of symptoms
• Presence of suicidal behaviour which puts the life of the patient at risk
• Presence of severe agitation or violence which puts the life of others at risk
• Refusal to eat which puts the life of patient at risk
• History of good response in the past
• Patients not responding to adequate trial of an antipsychotic medication
• Augmentation of partial response to antipsychotic medication
• Clozapine resistant schizophrenia
• Not able to tolerate antipsychotic medications
Table 8: Basic components of Psychoeducation
• Assessing the knowledge of the patient and caregivers about aetiology,
treatment and prognosis
• Introducing the diagnosis of schizophrenia into discussion
• Discussing about various symptom dimensions
• Providing information about aetiology
• Providing information about treatment in terms of available options, their
efficacy/effectiveness, side effects, duration of use
• Discussing about importance of medication and treatment compliance
• Providing information about possible course and long term outcome
• Discussing about problems of substance abuse, marriage and other issues
• Discussing about Communication patterns, problem solving, disability
benefits
• Discussing about relapse and how to identify the early signs of relapse
• Dealing with day today stress
• Improving insight into illness
• Handling expressed emotions and improving communication
• Enhancing adaptive coping to deal with persistent/residual symptoms
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mental-health teams and of crisis resolution teams have been
proven to be useful in the management of schizophrenia.
The usefulness and delivery of psychosocial treatments has
probably not attracted the research attention it deserves in the
Indian context. Nevertheless, there is ample Indian evidence
and experience with family treatments, rehabilitation and
other modalities such as community programmes, yoga and
cognitive remediation. Based on these data, psychosocial
interventions, from the simple to the complex, can be
recommended for patients with schizophrenia and their
families. An approach which prioritizes the needs of patients
and their families could be followed.
FAMILY INTERVENTIONS
There has been a long tradition in India of involving
families in the care of their members with mental illness.
There are several studies documenting the delivery of
family interventions. Several formats of predominantly
psychoeducational treatments such as informal or
unstructured programmes, structured treatments, group-
based interventions, and integrated psychosocial treatments
have been tried. From the number of controlled trials it
appears that a wide range of interventions and treatment-
delivery, from the simple to the complex, may be useful
in the Indian context. The basic emphasis need to be on
continued contact and medication adherence while offering
emotional and practical support. A needs-based approach,
in which interventions are tailored to the background
and needs of the families, is more likely to enhance their
acceptability and positively influence the readiness of
families to participate in such interventions.
ADVISE FOR LIFE STYLE AND DIETARY
MODIFICATIONS
All the patients are to be advised for a change in the life
style and diet to reduce the risk of metabolic side effects
and cardiovascular morbidity and mortality. These include
physical exercises, dietary modifications and abstinence
from smoking etc.
REHABILITATION
Similar to family treatments, rehabilitation programmes
need to be be culturally moulded and adapted to the
needs of patients and their families. However, unlike family
interventions, resources for more elaborate rehabilitation
strategies may not be available in every centre. Nevertheless,
relatively simple and inexpensive strategies can form a part
of the overall psychosocial intervention package.
INDIVIDUAL SUPPORTIVE THERAPY
A supportive empathic relationship between patients and
professionals, in which good listening promotes a lasting
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therapeutic alliance is an essential part of good practice.
Additional elements could include support and advice,
encouraging continued engagement, treatment-adherence
and healthy lifestyles. Efforts to minimize stress may also
be beneficial. Individual support along with medication is
the most commonly practiced treatment in schizophrenia.
Patients and families consistently rank individual support as
among the most highly valued services offered to patients
with schizophrenia.
OTHER PSYCHOSOCIAL INTERVENTIONS
Other interventions that hold promise are home-based
care, support groups for caregivers, community-based
interventions, cognitive training or remediation, and yoga.
More research on the efficacy of these strategies and their
wider implementation is needed.
Basic components of any psychosocial intervention are
depicted in table-9. For more specific recommendations
other sources may be consulted.
TREATMENT ADHERENCE
Adherence is defined as “the extent to which the
patients’ behaviour, in terms of regular clinic visit, taking
medications, following diets, executing lifestyle changes,
coincide with the clinical prescription”. Non-adherence
in this context thus denotes failure to enter a treatment
programme, premature termination of treatment, or
incomplete implementation of instructions, including
those that pertain to medication administration. Evidence
suggests that about half of the patients with schizophrenia
do not comply with the treatment recommendations,
about one-third miss their appointments with the
clinicians and 20-60% of patients drop out from treatment.
Common factors associated with poor medication non-
compliance are shown in table-10. Factors consistently
linked to non-adherence include poor insight, negative
attitude or subjective response to medication, comorbid
substance abuse, and poor therapeutic alliance. Clinicians
need to make efforts to reduce the rates of medication
compliance and treatment non-adherence. It is important
for the clinicians to understand that besides the
contextual or situation factors, patient related factors
and illness related factors, certain clinician related
factors are responsible for poor medication compliance
and higher dropout rates. Some of the common clinician
related factors which may be relevant in Indian context
include poor communication between the clinician and
the patient/caregiver, poor therapeutic alliance and non-
collaborative decision-making. Hence, clinicians need to
focus on better communication and improve therapeutic
alliance with patient and the family to improve overall
outcome. Whenever clinicians encounter poor medication
Indian J Psychiatry 59 (Supplement 1), January 2017
Table 9: Recommendations about psychosocial
interventions
• Assessment of psychosocial factors involving the patient and the family is
an integral part of psychosocial interventions.
• There is a wide range of interventions that have proved useful in Indian
settings
• Choice of the intervention will be shaped by the needs of patients and
their families as well as the resources available.
• Basic components of any intervention include: promoting a therapeutic
alliance with the patient and the family, encouraging ongoing
engagement, information about various aspects of the illness, focusing on
treatment‑adherence and healthy lifestyles, and offering emotional and
practical support.
Table 10: Factors associated with poor medication
compliance
Demographic risk factors
• Younger age, male gender, unemployment, lower socioeconomic status
Patient related factors
• Knowledge about illness and treatment, perceived need for
treatment (insight), motivation, beliefs about treatment risks and benefits,
past experiences/“transference”, past history of adherence, self‑stigma
Social risk factors
• Living independently, poor social support, poor financial support
Clinical risk factors
• Poorer premorbid functioning, earlier age of onset, prior history of
non‑adherence
Symptom‑related risk factors
• Lack of insight, paranoia, grandiose delusions, conceptual
disorganization, impaired cognition, substance abuse, comorbidities,
depression, refractoriness, spontaneous remissions
Treatment‑related risk factors
• Medication side effects, poor treatment alliance, complex dosing,
negative experience of medication, route of administration, length of
treatment, cost of treatment, number of medications
Service‑related risk factors
• High cost of medication, poor accessibility of treatment services
Family/caregivers‑related risk factors
• Lack of supervision, negative attitudes towards treatment, lack of
knowledge about medicines, nature of relationship with patient,
perceived need for treatment, beliefs about benefits and risks with
continued treatment, involvement in treatment, stigma, financial
constraints, support from other sources
Clinician/provider related factors
• Therapeutic alliance, frequency and nature of contact with clinicians,
expected duration of treatment, duration of past treatment, accessibility
to clinicians and services, reimbursement, psychoeducation and
psychosocial treatment, complexity of administration
or treatment compliance, all efforts need to be made
to understand the reasons behind the same. Proper
evaluation of non-adherence need to cover assessment
of familial, social, biological and pharmacological
perspectives. Patients/caregivers concerns need to be
addressed by proper psychoeducation and modification of
pharmacological treatment. Medication compliance can be
improved by using depot preparations and use of mouth
dissolving formulations under supervision. Evidence
also suggests beneficial effects of cognitive-behavioural
approaches and motivational interviewing.
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PHASES OF ILLNESS/TREATMENT
Management of schizophrenia can be broadly divided into
three phases, i.e., acute phase, continuation treatment or
stabilization phase, maintenance or stable phase. Some
patients may present very early in a prodromal phase and
appropriate strategies for detection and management for
this phase might be required.
Prodromal stage
It is now well known that onset of frank psychosis is often
preceded by psychological and behavioral abnormalities
involving cognition, emotion, perception, communication,
motivation and sleep. These symptoms may precede the
psychosis by weeks to years. Various diagnostic systems
categorise the symptoms as: basic symptoms, attenuated
positive symptoms, brief limited intermittent psychotic
symptoms, features of schizotypal personality disorder,
genetic risk paired with functional deterioration, as well
as general symptoms that are not specific to psychosis.
Evidence also suggests that many patients with prodrome,
especially the high risk group have higher chance of
conversion to frank schizophrenia. Conversion rates have
been reported to range from 25-40%. Further, prodrome
itself may have negative impact on the social, emotional
and cognitive development. Therefore, now more and
more emphasis is laid on early detection and intervention.
Factors which have been shown to predict conversion to
psychosis include presence of genetic risk with recent
deterioration in functioning, higher degree of unusual
thought content, suspiciousness/paranoia, presence of
social impairment, longer duration of symptoms, high
levels of depression, reduced attention and history of
substance abuse. In terms of management of prodrome
it is suggested that treatment ought to be based on the
needs of the patient. There is some evidence to suggest
that use of antipsychotics in prodromal phase can delay the
conversion to psychosis and antidepressants may be useful
in symptomatic improvement in a sub-group of patients.
However, at present evidence for use of antipsychotics in
prodromal phase is not convincing to recommend its use in
all patients. There is also preliminary evidence to suggest
the beneficial effect of certain agents like omega-3 fatty
acids. In contrast, evidence suggest that psychological
interventions like cognitive behaviour therapy, cognitive
therapy, psychosocial stress management, etc can improve
functioning and symptomatology during the prodromal
phase, although the active components of these treatments
are not well known. Accordingly, whenever a patient
presents with symptoms suggestive of prodromal phase of
schizophrenia, initial management is done in the form of
psychosocial intervention. Use of pharmacotherapy need to
be weighed against the side effects of antipsychotics and
sensitization of dopamine receptors in brain, which can
possibly lead to supersensitivity psychosis or rapid-onset
psychosis following stoppage of antipsychotic medication.
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MANAGEMENT IN THE ACUTE PHASE OF
TREATMENT
Most patients in this stage are likely to exhibit florid
psychotic symptoms such as delusions or hallucinations,
disorganized thinking and behavioural disturbances. Their
functioning may be severely impaired and they can be at
risk of harming themselves or others. Additionally both the
patient and the family might have considerable difficulty in
coming to terms with the onset of acute symptoms. The
various aspects of management in the acute phase are
included in table-11.
MANAGEMENT IN THE CONTINUATION
TREATMENT PHASE
This phase begins once the acute symptoms reduce in
severity or remit and conventionally lasts for about 6-12
months. Different components of this phase are shown in
table-12. Consolidation of remission, continued reduction
in symptoms and prevention of early relapses are the usual
treatment objectives during this phase. Reduction of stress
on the patient and the family by continuing engagement
Table 11: Management in the acute phase
Comprehensive assessment (psychiatric/medical/psychosocial)
Deciding on goals of treatment
Patients
Eliminate/reduce symptoms of schizophrenia and improve the level of
functioning
Promote safety, reduce risk of harm, reduce stress
Caregivers
Minimise caregiver distress
Offer help to enable them to cope with the illness in their relative
Both
Develop a therapeutic alliance and provide opportunities for patients and
caregivers to actively engage in treatment
Offer basic information and support tailored to needs of patients and
caregivers
Choice of treatment setting
Antipsychotic treatment
Choice of drug
Dose
Route of administration
Duration of treatment
Determining response or non‑response
Combining antipsychotics
Use of adjunctive medications when indicated
Use of ECT when indicated
Psychosocial interventions‑ relatively basic and mainly for the purpose
of fulfilling the goals of treatment listed above
Planning for further treatment
Table 12: Management in the continuation treatment
phase
Determining goals
Further assessment
Antipsychotic treatment
Psychosocial interventions
Monitoring for response, side effects and treatment adherence
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and support and enhancing their adaptation to life after
discharge from the hospital, are other important goals of
management. Management includes continuing medication
treatment, monitoring of response and side effects and
furthering psychosocial interventions. Medications need
to continue preferably at the same dose for the next 6-12
months. The continued goals of psychosocial treatment are
to maintain treatment engagement and adherence, offer
support for patients and their families and help prepare
the patient for life in the community. More elaborate
psychosocial interventions may be tried at this stage.
Finally, regular monitoring of response, side effects and
treatment-adherence needs to continue.
MANAGEMENT IN THE MAINTENANCE OR
STABLE PHASE
During this phase of illness, symptoms are stable and
usually less severe than in the acute stage. Negative
symptoms may predominate and deficits in social and
occupational functioning become more apparent.
Maintaining or improving level of functioning, prevention
of recurrences and promoting psychological/personal
recovery are the major aims of treatment during this
phase of management. Different components of this phase
are shown in table-13.
During this phase, follow-ups can be scheduled once every
2-3 months and more frequently in times of crises, or if
desired by the family. During this phase of management,
regular feedback need to be obtained from the family.
Any new issues that arise are discussed and some of the
previous issues may need reemphasis. Management in
the stable phase involves carrying forward the gains
achieved. The management plan should be relooked for
any need for change. It also involves determining the
goals, continuing further assessment, continuing with
antipsychotic medications and monitoring of side effects
and furthering the psychosocial interventions. In addition
the management need to focus on rehabilitation, enhancing
personal recovery.
Goals of treatment: The goals of treatment during this
phase are to maintain or improve functioning, improve
quality of life and facilitate personal recovery. Psychotic
exacerbations need to be effectively treated. Adverse effects
are to be noted and managed.
Table 13: Management in the maintenence phase
• Determining goals
• Re‑evaluating/modifying the treatment plan
• Assessments and monitoring
• Antipsychotic treatment
• Psychosocial interventions
• Monitoring for response, side effects and treatment adherence
• Early intervention for relapses
Indian J Psychiatry 59 (Supplement 1), January 2017
Re-evaluating/modifying the treatment plan: As time elapses
the nature of the illness, problems faced by the relatives,
needs of the patient and the family and previously determined
targets are all expected to change. Regular contact, awareness
and monitoring are needed to detect these changes. Ongoing
assessment is thus essential. It allows those modifications to be
made in the treatment plan, which are required to accommodate
any new problems or demands that may have arisen.
Assessments and monitoring: Monitoring is required for
assessing response and for side effects that may emerge. Further
assessments may be required during this period especially
if psychosocial treatments are being planned. Information
should be obtained from the patients, family members, and
other available sources. Frequency of contact will depend
on several factors such as clinical state, the distance of the
hospital from the patient’s home, social support available for
the patient, the type of treatment being administered etc.
Antipsychotic treatment
Dose: The dose of the antipsychotic needs to be
individualized. A balance has to be struck between the
need to reduce side effects and the need to prevent relapse.
Stable patients who do not have positive symptoms may
be candidates for reduction in doses. Doses need to be
reduced gradually at the rate of about 20% every 6 months
till a minimum effective dose is reached.
Reduction of dose/ withdrawal of antipsychotic medication
may be be undertaken gradually whilst regularly monitoring
signs and symptoms for evidence of potential relapse.
Following withdrawal from antipsychotic medication,
monitoring for signs and symptoms of potential relapse, need
to continue, for at least 2 years after the last acute episode.
Any re-emergence of symptoms is to be immediately treated.
Duration of treatment: Duration of treatment depends on
a number of factors and will need to be individualized. The
suggested guidelines are as follows:
• First-episode patients ought to receive 1-2 years of
maintenance treatment
• Patients with several episodes or exacerbations are to
receive maintenance treatment for 5 years or longer
after the last episode
• Patients with history of aggression or suicide attempts
should receive treatment for longer period or lifelong.
The usual indications for use of long term or lifelong
antipsychotic medications are shown in table-14.
Psychosocial interventions
The psychosocial interventions started in the previous
treatment phases is to be continued and the gains obtained
till now should be evaluated. Further, the clinicians should
evaluate as to whether any change is required in terms of
goals and strategies used.
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Table 14: Indications for life long/long term use of
antipsychotic medications
History of multiple relapses while on treatment
History of relapses when the medications are tapered off
History of 2 episodes in last 5 years
History of suicidal attempts
Presence of residual psychotic symptoms
Family history of psychosis with poor outcome
Comorbid substance dependence
Rehabilitation
Facilities for vocational rehabilitation are scarce. However,
if the patient is already working efforts can be made to help
out in any problems at the work place, which could be due
to the effects of the illness. If the patient is unemployed,
their suitability for work needs to be assessed. If he is
ready for work, he is to be encouraged to seek appropriate
jobs. However, if the patient requires rehabilitation then
culture-specific characteristics for that rehabilitation
programme need to be adopted in order to be successful.
Early intervention for relapses
The management plan needs to be organised to respond as
quickly as possible to any relapses in the patient’s condition.
Patients and relatives need to be educated to recognise early
symptoms of a relapse. They need to be told about the need
for early intervention in impending cases of relapse. They need
to have easy access to treatment facilities such as emergency
services or inpatient settings, which will cater to the needs
of a patient on the verge of a relapse. Contact need to be
increased during this phase. Crisis intervention measures
such as brief admissions or frequent home visits need to be
adopted, whenever feasible. All these are important steps in
efficient detection and treatment of relapses.
SPECIAL SITUATIONS
Clinicians often encounter certain clinical situations which
either require special attention or can influence treatment
decisions. Management of these situations is summarised
in table-15.
SIDE EFFECTS AND THIER MANAGEMENT
Antipsychotics are associated with many side effects, which
require intervention. Some of the common side effects that
can be very distressing to the patients include extrapyramidal
side effects, cardiovascular side effects, sexual dysfunction
and metabolic side effects. The cardiovascular side effects
can be life threatening too. The common management
strategies for these side effects are shown in table-16.
Extrapyramidal side effects: Extrapyramidal side effects
(EPS) are often noted in patients receiving FGAs, especially
high potency antipsychotic medications. However, EPS is
S28
also seen with SGAs. The acute EPS include acute dystonia,
pseudo-parkinsonism and akathisia. Acute EPS is usually
seen during the first few days or weeks of starting treatment,
is dose dependent and subsides with stoppage of offending
agent. Chronic EPS is usually seen after prolonged use
(months to years) of antipsychotics and these include
tardive dyskinesia, tardive dystonia and tardive akathisia. It
is important to note that chronic EPS is not dependent on
the dose of antipsychotics and persists even after stopping
the offending agent. It is important to be aware of the risk
factors for development of these side effects (table-17).
In case a patient is experiencing Parkinsonism during the
initial phase of treatment, the first step of management
involves lowering the dose of the antipsychotic medication.
If reduction in dose is associated with unacceptable efficacy
than change of antipsychotic medication may be considered.
When change of antipsychotic medication is considered, a
medication with lower EPS potential need to be opted. In
patients who respond to an antipsychotic and continue to
experience Parkinsonism, a short course of anticholinergic
medications may be considered.
Acute dystonia is also seen during the initial phase
of treatment, i.e., after receiving first few doses of
antipsychotics. Acute dystonias respond dramatically
to administration of parenteral anticholinergic or
antihistaminergic medications. Recurrence of acute
dystonias can also be prevented by using a short course of
anticholinergic medications.
First step in management of acute akathisia involves
reduction in dose or changing the antipsychotic to a
medication with lower EPS potential. Some patients
may require the use of medications like beta-blockers
and benzodiazepines like clonazepam or lorazepam for
management of akathisia.
Neuroleptic Malignant Syndrome (NMS): It is an acute
psychiatric emergency, which has been reported to occur more
often with FGAs. However, data in the form of case reports
and case series also suggest association of almost all SGAs with
development of NMS. Various factors which increase the risk
of NMS are shown in table-18. Management involves stopping
the antipsychotic medication, supportive measures and use of
bromocriptine, amantadine or dantrolene. Use of lorazepam
may also be helpful and those patients with NMS, who donot
respond to these treatments, may benefit with ECT.
Sedation: Many antipsychotics are known to cause sedation
by virtue of their antihista-minergic, antiadrenergic, and
anti-dopaminergic action. The risk of sedation is high with
chlorpromazine, clozapine and quetiapine. Initial strategy
should be to wait and watch and if this is not beneficial, if
possible dose reduction must be considered.
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Table 15: Issues related to special situations

Special situation Strategies
First‑episode • Longer duration of untreated psychosis is powerful predictors of subsequent poor outcome
psychosis and early • Attempts need to be made to reduce the duration of untreated psychosis, to promote remission through effective
intervention pharmacological and psychosocial interventions, to maximize functioning, and to prevent relapse and other adverse
outcomes
• Early detection, comprehensive assessment, emphasis on continued engagement, and flexible treatment enable early
intervention services to meet these goals
• It is still not clear for how long patients with first‑episode psychosis are to continue maintenance antipsychotic medication
• A 1‑2 year period is usually recommended, though many patients may require longer periods, and some may require shorter
periods of treatment
Suicidality in • Suicide is more common during the initial period after discharge from the hospital
schizophrenia • Risk factors which have been specifically associated with suicide among patients with schizophrenia include younger age,
high socio‑economic status, high premorbid scholastic achievement and high intelligence quotient, high aspirations and
expectations, early age of onset, younger age at first hospitalization, a chronic and deteriorating course with multiple relapses
and higher level of insight into the illness
• Some of the treatment related issues which have been shown to be associated with suicide include inadequate treatment, poor
medication adherence, poor response to treatment and akathisia
• As it is not possible to predict suicidal behaviour, clinicians need to pay greater attention to presence of suicidal ideations,
which are predictors of suicidal attempt and suicide at every phase of treatment
• High risk management need to be followed during the initial phase of admission and every effort need to be made to retain
the patient in the inpatient set‑up
• Adequate treatment of psychotic symptoms with antipsychotic medication and of depression when present with appropriate
therapy can prevent suicide
• Clozapine has been shown to reduce the risk for suicidal behaviours. Accordingly, it may be preferred for patients who have
multiple suicide attempts or persistently report suicidal ideations.
• Psychoeducation of patient and family need to focus on discussing about warning signs of suicide. Patients
experiencing severe distress due to a feeling of loss, stigma etc., need to be provided psychological support and
monitored closely.
Violence and • All patients are to be evaluated for violence and dangerousness during every assessment, especially during the acute phase of
Aggression in illness
Schizophrenia • Whenever a patient is found to have serious threat for violence or exhibits violence, inpatient management is to be
considered
• Injectable antipsychotics like haloperidol or lorazepam can be used for management of violence and aggression
Comorbid Substance • Presence of substance use disorder is often associated with overall poor outcome of illness
use Disorders • Clinicians also need to pay attention to these disorders and the additional aims of the treatment are abstinence from the
substances or at least harm reduction
• Pharmacological agents shown to be effective for management of detoxification and pharmaco‑prophylaxis for different
substance use disorders may be considered if required
• Psychosocial interventions like relapse prevention counselling, cognitive behavioural interventions and motivation
enhancement treatment may be included in the treatment plan
• Patients are to be continuously monitored for relapse of substance use disorder
Depression • A rational approach to treating depression in schizophrenia first needs to consider and rule out organic conditions, negative
symptoms, antipsychotic associated side effects (dysphoria, akinesia and akathisia), schizoaffective depression, stress‑related
reactions, and an impending psychotic episode
• Controlled trials with SGAs have shown that they are superior to FGAs in their antidepressant efficacy.
• Clozapine may be particularly effective in patients at high risk for suicide
• Antidepressants are generally ineffective during the acute phase. They may even worsen the psychosis, and are best
avoided
• On the other hand, results of controlled trials have demonstrated the efficacy of adjunctive antidepressant therapy in
post‑psychotic depression
• Clinical experience suggests that ECT may be helpful
Catatonia • Whenever a patient with schizophrenia presents with catatonia, all possible differential diagnosis for catatonia is to be
considered. Appropriate investigations may be carried out and the underlying causes are to be managed
• Initial management may involve use of benzodiazepines, especially lorazepam, which leads to symptomatic relief in
significant proportion of cases
• In case the catatonia does not respond to benzodiazepines or relapse after stopping benzodiazepines, ECT is to be
considered
Negative symptoms • First step in management of predominant negative symptoms is to rule out secondary negative symptoms. However, if
negative symptoms persist, they are presumed to be primary negative symptoms of the deficit state
• No treatments have proven efficacy for management of primary negative symptoms, although some benefit has been reported
with clozapine and amisulpride
• Psychosocial interventions in the form of social skill training, token economy may be attempted

Contd...

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Table 15: Contd...
Special situation Strategies
Obsessive • Obsessive compulsive disorder/Obsessive compulsive symptoms are common in patients with schizophrenia and these may
compulsive be part of the prodrome of schizophrenia, may be part of clinical manifestation of schizophrenia along with other symptoms,
symptoms in may be treatment emergent or may precede the onset of schizophrenia
schizophrenia • Treatment emergent obsessive compulsive symptoms are commonly reported with SGAs like clozapine, olanzapine and
risperidone
• There is little evidence in the form of randomized controlled trials for management of obsessive compulsive symptoms in
schizophrenia
• In general it is suggested that if the obsessive compulsive symptoms appear to be part and parcel of schizophrenia, initially
patients may be treated with antipsychotics only and the obsessive compulsive symptoms need to be monitored
• If the obsessive compulsive symptoms are considered to be treatment emergent then reduction in dose of antipsychotic,
change of antipsychotic or use of antiobsessional agents are to be considered
• Among the antiobsessional agents, there is some data for the efficacy of clomipramine and fluvoxamine
• Cognitive behaviour therapy in the form of exposure and response prevention has also been tried with beneficial effects
Comorbid Physical • Patients with schizophrenia have high rate of physical illnesses
illnesses • All patients need to receive thorough assessment for possible physical illnesses and depending on the feasibility may be
investigated as per the requirement
• Those with comorbid physical illnesses need to be continuously monitored during all the phases of treatment
• Comorbid physical illnesses and concomitant medications need to be taken into account while selecting the treatment setting
and antipsychotic medication per se
Treatment‑resistance • The first step in the management of treatment‑resistance is to establish that the disorder has failed to respond to adequate
schizophrenia (TRS) trials of antipsychotics in terms of dosage, duration and adherence
• Other causes of non‑response need to be considered such as, non‑compliance, adverse effects, comorbid conditions such as
substance misuse, before actually diagnosing treatment refractoriness
• Clozapine has been reported to be beneficial among patients with TRS
• The role of ECT in TRS has not been examined, although studies suggest that it could be useful
• Chosocial interventions such as cognitive therapy, family treatment, assertive outreach or crisis intervention are also
beneficial.
Clozapine – • There is some evidence to suggest that combining ECT with clozapine improves the outcome of patients who donot respond
resistance to clozapine alone
• Evidence for usefulness of combining clozapine with other antipsychotics, antidepressants, mood stabilizers is limited and
not convincing
Difficult to treat • Factors which make the patient difficult to treat include: inadequate response to antipsychotic, problems of adverse drug
schizophrenia effects, poor medication compliance, comorbidities, treatment failure and relapse on adequate drug dosages
• Issues related to medication compliance and adverse effects need to be addressed
• Antipsychotic need to be selected keeping the medical and psychiatric comorbidities in mind
• Patients with treatment resistance may be treated with clozapine.
• Patients having relapse of symptoms despite adequate dosages of 2 or more antipsychotics may also be treated with clozapine.
• Psychosocial factors influencing medication compliance need to be evaluated and addressed
Pregnancy • Many patients with schizophrenia have unplanned pregnancies and because of illness related variables, compared to those
without schizophrenia, women with schizophrenia more commonly have pregnancy outcomes in the form of low birth
weight, preterm birth, still birth and perinatal deaths
• Patients and caregivers need to be counselled about pregnancy and the risks and unplanned pregnancies may be avoided
• Most of the psychotropics belong to category ‘C’ or ‘D’, except for clozapine
• In general it is said that high potency antipsychotics have lower risk of foetal malformations
• Any decision to start antipsychotics, continue or discontinue antipsychotics need to take into account current level of
symptomatology, longitudinal course of symptoms, risk of relapse with stoppage of medication, effect of a particular
antipsychotic on foetal malformation and obstetrical complications
• All decisions about medications are to be taken after proper consultation with the patient, spouse and caregivers. A close
liaison with the obstetricians is helpful in monitoring patients during the pregnancy

Anticholinergic and antiadrenergic side effects: These
side effects manifest as dry mouth, blurred vision,
constipation, urinary retention, thermoregulatory effects,
impaired learning and memory and slowed cognition. Some
patient may develop confusion, delirium, somnolence and
hallucinations due to severe anticholinergic side effects.
Anticholinergic side effects are more commonly seen with
clozapine and chlorpromazine. It is reported that the
anticholinergic side effects are usually dose-dependent
and reduce with reduction in the dose of antipsychotic or
concomitantly used anticholinergic agent.
Cardiovascular side effects: Among the cardiac side effects, the
commonly encountered side effects include QTc prolongation,
orthostatic hypotension and tachycardia. QTc interval of
more than 500 milliseconds is associated with elevated risk
of ventricular arrhythmias, known as “torsades de pointes”,
which may lead to ventricular fibrillation and sudden cardiac
death. Among the older antipsychotics, thioridazine, pimozide
and high dose of intravenous haloperidol are reported to be
associated with increased risk of QTc prolongation. Among
the SGAs, ziprasidone is reported to have higher risk of
QTc prolongation; however, this has not been shown to be

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Table 16: Management of Side Effects of Antipsychotics

Side effect First Step Other options
Antipsychotic induced Parkinsonism Reduce the dose Change the antipsychotic to an antipsychotic with lower EPS
potential
Acute dystonia Parenteral ‑ anticholinergic or antihistaminergic Short term use of anticholinergics to prevent recurrence
medications
Acute Akathisia Reduce the dose Change the antipsychotic to an antipsychotic with lower EPS
potential
Use‑ beta‑blockers, benzodiazepines
Tardive dyskinesia Stop the offending agent Clozapine in case there is worsening of psychosis
Vitamin‑E, benzodiazepines, anticholinergics
Tardive dystonia Stop the offending agent Clozapine in case there is worsening of psychosis
Neuroleptic malignant syndrome Stop the offending agent In treatment refractory NMS consider ECT
Supportive measures
Bromocriptine, amantadine, dantrolene
Lorazepam
QTc prolongation Reduce the dose Stop the offending agent
Change the antipsychotic to an antipsychotic with lower
potential for QTc prolongation
Orthostatic hypotension Reduce the dose Stop the offending agent
Change to an antipsychotic with lower antiadrenergic or no
antiadrenergic activity
Use of stockings, increasing the salt intake, fludrocortisone
Tachycardia due to anticholinergic Wait and watch for sometime in those without Peripherally acting beta‑blockers
action cardiac disease
Hyperprolactinemia and Sexual Reduce the dose Change to an antipsychotic with lower potential to cause
dysfunction hyper‑prolactinemia
Consider use of bromocriptine or amantidine if there is
hyperprolactinemia
Sexual dysfunction not associated with
hyperprolactinemia‑ Yohimbine, Cyproheptadine,
Imipramine (for retrograde ejaculation), Phospho‑diaesterase
inhibitors (for erectile dysfunction), antidepressants like
paroxetine, dapoxetine (for premature ejaculation)
Sedation Wait and watch – most patients develop tolerance In case of persistent sedation
Reduce the dose
Change to night time dose, if using the medication in divided
doses
Change to a less sedating agent
Anticholinergic and antiadrenergic Stop concommitant anticholinergic agent if used Change to an antipsychotic with lower anticholinergic properties
side effects Reduce the dose Constipation‑ high fibre diet, increase water intake, laxatives
In case of severe side effect like delirium
stoppage of offending agent may be required

associated with sudden cardiac deaths. In case, there is QTc anticholinergic activity, as seen with clozapine may be
prolongation, change of antipsychotic is to be considered. managed with low dose peripherally acting beta-blockers.

Hypotension associated with various antipsychotics is attributed
to antiadrenergic activity. It is commonly seen with clozapine,
risperidone, quetiapine. Among the FGAs, hypotension is often
seen with chlorpromazine. Hypotension can be prevented
by starting with lower doses and slow upward titration of
medication. When a patient develops hypotension with a
particular antipsychotic medication, the first step in management
is to reduce the dose of the offending agent. If this does not
help than switching to another agent with lower antiadrenergic
activity is to be considered. Additional management strategies
include use of stockings, increasing the salt intake and use of
fludrocortisone, which is a fluid retaining corticosteroid.
Tachycardia may be associated with hypotension or it may
result due to anticholinergic activity. Tachycardia due to
Hyperprolactinemia and Sexual dysfunction: All antipsychotics
are shown to be associated with sexual dysfunction, although
the rates vary with different antipsychotics. In general, rates
of sexual dysfunction are reported to be higher with FGAs and
risperidone. One of the common causes for sexual dysfunction
with FGAs and risperidone is increase in prolactin levels,
which leads to disruption of hypothalamo-pituitary-gonadal
axis. Females have been reported to be more sensitive to
hyperprolactinemia related sexual dysfunction. First step in
management of hyperprolactinemia and sexual dysfunction
is reduction in the dose of antipsychotic medication. If this
option is not acceptable, change in antipsychotic is to be
considered. If change of antipsychotic is not possible, than
management with bromocriptine or amantidine may be
considered to lower the prolactin levels.

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Table 17: Risk factors for acute and tardive Monitoring for metabolic side effects: It is now well known
extrapyramidal side effects with antipsychotics that compared to subjects in the general population,
Acute Dystonia patients with schizophrenia have high rates of metabolic
Use of high potency FGAs syndrome. Higher prevalence of metabolic syndrome
Young age suggests that clinicians need to monitor the patients for
Male gender emergence of metabolic side effects and manage the same
High doses
Intramuscular administration of antipsychotic medications
to reduce the cardiovascular morbidity and mortality.
Acute Akathisia Antipsychotics have also been shown to increase the risk
Use of high potency FGAs of development of diabetes mellitus. Further evidence
Tardive dyskinesia suggests that there is some discriminatory effect of various
Older age
antipsychotic medications on metabolic profile. Clozapine
Female gender combined with postmenopausal status
Use of FGAs and olanzapine have been reported to be associated
Use of high doses of antipsychotic medications with highest risk for development of weight gain, lipid
Antipsychotic‑induced parkinsonism abnormalities and elevation in blood glucose levels (See
Concurrent general medical conditions like diabetes table-18).
Affective disorder (particularly major depressive disorder)
Tardive dystonia
Use of high potency FGAs Considering the metabolic side effects associated with
Neuroleptic Malignant syndrome antipsychotics, various guidelines have been proposed and
Young age there are certain variations in the proposed monitoring
Male gender frequency. In general it is suggested that patients need to
Use of high potency antipsychotic
be monitored for metabolic disturbances at baseline, at
Rapid increase in the dose of antipsychotic
Use of intramuscular preparation 4-6 weeks and 12 weeks after starting antipsychotic and
Acute agitation then after every 3 months or at least annually (table-19).
Preexisting neurological disability However, those who have personal and family history of
Comorbid physical illness obesity, diabetes mellitus, dyslipidemia, hypertension
Dehydration
and/or cardiovascular disease are to be monitored 3
monthly.
Table 18: Risk of Metabolic side effects associated with
various antipsychotic medications6 However, in Indian setting, due to poor follow-up rates and
Antipsychotic medications Risk of lipid and/or Risk of available resources, it may not be feasible to monitor all the
glucose metabolism weight gain parameters regularly. Efforts need to be made to monitor
abnormalities the weight and fasting blood glucose levels at every
FGAs treatment facility. Patients managed at training centres and
Chlorpromazine High (limited data) Substantial resourceful settings may consider complete monitoring of
Fluphenazine Low (limited data) Neutral/low metabolic parameters.
Haloperidol, Perphenazine Low Neutral/low
Thioridazine High (limited data) Intermediate
SGAs If a patient develops metabolic abnormalities, switching
Clozapine, Olanzapine High Substantial of antipsychotic may be considered. In general if a patient
Quetiapine Moderate Intermediate gains more than 7% of the baseline weight or develops
Risperidone, Iloperidone, Mild Intermediate hyperglycemia, hyperlipidemia, hypertension or any other
Paliperidone, Sertindole
Lurasidone Low (limited data) Intermediate
significant cardiovascular or metabolic side effect, then
Zotepine Not reported Intermediate a change in antipsychotic is to be considered. However,
Asenapine Low (limited data) Low while considering switching, clinicians need to take into
Amisulpride Mild Neutral/low consideration the entire course of the illness, comorbid
Ziprasidone, Aripiprazole Low Neutral/low
physical illnesses, side effect profile of medication which

Table 19: Monitoring for metabolic disturbance while receiving various antipsychotic medications
Baseline 6 weeks after starting 12 weeks after starting Atleast annually
antipsychotics antipsychotics thereafter
Medical History X
Weight/waist circumference/BMI X X X X
Blood Pressure X X X X
Fasting glucose levels X X X X
Fasting lipids X X X X
Lifestyle modification advise X X X X

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caused metabolic side effects and the potential side effects
with proposed medication to be used after switching. If
switching of antipsychotic is not possible then medications
like metformin or topiramate may be considered, along
with more intensive dietary and life style modifications. A
close liaison need to be maintained with endocrinologist
and cardiologist to provide best quality care to patients.
SUGGESTED READING
1. American Psychiatric Association. Practice guideline for the treatment of
patients with schizophrenia, second edition. Am J Psychiatry 2004; 161
(supplement):1-56.
2. Avasthi A, Agarwal M, Grover S, Khan MKR. Research on antipsychotics
in India. Indian J Psychiatry, 2010; 52 (Suppl): S317-340.
3. Chakrabarti S. Impact of Schizophrenia on caregivers: The Indian
Perspective. In: Schizophrenia: The Indian Scene. Eds (2nd edition):
P Kulhara, A Avasthi, S Grover. Published by PsyPROM, PGIMER,
Chandigarh, Chandika Press, Barwala, Haryana, 2010, pp 215-262.
4. Chakrabarti S. What’s in a name? Compliance, adherence and
concordance in chronic psychiatric disorders. World J Psychiatry 2014; 4:
30-36.
5. CRAG/SCOTMEG Working Group on Mental Illness. Services for people
affected by schizophrenia. A good practice statement. The Scottish Office.
National Health Service in Scotland, 1995.
6. De Hert M, Detraux J, Winkel R, Yu W, Correll CU. Metabolic and
cardiovascular adverse effectsassociated with antipsychotic drugs. Nat.
Rev. Endocrinol. 2012; 8: 114–126.
7. Expert Consensus Guidelines, LLC. Expert Consensus Guideline Series.
Treatment of Schizophrenia. Memphis, Physicians Postgraduate Press
Inc, 1999.
8. Gasquet I, Haro JM, Tcherny-Lessenot S, Chartier F, Lépine JP.
Remission in the outpatient care of schizophrenia: 3-year results from the
Schizophrenia Outpatients Health Outcomes (SOHO) study in France. Eur
Psychiatry. 2008;23:491-6.
9. Grover S, Avasthi A. Antipsychotic prescription pattern: a preliminary
survey of Psychiatrists in India. Indian J Psychiatry, 2010; 52: 257-259.
10. Grover S, Avasthi A. Mood Stabilizers in pregnancy. Indian J Psychiatry
2015; 57 (Suppl 2): 308-23.
11. Grover S, Avasthi A. Views about clinical practice guidelines of the Indian
Psychiatric Society: A survey of psychiatrists in India. Indian J Psychiatry
2009; 51: 127-33.
12. Grover S, Dutt A, Avasthi A. Indian Research: focus on Clozapine. Indian
J Psychiatry, 2010; 52:168-173.
13. Grover S, Hazari N, Kate N. Combined use of clozapine and ECT: A
review. ActaNeuropsychiatrica 2015; 27: 131-142.
14. Haro JM, Edgell ET, Frewer P, Alonso J, Jones PB on behalf of the
SOHO Study Group. The European Schizophrenia Outpatient Health
Outcomes Study: baseline findings across country and treatment.
ActaPsychiatrScand 2003;107(suppl. 416):1–9.
15. Haro JM, Edgell ET, Novick D, Alonso J, Kennedy L, Jones PB, Ratcliffe
M, Breier A. Effectiveness of antipsychotic treatment for schizophrenia:
6-month results of the Pan-European Schizophrenia Outpatient Health
Outcomes (SOHO) study. ActaPsychiatrScand 2005: 111: 220–231.
16. Haro JM, Novick D, Suarez D & Roca M: Antipsychotic treatment
discontinuation in previously untreated patients with schizophrenia:
36-month results from the SOHO study. J Psychiatr Res. 2009 ;43:265-73.
17. Hazari N, Kate N, Grover S. Clozapine and Tardive movement Disorders:
A review. Asian J Psychiatry 2013;6: 439-451.
18. Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM,
Markwick A & Lewis SW. Randomised controlled trial of effect on quality
of life of second- vs first generation antipsychotic drugs in schizophrenia:
Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study
(CUtLASS 1). Arch Gen Psychiatry 2006;63:1079-87.
19. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y,
Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M,
Dollfus S, López-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N,
Riecher-Rössler A &Grobbee DE; EUFEST study group. Effectiveness of
antipsychotic drugs in first-episode schizophrenia and schizophreniform
disorder: an open randomised clinical trial. Lancet. 2008;371
(9618):1085-97.
20. Kulhara P, Chakrabarti S, Avasthi A, Sharma A, Sharma S.
Psychoeducational intervention for caregivers of Indian patients with
schizophrenia: a randomised-controlled trial. ActaPsychiatr Scand.
2009;119(6):472-83.
Indian J Psychiatry 59 (Supplement 1), January 2017
21. Kulhara P, Chakrabarti S. Clinical Practice guidelines for management of
schizophrenia. In: Clinical Practice Guidelines for Psychiatrists in India
on Schizophrenia, depression, bipolar affective disorders, obsessive
compulsive disorder, Generalized anxiety disorder and panic disorder.
Eds: Gautam S, Avasthi A. Indian Psychiatric Society, 2005.
22. Kulhara P. Management of Schizophrenia: An Update. Indian J Psychiatry
1998;40: 120-134.
23. Larsen ER, Damkier P, Pedersen LH, Fenger-Gron J,
Mikkelsen RL, Nielsen RE, Linde VJ, Knudsen HED, Skaarup L,
Videbech P. Use of psychotropic drugs during pregnancy and breast-feeding.
ActaPsychiatrScand 2015: 132 (Suppl. 445): 1–28
24. Lehman AF, Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB,
Goldberg R, Green-Paden LD, Tenhula WN, Boerescu D, Tek C,
Sandson N, Steinwachs DM. The Schizophrenia Patient Outcomes
Research Team (PORT): updated treatment recommendations 2003.
Schizophr Bull 2004;30(2):193–217.
25. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO,
Kreyenbuhl J; American Psychiatric Association; Steering Committee on
Practice Guidelines. Practice guideline for the treatment of patients with
schizophrenia, second edition. Am J Psychiatry 2004;161(2 Suppl):1-56.
26. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation
versus first-generation antipsychotic drugs for schizophrenia: A
meta-analysis. Lancet. 2009;373:31-41.
27. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA,
Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J,
Hsiao JK. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)
Investigators Effectiveness of antipsychotic drugs in patients with chronic
schizophrenia. N Engl J Med. 2005 22;353:1209-23.
28. Lieberman JA, Stroup TS. The NIMH-CATIE Schizophrenia Study: what
did we learn? Am J Psychiatry. 2011;168:770-5.
29. Malhotra N, Grover S, Chakrabarti S, Kulhara P. Metabolic Syndrome
in Schizophrenia: A review.Indian J Psychological Medicine 2013; 35:
227-240.
30. McEvoy JP, Lieberman JA, Perkins DO, Hamer RM, Gu H, Lazarus A,
Sweitzer D, Olexy C, Weiden P, Strakowski SD. Efficacy and tolerability
of olanzapine, quetiapine, and risperidone in the treatment of early
psychosis: a randomized, double-blind 52-week comparison. Am J
Psychiatry 2007;164:1050-60.
31. McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY,
Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J,
Hsiao JK. Effectiveness of clozapine versus olanzapine, quetiapine, and
risperidone in patients with chronic schizophrenia who did not respond to
prior atypical antipsychotic treatment. Am J Psychiatry 2006;163:600–10.
32. McEvoy JP, Scheifler PL, Frances A. The Expert Consensus Guideline
Series: Treatment of Schizophrenia 1999. J Clin Psychiatry 1999;60
(Suppl 11).
33. Miller AL, Chiles JA, Chiles JK, Crismon ML, Rush AJ, Shon SP. The Texas
Medication Algorithm Project (TMAP) schizophrenia algorithms. J Clin
Psychiatry. 1999;60:649-57.
34. Nakajima S, Takeuchi H, Fervaha G, Plitman E, Chung JK, Caravaggio F,
Iwata Y, Mihashi Y, Gerretsen P, Remington G, Mulsant B, Graff-Guerrero A.
Comparative efficacy between clozapine and other atypical antipsychotics
on depressive symptoms in patients with schizophrenia: analysis of the
CATIE phase 2E data. Schizophr Res. 2015;161:429-33.
35. National Institute for Health and Care Excellence. Psychosis and
schizophrenia in adults: prevention and management Clinical guideline
(CG 178), 2014.
36. Novick D, Haro JM, Suarez D, Vieta E &Naber D: Recovery in the
outpatient setting: 36-month results from the Schizophrenia Outpatients
Health Outcomes (SOHO) study. Schizophr Res. 2009; 108:223-30.
37. Perkins DO, Gu H, Weiden PJ, McEvoy JP, HamerRM , Lieberman JA.
Comparison of Atypicals in First Episode study group Predictors of treatment
discontinuation and medication nonadherence in patients recovering
from a first episode of schizophrenia, schizophreniform disorder, or
schizoaffective disorder: a randomized, double-blind, flexible dose,
multicenter study. J Clin Psychiatry. 2008; 69:106-13.
38. Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM,
Capuano GA, Rosenheck RA, Keefe RS, Miller AL, Belz I, Hsiao JK.
Effectiveness of olanzapine, quetiapine, and risperidone in patients with
chronic schizophrenia after discontinuing perphenazine: a CATIE study.
Am J Psychiatry 2007;164(3):415–27.
39. Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck
RA, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK. Effectiveness
of olanzapine, quetiapine, risperidone, and ziprasidone in patients with
chronic schizophrenia following discontinuation of a previous atypical
antipsychotic. Am J Psychiatry 2006;163(4):611–22.
40. Suarez D, Haro JM. Overview of the findings from the European SOHO
study. Expert Rev Neurother. 2008; 8:873-80.
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CLINICAL PRACTICE GUIDELINES
Clinical Practice Guidelines for Management of Sexual Dysfunction
Ajit Avasthi, Sandeep Grover, T S Sathyanarayana Rao1
Department of Psychiatry, PGIMER, Chandigarh, 1Department of Psychiatry, JSS Medical College Hospital, JSS University,
Mysore
Participants of the Expert group on CPG for
management of sexual dysfunction
Murgesh Vaishnav, G Prasad Rao, Neelanjana Paul,
Mukesh P Jagiwala, Roop Sidana, M S Bhatia
INTRODUCTION
Sexual functioning is a complex bio-psycho-social process,
coordinated by the neurological, vascular and endocrine
systems. In addition to the biological factors, the psychosocial
factors like societal and religious beliefs, health status,
personal experience, ethnicity and socio-demographic
conditions, and psychological status of the person/couple
play an important role in adequate sexual functioning of a
person. In addition, sexual activity incorporates interpersonal
relationships, each partner bringing unique attitudes, needs
and responses into the coupling. A breakdown in any of
these areas may lead to sexual dysfunction.
Prevalence of sexual dysfunction in general population is
very high. It is suggested that about 43% of women and 31%
of men have one or other kind of sexual dysfunction. Among
men, premature ejaculation is the most common male
sexual dysfunction. There is lack of consensus with regards
to the most common sexual dysfunction in women with
some studies reporting hypoactive sexual desire disorder
to be the most common entity, followed by orgasmic
and arousal disorders; whereas other studies suggest
that difficulty achieving orgasm and vaginal dryness to be
the most common type of sexual dysfunction in women.
Problems of sexual dysfunction may be lifelong or acquired,
general or situational.
Address for correspondence:
Dr. Ajit Avasthi, Department of Psychiatry, Postgraduate
Institute of Medical Education and Research,
Chandigarh ‑ 160 012, India.
E-mail: drajitavasthi@yahoo.co.in
Access this article online
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Website:
www.indianjpsychiatry.org
DOI:
10.4103/0019-5545.196977
© 2017 Indian Journal of Psychiatry | Published by Wolters Kluwer ‑ Medknow
Although sexual problems are highly prevalent, these
are frequently under-recognized and under-diagnosed in
clinical practice. It is also noted that clinicians also have
lack of understanding about the approach for identification
and evaluation of sexual problem. It is often recommended
that the treating psychiatrists and collaborating specialists
need to possess broad knowledge and appropriate attitude
towards human sexuality.
The essential concepts underlying the management of sexual
problems are adoption of a patient-centered framework
for evaluation and treatment. Principles of evidence-based
medicine may be followed in both men and women in
diagnostic and treatment planning and adoption of common
management approaches for sexual dysfunction. The
purpose of these guidelines is to present a framework for the
evaluation, treatment, and follow-up of the patient/couple,
who presents with sexual dysfunction. We hope that these
guidelines would help in facilitating proper management of
patients presenting with various types of sexual dysfunction.
These guidelines are to be read along with the earlier version
of Indian Psychiatric Society Guidelines.
CLASSIFICATION OF SEXUAL DISORDERS
Compared to DSM-IVTR, DSM-5 has fewer categories
for describing sexual dysfunction and has provided
gender-specific sexual dysfunctions (Table-1). Other
major change in DSM-5 includes the duration criteria.
According to DSM-5 the minimum duration for making
the diagnosis of sexual dysfunction is 6 months (except
substance-/medication-induced sexual dysfunction) for
almost all the disorders and also specifies the frequency
of dysfunction to be 75-100%. DSM-5 has also done away
with the categories of sexual aversion disorder and sexual
dysfunction due to a general medical condition. The category
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How to cite this article: Avasthi A, Grover S, Sathyanarayana
Rao TS. Clinical Practice Guidelines for Management of Sexual
Dysfunction. Indian J Psychiatry 2017;59:91-115.
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Avasthi, et al.: Sexual dysfunction

Table 1: Comparison of diagnostic categories of ICD‑10 & DSM‑5 of sexual disorders

Disorders according to ICD‑10 DSM‑5
sexual cycle
Sexual desire disorders Lack or loss of sexual desire Male hypoactive sexual desire disorder
Sexual aversion Female sexual interest/arousal disorder
Excessive sexual drive
Sexual arousal Failure of genital response Male
disorders Erectile disorder
Orgasm disorders Orgasmic dysfunction Male
Lack of sexual enjoyment Premature (early) ejaculation
Premature ejaculation Delayed ejaculation
Female
Orgasmic disorder
Sexual pain disorders Nonorganic dyspareunia Female
Nonorganic Vaginismus Genito‑pelvic pain/penetration disorder
Substance/Medication induced sexual dysfunction
Other sexual disorders
Paraphilias Paraphilic disorders
Gender identity disorders Gender Dysphoria
Gender Dysphoria in children
Gender Dysphoria in adolescent and adults
Other specified Gender Dysphoria
Unspecified Gender dysphoria
Other sexual dysfunction, not caused by
organic disorder or disease
Unspecified sexual dysfunction, not
caused by organic disorder or disease

of substance induced sexual dysfunction is now labelled as Table 2: Subtypes of sexual dysfunctions according to
Substance/Medication induced sexual dysfunction. The Not DSM‑5
Otherwise Specified (NOS) category has also been removed. Subtypes
The substance or medication-induced sexual dysfunction has Onset Lifelong: present since the Acquired: develops after a period
been retained as such. Various types of sexual dysfunctions onset of sexual functioning of normal functioning
are categorized on the basis of onset and context (Table-2). Context Generalized : not limited to Situational: limited to certain types
certain types of stimulation, of stimulation, situation or partner
situation or partner
ICD-10 describes sexual disorders under the headings
of: Sexual dysfunction, not caused by organic disorder
or diseases (F52) under the broad heading of Behavioral sideward curvature of penis and watery semen. Thus, there
syndromes associated with physiological disturbances are exaggerated apprehensions in males centered on sexual
and physical disorders, Gender Identity disorders (F64), performance on “First wedding night (Suhaag raat)”. Some
Disorder of sexual preferences (F65), Psychological and of the studies have also shown that many females who have
behavioral disorders associated with sexual development leucorrhoea, for which no infective or pathological cause
and orientation (F66), under the broad heading of Disorders could be found have psychasthenic syndrome or female Dhat
of adult personality and behavior. syndrome, similar to Dhat syndrome in males.

Other sexual disorders/dysfunctions in Indian context
Although both the nosological systems have classified sexual
disorders, but they don’t include certain sexual disorders
commonly seen by Indian clinicians. Indian researchers have
consistently alluded to the existence of certain unique socio-
culturally determined sexual clinical conditions such as, Dhat
syndrome and Apprehension about potency. Dhat syndrome has
been coded in ICD-10 under other neurotic disorders (F48.8),
but the diagnosis of apprehension about potency doesn’t find
mention. The clinical entity of apprehension about potency
is related to the commonly held belief in most of the Indian
sub-cultures that masturbation and night emissions before
marriage result in loss of potency in marital conjugal relations.
Masturbation is considered to be responsible for shrinkage or
Sexuality is understood as a broader concept which goes
beyond sexual dysfunctions. These guidelines are applicable for
management of sexual dysfunctions and some of the disorders,
like Dhat syndrome which are seen in the Indian context and
are associated with high rates of comorbid sexual dysfunctions.
ASSESSMENT OF PATIENTS WITH SEXUAL
DYSFUNCTIONS
Evaluation of any patient with sexual dysfunction requires
thorough understanding about the type of sexual
dysfunction, factors associated with or contributing to
sexual dysfunction and factors maintaining the sexual
dysfunction. Accordingly, proper evaluation includes

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Avasthi, et al.: Sexual dysfunction

detailed history taking (sexual, medical and psychosocial),
focused physical examination, laboratory tests (routine
and specific) and consultation with appropriate specialists.
Careful attention always be paid to the presence of
significance comorbidities or underlying etiologies (e.g.,
cardiovascular disease, diabetes, depression).
Important aspects of evaluation of patients with sexual
dysfunctions
Discussing sex-related issues can be embarrassing both for
the clinician and the patient. Patients often carry the feeling
of failure or that they are abnormal. Clinicians should
anticipate the embarrassment of patient and acknowledge
that it could be difficult talking about such issues. For
example, the clinician may say, “Most people find it difficult
to talk about these things and may feel a bit embarrassed. I’d
just like to reassure you that everything you say is confidential
and that I’d like to help you if I can. The first step is to find out
exactly what’s going on so that we can figure out how to make
things right again. Please feel free to be open with me and to ask
questions whenever you have any doubt.” Some of the other
important issues for evaluation are given in Table-3.
The basic principles of sexual history taking are given in
table-4. The patient needs to be asked to describe their
problem in terms of time and manner of onset, its course
over the period, its current status, and associated medical
or psychological problems. While taking history, attention
must be given to features which can help in distinguishing
predominantly psychogenic from predominantly organic
sexual dysfunctions (Table-5). But, it is important to note
that, in many cases, organic and psychogenic factors may
coexist, particularly in individuals or couples with long-
standing or chronic sexual dysfunction. In such cases,
clinicians need to assess the independent and interactive
role of both organic and psychogenic factors.
An important aspect of sexual history taking in females is
to remember that women play different roles at different
times in their life. Many women have several roles-the
professional or worker, housewife, mother, daughter,
friend, and lover. It is often seen that the over the years
as the demands of other roles increase, lover role fades
away. Paying attention to these issues can be very useful,
and this information can be collected by using a process
called the “timetable of life.” Both partners can be asked
to fill in a timetable representing a typical week from their
initial interaction to the time of presentation. Various
aspects which can be covered during the assessment of a
week during a typical time frame may include, family time
(that is, with children and partners), work time (both at
work and work in the house), extended family time (with
parents and relations), social time, personal time, and
relationship time (time spent together as a couple). The
relationship time must also include information about the
sexual activity. A timetable almost always brings forward
various elements missing in the relationship and personal
time. Repeating the “timetable” for different times in life
and comparing it during courtship, when sexual desire
was probably good, with the timetable for a time when
sexual desire was low is useful and can show how priorities
change and how this influences desire for sexual activity.
Looking at what happens in a sexual situation often gives
much information about the defenses used when a patient
engages in sexual activity. Clinician may also note what
turns a patient on and off, how engorged he/she becomes
in the sexual experience, and whether loss of desire occurs
every time or it is situational. Other important aspects
which can enhance the understanding about the problem
include sexual fantasy, masturbation, genital functioning,
and contraception.
Psychosocial history: Psychological factors associated with
sexual dysfunction can be divided into three categories:

Table 3: Important aspects in evaluation of sexual dysfunctions

• Conduct the evaluation in a comfortable surroundings and ensure privacy
• Be empathic, non‑judgmental, and understanding
• Preferably use the language in which patient is comfortable
• Use neutral terms (as opposed to vulgar terms) and proper medical terms as long as these are in common usage (e.g., use `penis’ and `vagina’, but perhaps
`lips’ rather than `labia’)
• Use anatomical drawings to understand patients knowledge and explain sexual issues to the patient
• Reassure the patient that sexual dysfunction or adjustment problems are common and treatable. For example, “It is common for some people to .”
• Explain things in simple, clear and specific terms. Some patients may not be able to understand the language which is commonly used by clinicians and
may feel embarrassed to admit this. Hence, whenever new terms are used, provide alternatives or explanations. Check with the patients that they understand
the terms used.
• Start with general, non‑threatening questions first (e.g., “Do you have a regular partner?”) then ask more specific and potentially embarrassing
questions (e.g., “Do you also experience this problem when you masturbate, that is, when you touch or stimulate yourself?”).
• Assumptions must be avioded (e.g., sexual orientation, number of partners, sexual practices)
• If a couple has presented together, gather the information for a sexual history from each individual separately (i.e., not in each other’s presence).
• Conduct the evaluation in presence of a female attendant/relative while examining patients of opposite gender.
• Make sure that the `problem’ does not just reflect a lack of knowledge or unrealistic expectations on the part of the presenting individual or their partner.
• Understand the cultural and religious factors which influence sexual issues
• Although sexual dysfunction may occur in isolation, but in many cases there may be co‑existing problems contributing to the dysfunction (e.g., relationship
difficulties, psychiatric or physical illness) ‑ prioritize the treatment goals in such situations
• Assess psychological sophistication and motivation of the patient/couple

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Components
Basic goals of history taking
Basic questions in assessment
of sexual functioning for a
male
Past Treatment history
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Avasthi, et al.: Sexual dysfunction
Table 4: History taking for sexual disorders
Basic ingredients
• To understand the type of dysfunction and its cause
• To differentiate between potential organic and psychogenic causes in the etiology of a patient’s sexual problem
• To evaluate the potential role of underlying or comorbid medical conditions
• To assess the use of concomitant medications
LIBIDO/INTEREST
• Do you look forward to sex?
• Do you enjoy sexual activity?
• Do you fantasize about sex?
• Do you have sexual dreams?
• How easily are you sexually aroused (turned on)?
• How strong is your sex drive?
AROUSAL/PERFORMANCE
• When was the last time you had a satisfactory erection?
• How did you your problem start ‑ gradual or sudden?
• When did you have last normal erection?
• Do you experience morning or night time erections?
• Are you able to initiate an erection with sexual stimulation?
• Are you able to maintain an erection with sexual stimulation?
• Does your erectile dysfunction is related a specific partner or situation?
• Do you lose erection before penetration, or before climax?
• Do you have to concentrate to maintain an erection?
• Is there a significant bend in your penis?
• Do you experience pain while having erection?
• Do you have difficulty in certain sexual positions?
• Do you feel subjectively excited when you attempt intercourse?
• Does your vagina become sufficiently moist? (for females)
EJACULATION/ORGASM/SATISFACTION (males)
• Do you ejaculate when you have sex?
• Do you ejaculate when you masturbate?
• Do you ejaculate before you want to?
• How often you ejaculate before you want to?
• How often do you ejaculate before your partner wants you to?
• How does your partner react if you ejaculate before your partner wants you to?
• Do you take too long to ejaculate?
• Do you feel like nothing comes out?
• Do you experience pain with ejaculation?
• Do you see blood in your ejaculate?
• Do you have difficulty in reaching to orgasm?
• Is your orgasm satisfying?
• What percentages of sexual attempts are satisfactory to your partner?
ORGASM/SATISFACTION (females)
• Are orgasms absent and/or very delayed and/or markedly reduced in intensity?
• Is there adequate and acceptable stimulation with partner and/or with masturbation?
• Is the degree of trust and safety, you feel you need, present?
• Is there fear of letting go of control?
• What do you fear may happen that could be negative?
DYSPAREUNIA/VAGINISMUS (females)
• Where does it hurt?
• How would you describe the pain?
• When does the pain occur (with penile contact, once the penis is partially in, with full entry, after some
thrusting, after deep thrusting, with the partner’s ejaculation, after withdrawal, with subsequent micturation?)
• Does your body become tense when your partner is attempting, or you are attempting to insert his penis?
• What are your thoughts and feelings at this time?
• How long does the pain last?
• Does touching cause pain?
• Does it hurt when you wear tight clothes?
• Do other forms of penetration hurt (tampons, fingers)?
• Do you recognize the feeling of pelvic floor muscle tension during sexual contact?
• Do you recognize the feeling of pelvic floor muscle tension in other (non‑sexual) situations?
• Do you feel subjectively excited when you attempt intercourse?
• Does your vagina become sufficiently moist?
• Do you recognize the feeling of drying‑up?
Past treatment history for the presenting sexual problem‑local practitioners, Ayurvedic, Homeopathic, over the
counter medications, etc.
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predisposing factors, precipitating factors, and maintaining Table 5: Differentiating features between psychogenic
factors (See table-6), which can co-exist with each other. and organic sexual dysfunction
The areas to be explored in psychosocial history are enlisted Characteristics Predominantly Organic Predominantly
in table-7. It is to be remembered that the existence of Psychogenic
an organic disease does not rule out the possibility of a Age Older Younger
coexisting psychogenic factor. Conversely, the presence Onset Gradual (except trauma or surgery) Acute
of psychogenic conditions, such as anxiety, anger, guilt, or Circumstances Global Situational
Symptom Course Consistent or progressive Intermittent
marital discord, need not be considered as evidence for a
Desire Normal to start with Decreased
sole primary causation. Organic risks Present Absent, variable
Partner problem Usually Secondary Usually at the onset
The current psychological state need to be assessed with Anxiety and fear Usually Secondary Usually Primary
special focus on symptoms of anxiety or depression, low
self-esteem and coping skills, previous and current partner
Table 6: Psychological factors associated with sexual
relationships, history of sexual trauma/abuse, occupational
dysfunctions
and social stresses, socioeconomic status, and educational
Factors
level. Sexual dysfunction may affect the patient’s self-esteem
and coping ability, as well as his or her social relationships Predisposing • Restrictive upbringing
factors • Disturbed family relationships
and occupational performance. These aspects need to be • Traumatic early sexual experience
assessed in each case. Clinicians need not assume that • Inadequate sexual information
every patient is involved in a monogamous, heterosexual • Insecurity in the psychosexual role
relationship. • Distraction
Precipitating • Unreasonable expectations
factors • Random failure
Considering the fact that sexual problems arise in the • Discord in the relationship
interpersonal context, the clinician need to carefully assess • Dysfunction in the partner
past and present partner relationships. Another important • Infidelity
aspect of psychosexual history is inquiring specifically about • Reaction to organic disease
the quality of the relationship between the couple with respect • Pregnancy/Childbirth
• Poor emotional intimacy
to nonsexual factors, i.e., how to they get along on most issues, • Expectation of negative outcome
communication patterns, gender equality/inequality, level • Depression or anxiety
of commitment, dealing with stress, etc. While interviewing Maintaining • Performance anxiety
the couple together it is important to note the dynamics factors • Guilt
between the partners. Relationship problems may be due to • Poor communication
• Loss of attraction between partners
intrinsic differences between the two, and expectations about • Impaired self‑image
sexual fulfillment may also vary. Many a times, lack of proper • Restricted foreplay
communication between the couple, which may be due to • Poor emotional intimacy
embarrassment, may be mistaken as lack of caring. • Depression or anxiety
• Expectation of negative outcome
• Fear of intimacy
Another important aspect of psychosocial evaluation is the • Sexual myths and misconceptions
identification of patient/couple needs, expectations from • Poor communication
each other, priorities and treatment preferences. These may
be significantly influenced by cultural, social, ethnic and
religious perspectives. Patient education about the problem evaluated. While evaluating women careful medical history
is also important in enhancing therapeutic relationship, is to be obtained about any health problem that might
communication between patient and physician and ensuring affect sexual anatomy, the vascular system, the neurological
patient compliance. Partner involvement is important. On the system, and the endocrine system. Indirect causes i.e.,
first visit, it is not always possible to involve the partner but factors that cause chronic pain, fatigue, and malaise may
efforts need to be made to involve the patient’s partner early also contribute to dyspareunia.
in the treatment process at the earliest. If the psychosocial
assessment reveals the presence of significant psychological Substance use History: Excessive use of alcohol or use of
distress or conflict between the couple, further evaluation other recreational drugs may cause sexual dysfunction,
and management may be carried out either prior to, or along either by a direct effect on the penile neurovascular system
with treatment of sexual dysfunction. or by causing increased secretion of prolactin, reduction in
production of testosterone, or both.
Medical history: Historical events related to the presence of
chronic disease, use of pharmacological agents, endocrine Treatment/Medication History: Clinicians should also enquire
disorders, prior surgeries and trauma is to be carefully about the medication intake, including prescription drugs,

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Avasthi, et al.: Sexual dysfunction
Table 7: Psychosocial assessment of sexual dysfunctions
Variables Areas covered
Background • Marital history, Children, Educational level, Social
variables class, Occupation, Religious beliefs, family system
and relationships
Life style factors • Alcohol, Smoking, Opioids
Psychiatric history • Depression, Anxiety disorder
Sexual History
• Childhood and adolescent sexual learning and
activities
• Masturbation history, nocturnal emissions, Dhat,
Interpersonal sexual activity
• Breadth and flexibility of sexual script with all
partners
• “Time table of different phases of life”
Current sexual • Current masturbatory and interpersonal sexual
functioning activities
• Nature of the problem, onset, course, frequency
• Spontaneous sexual experiences (morning erections)
Relationship with • Harmony, Communication, Partner’s health
partner
Life stresses • Recent life stress, Current life stress, Losses
Expectations • Need, Expectations, Priorities, Treatment
from treatment preferences
over the counter medications and culturally sanctioned
aphrodisiacs. Medications commonly associated with sexual
dysfunction include diuretics (thiazides, spironolactone),
sympatholytics agents (Central agents like methyldopa ,
clonidine and peripheral agents like reserpine), alpha blockers,
beta blockers (particularly nonselective agents), angiotensin-
converting enzyme inhibitors, calcium channel blockers,
antipsychotics, antidepressants, benzodiazepines, buspirone,
lithium, disulfiram, digoxin, histamine H2-receptor blockers,
ketoconazole, niacin, phenobarbital, phenytoin, allopurinol,
gemfibrozil, clofiberate, phenobarbital, phenytoin, danazol,
GnRH agonists, oral contraceptives etc.
Physical Examination
Every effort be made to ensure the privacy, confidentiality
and personal comfort of the patient while conducting the
physical examination. Careful physical examination not only
corroborates the medical history but at times also reveals
unsuspected physical findings (e.g., decreased peripheral
pulses, vaginal atrophy, atrophic testes, penile plaque).
In addition, to the general and systemic evaluations, detailed
assessment of gonadal function, vascular competence,
neurological integrity, and genital organ normalcy is to
be performed on every patient. Patients suspected of
hypogonadism need to be assessed for evidence of muscle
development, size and structure of the penis, normal urethral
opening, hypospadias, size and consistency of the testes
and the prostate. Alcohol swabs can be used to test penile
temperature sensation. Bulbo-cavernosus reflex can be
elicited by squeezing the glans penis and assessing the evoked
contractions of external anal sphincter or bulbo-cavernosus
muscles. This reflex response is clinically detectable in 70% of
normal males. The penis also needs to be examined for evidence
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of any masses or plaque formation, angulation, unprovoked
persistent erection, or tight unretractable foreskin.
Similarly in females genital examination is often highly
informative, especially in cases of dyspareunia, vaginismus,
with a history of pelvic trauma and with any disease
potentially affecting genital health. If there are indications
from history, the opportunity for pap smear/sexually
transmitted disease investigation is to be taken.
Recommended Laboratory Testing
Recommended laboratory tests for men and women with
sexual problems typically include blood glucose levels,
cholesterol, lipids, hormonal profile and X-ray spine for spina
bifida. Additional laboratory tests (e.g., thyroid function)
may be performed at the discretion of the clinician, based
on the medical history and clinician’s judgment. When an
infective etiology for dyspareunia remains a possibility-
vaginal, cervical and vulval discharge microscopy/cultures
need to be performed.
Assessment of Knowledge and Attitude towards sex
Few patients may not actually have sexual dysfunction,
but may perceive the same, because of poor knowledge
and negativistic attitude towards sex. Further, in some
patients the sexual problems may be attributed to the
beliefs and cultural practices. Some of the scales like
Sexual Knowledge and Attitude Questionnaire and Dhat
syndrome Questionnaire, which have been validated in the
Indian context, may be used for structured assessment and
documentation. These scales can also help in determining
the area to be focused in sex education and psychoeducation.
Specialist Consultation and Referral
Patients with history of medical problems be referred to
appropriate specialty to evaluate the severity and state of
disease control (See table-8). Sometimes there may not be
a need for referral, but if patient requests for the same, it is
to be done. Further diagnostic evaluation also needs to be
conducted in case of lifelong or primary sexual dysfunction,
in the presence of specific anatomic or endocrine factors
and failure of initial therapy. Patients with hyposexual
desire and absent or retarded emission or anorgasmia may
need to be evaluated for the presence of diseases involving
the nervous system. Patients with prolonged or painful
erection need to be evaluated for the possibility of primary
penile disease, hematological disorder, or other systemic
diseases associated with penile complication.
By the end of assessment the clinician should be able to
answer the following questions for themselves to plan
management:
1. Does patient/couple actually have sexual dysfunction?
2. Whether the dysfunction is primarily psychogenic or
primarily organic?
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Avasthi, et al.: Sexual dysfunction
3. If the dysfunction has organic etiology, then is there a
psychological overlay too?
4. If there are more than one dysfunction, then which is
the primary?
5. Does patient has any comorbid psychiatric disorder?
6. If subject has a psychiatric disorder, then is the sexual
dysfunction secondary to it?
7. If subject has a psychiatric disorder, then how severe it
is?
8. Is there a marital discord between the couple, which
needs to be addressed?
9. What is the motivation of the patient/couple to seek
treatment?
10. What is the level of psychological sophistication?
MANAGEMENT OF SEXUAL DYSFUNCTION
Principles of management
Management of sexual dysfunction involves patient centered
approach and clinicians are expected to consciously adopt
the patient’s perspective and respect the ideas, feelings,
expectations and values of their patients. Some of the basic
principles of patient centered approach are given in Table-9.
Formulation: After complete assessment, the first step in
the management is to provide the patient/couple a brief
and simple account of the nature of their problems and
possible contributory factors. The aims of the formulation
are threefold. First, it helps the couple to understand their
difficulties. This can be a source of encouragement, especially
if the therapist also explains how common such problems are.
Second, the therapist point out the likely contributory factors,
particularly the maintaining factors which will be the focus
of therapy, and thus establish a rationale for the treatment
approach. Finally, providing a formulation also helps to check
that the information obtained during the assessment has
been correctly interpreted. So the couples need to be always
asked to give a feedback of the formulation.
Balancing the partners: It is important for the therapist to
understand the contribution of individual partner to the
problem and need to strike a balance between individual
partners. The therapist must emphasize the need of
collaboration between the partners for the success of the
therapy. The therapist needs to emphasize positive aspects
of the couple’s relationship.
Treatment options: Treatments for various sexual
dysfunctions can be broadly classified into general
and specific measures. The general measures include
sex education and relaxation exercises. The specific
measures can be either pharmacological measures, non-
pharmacological measures or a combination of both.
Among the non-pharmacological measures, many types of
psychotherapies like psychodynamic, interpersonal, rational
Indian J Psychiatry 59 (Supplement 1), January 2017
emotive therapy, Master Johnson’s behavioural therapy or
its modifications, systematic desensitization, ban on sexual
intercourse and skill training in communication of sexual
preferences etc have been used. Unfortunately there are no
well designed studies which have evaluated the effectiveness
of these psychotherapies. Most of the studies done have
used convenience sampling, don’t describe their sample
adequately, have not used standard definitions for various
disorders and are silent about the therapist variables. Hence
the results cannot be generalized. Among all the techniques,
which have been used, cognitive behavioural measures of
Master Johnson or its modifications are the most popular
and have been found to be most useful.
Selection of treatment: The final selection of treatment is to
be according to patient/couple’s choice. The therapist needs
to inform the patient/couple about the available modalities
and help them to make a reasoned choice. Agreed treatment
goals need to be established at the start of treatment.
Figure-1 and 2 shows the general outline for management
of cases of sexual dysfunction presenting with or without
psychiatric comorbidity. Initial evaluation involves detailed
psychosexual history and getting the basic investigations.
Besides taking a proper history ,screening questionnaires
can be used to assess the sexual knowledge and attitude.
The initial evaluation will help in ascertaining the type(s) of
sexual dysfunction. The next step involves establishing the
probable etiological basis of the dysfunction, i.e., whether
the dysfunction is organic in origin, psychological in origin
or has components of both. If the dysfunction is organic in
origin the patient is to be referred to the concerned specialists
and need to be investigated and treated accordingly. It is
often seen that some patients may have sexual dysfunction
of organic origin, but would also have psychological factors
contributing to its maintenance. Such patients are the most
difficult to treat and require very good liaison between
the psychiatrist and the physicians. In patients who have
psychogenic sexual dysfunction, the next step involves
evaluation for sexual knowledge, relationship issues,
presence of comorbid psychiatric disorder, motivation and
psychological sophistication of the patient for treatment.
Assessing the sexual knowledge and relationship issues
are important aspect of treatment of sexual dysfunction as
many a time the patient/couple may not have any sexual
dysfunction per se but the reported complaints may be
arising due to faulty beliefs or relationship issues. If any of
these two factors are found to be contributing to the sexual
dysfunction, these need to be focused and once they have
been adequately addressed, the sexual dysfunction is to be
reassessed and if present needs to be treated adequately.
If comorbid psychiatric disorder is present, the next step
involves ascertaining – is it primary or secondary (primary-
psychiatric disorder causing sexual dysfunction; secondary –
psychiatric disorder is secondary to sexual dysfunction). The
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Table 8: Medical history, physical examination and investigations for sexual dysfunctions
Components Basic ingredients
Medical History • Cancer (bladder, prostate, uterus, cervix, rectum or other)
• Chronic fatigue or weakness
• Diabetes mellitus
• Heart disease (heart attack, chest pain with exercise or sex)
• Hormone problems (testosterone, thyroid, steroids)
• Hyperlipidemia (elevated cholesterol or triglycerides)
• Hypertension
• Joint pains (severe or chronic problems moving or changing positions)
• Kidney disease
• Neurological problems (Parkinson’s Disease, multiple sclerosis, spinal injury)
• Prostate problems
• Radiation therapy to bladder, prostate, uterus or rectum
• Sexually transmitted diseases
• Sleep apnea (severe snoring, daytime sleepiness)
• Trauma or injury to: penis, pelvis, perineum, testes, uterus or rectum
• Unexplained weight loss
• Urinary problems (urgency, frequency, hesitancy, weak stream, infection)
• Vascular disease (stroke, mini‑stroke, blockage of arteries, aneurysms)
Treatment history • Current medications for physical illnesses
Psychiatric history • Diagnosis, severity of current symptoms, treatment
Physical examination • Complete physical examination
• General physical examination to look for evidence of cardiovascular, neurological diseases
• Complete genital exam
• Secondary sexual characteristics (e.g., gynecomastia)
• Body hair, fat distribution
• Blood pressure, heart rate, peripheral pulses, edema
• Vibratory sensation
• Lower extremity strength and coordination
Investigations • Heamogram
• Renal function test, Liver function test
• Fasting blood sugar
• Hormonal studies‑ FSH, LH, Prolactin, testosterone
• X‑ray spine for spina bifida
• Lipid Profile
• Penile Doppler
Special investigations • Nocturnal penile tumescence and rigidity testing
• Penile tumescence monitoring (Nocturnal penile tumescence (NPT) monitoring evaluates the presence or absence of the
involuntary unconscious erections, which normally occur during the REM stages of sleep, during 1-3 nights. Normal
nocturnal tumescence has been defined as a total night erection time greater than 90 min and an increase in penis
circumference in excess of 2 cm. A change in circumference of 16 mm or 80% of a full erection is thought to reflect a
sufficient degree of penile rigidity for vaginal intromission)
• Estimation of structural abnormalities of penis (penile biopsy, penile imaging, electrical activity of corpus cavernosum
• Penile angiography, radionuclear scintigraphy and measurement of cavernous oxygen tension
• Neurological investigations [biothesiometry (assesses vibration perception threshold), dorsal nerve conduction velocity,
bulbocavernosus reflex (sacral reflex arc) latency, Pudendal nerve somatosensory (genitocerebral)‑evoked potential and
Perineal electromyography.
Assessment of Knowledge • Sexual Knowledge and Attitude Questionnaire
and Attitude towards sex • Dhat syndrome Questionnaire‑ available in 10 Indian languages which can be completed by the patients themselves
Relationship issues • General relationship between the couple, marital discord etc
Indications for • Patient request
referral to urologist/ • Primary ED (poorly sustained erections, lifelong)
Gynecologist/ • Anatomic penile deformities ‑ Peyronie’s Disease, hypospadias, chordee, Phimosis, Short penis, buried penis
Endocrinologist • Pelvic/perineal trauma
• Endocrinopathy
• Complex vascular problems
• Complex neurologic problems
• Vaginismus/Dyspareunia

patient who have primary comorbid psychiatric dysfunction treatment of sexual dysfunctions. While treating these
or those who have prominent psychiatric symptoms (may disorders adequate care needs to be taken in selecting
be secondary in origin), the psychiatric disorders is to the pharmacological agent, so that the dysfunction is not
be treated first and adequately before focusing on the worsened. In some cases the side effects of the drugs can in

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Patient presenting with sexual dysfunction

• Detailed psychosexual history

• Use questionnaires to assess the sexual knowledge & attitude
• Get the basic investigations done

Ascertain that the sexual dysfunction is not due to poor

sexual knowledge or poor relationship between the couple

Treat marital discord Ascertain that the sexual dysfunction is Sex Education
prior to treatment of not due to poor sexual knowledge or & reassess for
sexual dysfunction poor relationship between the couple the diagnosis

• Ascertain the type of sexual dysfunction

• Try to ascertain whether it is due to organic or psychological causes

Etiology- psychological in nature

Assess for comorbid psychiatric disorders

Etiology organic in Comorbid psychiatric Comorbid psychiatric

nature disorders present disorders absent

Refer to concerned specialist Follow figure-3 Assess motivation and

(Endocrinologist, Urologist, psychological sophistication
and Gynecologist)

Motivation low/ inadequate

psychological sophistication Motivation high/ adequate
psychological sophistication

Start with Pharmacotherapy; Manage with combination of non-

motivate the patient for non- pharmacological &
pharmacological management pharmacological measures

Figure 1: Treatment Algorithm for Evaluation & Management of a case of Sexual dysfunction

Table 9: Principles of treatment is to be treated first. An important aspect of treatment

• Inform the patient about all the available choices and guide them make a
choice
• Provide information to the patient in an unbiased manner about different
treatment options, their pros and cons
• Select the treatment as per the patient’s choice
• Provide adequate information about the treatment selected, including
advice on what to do and whom to contact in case of side effects,
problems and complications
• Do not deny treatment in case patient does not have a partner or is not
able to bring the partner
• Document the mutually agreed treatment goals
fact help in decreasing/ameliorating the sexual dysfunction,
for example, for a case of depression with premature
ejaculation selective serotonin reuptake inhibitors like
paroxetine may be beneficial. If the psychiatric disorder is
secondary and not prominent then the sexual dysfunction
involves understanding the motivation and psychological
sophistication. If the motivation for treatment is low or
if patient has poor psychological sophistication, then the
primary mode of treatment is pharmacotherapy. Patients
who are highly motivated and/or have good psychological
sophistication are to be treated with combination of non-
pharmacological and pharmacological therapies.
General Non-pharmacological measures: Education about
sexuality
The first step in the treatment of any sexual dysfunction
is sex education/psychoeducation. The sex education needs
to aim at normalization of the individual’s experiences
and reduce anxiety about sex by providing accurate
information. The various components of sex education are
shown in Table-10. Although all the areas are to be covered,

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Patients presenting with sexual dysfunction & comorbid

psychiatric disorder

• Assess whether comorbidity is primary (psychiatric disorder causing sexual

dysfunction) or secondary (Psychiatric disorder is secondary to sexual
dysfunction)
• Assess the Severity of the comorbid disorder

Secondary
Primary or Secondary But
Prominent But Not prominent
Prominent

Treat sexual
dysfunction first

Intensive therapy based on

comorbid diagnosis

Assess motivation and

psychological sophistication

Select Pharmacotherapy taking into

consideration- severity of the disorder & type
of sexual dysfunction e.g. for a case of
Depression with PME give SSRIs or TCA;
Depression with ED give Trazodone

Motivation low/ inadequate Motivation high/ adequate

psychological sophistication psychological sophistication

Start with Pharmacotherapy;

Manage with non-
motivate the patient for non-
pharmacological measure ±
pharmacological management
Pharmacotherapy

Figure 2: Assessment and Management Algorithm for a case of sexual dysfunction with psychiatric comorbidity

special emphasis needs to be given to those areas, which
are directly related to the patient’s problem. Where ever
possible figures and diagrams are to be used for reference
and illustrations. In some cases the reading material can
also be provided to the couple/patient. Sex education and
teaching relaxation is to be carried out over about four
sessions.
General Non-pharmacological measures: Relaxation
exercises
Relaxation therapy should be taught to patient using
Jacobson’s Progressive Muscular Relaxation Technique or
Benson Henry Relaxation Technique. This can be combined
with the biofeedback machine so as to facilitate objective
evidence and mastering of anxiety by the patient.

Understand and clarify sexual myths: For some individuals,
inappropriate sexual beliefs or myths can cause problems
within a relationship. Individuals acquire expectations
about what sex should be like and how they or their partner
should behave. One of the components of sex-education is
to help the individual and his or her partner alter any sexual
beliefs that interfere with the individual’s enjoyment of sex.
Some of these apply equally to both men and women, while
others will be more relevant to one gender than the other.
Some of the common myths are given in Table-11.
Specific Non-pharmacological management of Sexual
Dysfunction
The specific non-pharmacological measures will vary according
to the type of sexual dysfunction. However, one of the
important components, of the specific measures includes home
work assignment for the couple. It is important to remember
that many of these measures are carried out simultaneously.
Homework assignment for the couple: The homework
assignment provides a structured approach, which allows

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Table 10: Aims and Components of education about sexuality

Aims of Sex Education
• Normalize the individual’s experiences (i.e., help the individual realize that there are many others who have the same needs, problems, and experiences)
• Reduce anxiety about sex by providing accurate information about arousal and normal sexual response, clarify sexual myths and dispel unrealistic
expectations
Components of Sex Education
• Discuss about anatomy of the sex organs
• Discuss about menstrual cycle, pregnancy, puberty, masturbation, formation of semen, nightfalls, types of sex, stages of sexual intercourse, normal male
and female sexual response cycle
• Educate the patient/couple about the wide variation in the extent and frequency of feelings of sexual desire from one individual to the next
• Educate patient/couple about the importance of the timing of sex. The time of day that suits one partner may not suit the other. Help the couple plan their
time so that they have regular blocks of time alone in which they can relax, enjoy each other’s company, and engage in sexual play if desired
• Educate the couple as to how to communicate with each other to express the desire for sex
• Educate partners about how to refuse sex diplomatically
• Educate patient/couple that sex will sometimes be refused and that the refusal is not necessarily an insult or a personal rebuff
• If culturally appropriate, encourage partners to accept the use of masturbation or manual stimulation if sexual advances are refused
• Remind couples that masturbation does not represent a lack of love or desire for one’s partner
• Assist shy or reluctant partners with learning to initiate sex more frequently
• Educate patient/couple about the fact that sexual desire levels fluctuate over the life span
• Encourage patient/couple to communicate their needs for desire and sexual arousal
• Encourage patient/couple to show each other what sort of stimulation is required for orgasm to occur (e.g., manual or oral stimulation)
• Educate males that some females may be able to have multiple orgasms (especially if a vibrator is used) and hence may sometimes find it pleasurable if
genital stimulation is continued after the initial orgasm
• Encourage patient/couple to talk about what kinds of caresses they do and do not like immediately before, during, or after orgasm (e.g., genital
stimulation after orgasm may be unpleasant)

Table 11: Common Myths about Sex this stage is to help the partners develop a sense of trust
• The man should be the sexual leader and closeness, to become more aware of what each one likes
• Masturbation is wrong and to encourage communication. Details of the procedural
• A woman should not initiate sex aspect of non-genital sensate focus session are given in
• Men should not express their emotions
Table-13. It is to be explained to the couple that they need
• A woman should always have sex when her partner makes sexual
approaches to “refrain from sexual intercourse and touching of each
• All physical contact must lead to sex other’s genitalia and the women’s breast” to ensure that they
• Good sex leads to a wild orgasm are not continually confronted by those aspects of sexuality
• A man feels like having sex at any time
that is most likely to cause anxiety, and to enable them to
• Sex equals intercourse
• Sex happens automatically concentrate on rebuilding their physical relationship by first
• A `respectable’ woman should not enjoy sex too much and should learning to enjoy general physical contact. Initial reactions
certainly never masturbate to these sessions vary according to the nature of the couple’s
• All other couples have sex several times a week; have orgasm every time problem. Some couple’s may find this enjoyable and others
they have sex & orgasm simultaneously
• There must be something wrong with the relationship if sex is not good
may react negatively. In some cases it will be appropriate for
• Cultural beliefs about formation of Semen and genital secretions the therapist to just acknowledge the problem and reassure
• Role of ‘Physical strength’ or ‘Muscle power’ in sexual performance and encourage the couple. In some cases therapist have to
• Size of the penis explain that this is understandable and expected, but that in
• Circumcision and sexual performance
• Bending of Penis
order to overcome a sexual problem like theirs it is necessary
• Vasectomy/tubectomy decreases sexual potency to approach it in a systemic fashion and with due course of
• Drugs enhance sexual potency in normal persons time they will begin to get pleasure out of their sessions and
• Porn increases sexual drive these would come as spontaneous behaviour.

the couple to rebuild their sexual relationship gradually. The
stages of this programme are labeled using the terminology
introduced by Master and Johnson (1970) is: non-genital
sensate focus, genital sensate focus and vaginal containment.
There are some basic principles of giving and carrying out
the homework assignments as shown in table-12.
Non-genital sensate focus: This assignment is particularly
helpful for a couple to establish physical intimacy in
a comfortable and relaxed fashion, and allows open
communication about feelings and desires. The basis aim of
Indian J Psychiatry 59 (Supplement 1), January 2017
Some couples will have more serious difficulties in the form
of negative responses to homework assignments, persistent
breaking of the ban on sexual intercourse, or cessation of
homework assignments. In such cases the focus of therapy
might have to be changed temporarily and sessions may
be required to help the partners express their feelings and
anxieties. In occasional cases no progress can be made in
developing understanding of why couple is encountering
difficulties. In such cases it is worth seeing the partners
separately to find out whether important information is
being withheld by one of them.
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Genital sensate focus: The couples, who go through the
non-genital sensate focus sessions successfully, need to
be told to move to the genital sensate focus sessions.
The aim and procedural aspect of genital sensate focus
are given in Table-14. As with the non-genital sensate
focus, some couples immediately find these sessions
pleasurable while others would react adversely. This
stage is particularly likely to generate anxiety, especially
about sexual arousal or intimacy, so it is very important
that the therapist specifically encourages partners to
focus on pleasurable sensations. Some of the techniques
for dealing with specific dysfunctions also need to be
introduced at this stage.
Table 12: Principles of giving and carrying out the
homework assignments
Components and goals of Homework Assignments:
• Aid in identification of specific factors (cognitions, attitudes), which
may be maintaining the sexual dysfunction
• The homework assignments also provides the couple the specific
techniques to deal with particular problems
Important Procedural Aspects of Homework Assignments
• The instruction need to be detailed and precise
• The therapist need to always check that the couple have fully registered
and understood the instructions before the treatment session ends
• When giving instructions the therapist needs to ask the couple how
they feel about the instructions and do they anticipate any difficulty. If
problems are anticipated, the therapist need to endeavor to resolve their
fears before they attempt the assignment
• A couple need not be asked to move to next stage of the programme
until they have mastered the current assignments
• A couple should never be left with the option of moving from one stage
to the next between treatment sessions depending on how they progress,
because uncertainty can be detrimental
• The couple need to be informed that the therapist will be asking for the
detail feedback on the progress at the next treatment session
Vaginal Containment: This stage is an intermediate one
in the introduction of sexual intercourse to the therapy
programme. It is relatively minor stage for couples whose
difficulties have by now largely resolved. For others it is
extremely important, especially when vaginal penetration
is the key step (e.g. ED, PME, and vaginismus). The couple
is instructed that when they both are feeling relaxed and
sexually aroused the women can introduce her partner’s
penis into her vagina and the partner to then lie still,
concentrating on any pleasant genital sensations. The best
position to attempt vaginal containment is female superior
position or a side to side position. The couple be asked to
maintain containment as long as they wish, and then they
can return to genital and non-genital pleasuring. The couple
can repeat the containment up to three times in any one
session. Once this stage is well established the couple to
introduce movement during containment, with preferably
women starting the movements first. With this the general
programme of sex therapy is completed and now the
treatment need to include superimposition of treatment for
specific sexual dysfunctions.
It is important to remember that during the whole therapy
feedback be taken after every session and any doubts/
misconceptions be clarified.
Home work assignments for single male
Management of sexual dysfunctions in single males also
involves same principles. The subject be provided with sex
education and thought relaxation exercises. The principles
of home work assignments for single male with erectile
dysfunction and premature ejaculation are given in Table-15
and Table-16. At the end the patient be counseled and
reassured that he can now indulge in heterosexual experience

Table 13: Non‑Genital Sensate Focus

Aims of non‑genital sensate focus
• To help the partners develop a sense of trust and closeness, to become more aware of what each one likes and to encourage communication
Frequency of homework sessions per week
• Do not impose a too rigid schedule, but make it clear to the couple that they should at least practice 3 sessions of homework per week
Procedural Aspect of non‑genital sensate focus
• One partner inviting the other partner for a home‑work session by giving explicit invitation
• Other partner should accept the invitation if he or she is feeling either positive or neutral about it. If the feeling is negative, it is important that the partner
conveys the same with explanation about such feeling
• Invitation by the partner who did not initiate at the first instance
Caressing session: don’ts
• Refrain from sexual intercourse
• Refrain from touching of each other’s genitalias and the women’s breast
Caressing session: do’s
• Can occur wherever the couple wishes, as long as they feel comfortable (but need to avoid becoming bored), warm and there is no risk of them being
disturbed
• Need to do in a way that gives pleasure to both of them
• During the early sessions this exercise need to be like a massage
• Need to begin with one partner exploring and caressing the other partner’s body all over, except for ‘no‑go’ areas
• The partners need to swap round when they wish to, so that the passive partner now takes over caressing
• During the caressing the passive partner need to focus on the sensations elicited by the caressing and need to provide feedback on what he/she likes and
dislikes and how things could be improved
• If any of the partner becomes sexually aroused during this stage, they need to enjoy this but need not go beyond the agreed limits of caressing
• There is no restriction to self‑masturbation if any partner wishes to, for relieving the sexual tension, but not to be done in presence of the partner

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without difficulty. However, he be cautioned that it should be
done after few days, not in a hurry, and to be carried out in
familiar surroundings without guilt or fear and anxiety.
ERECTILE DYSFUNCTION
An important aspect of assessment of erectile dysfunction
is to distinguish between psychogenic and organic erectile
dysfunction (See table-17). Non-pharmacological measures
are to be used in patients with psychogenic or mixed
erectile dysfunction along with pharmacological agents.
Specific Non Pharmacological treatment for erectile
dysfunction
Men with psychogenic erectile dysfunction will usually
start experiencing erections during either non-genital or
Table 14: Genital Sensate Focus
Aims of genital sensate focus
• To make the couples caressing more sexual and arousing and also to
encourage them to continue discussing their feelings and desires
Procedural Aspect of genital sensate focus
• Continue with pattern of alternate inviting and taking turns at caressing,
but to extend this to include both partner’s genitalia and women’s breast
• Emphasize the need for this stage to be added to the previous one, and
not to replace it
• Taking turns of being active and passive need to continue
Caressing session: do’s
• Caressing need to be initially gentle and exploratory, without sexual
arousal being the objective; if any of the partners becomes sexually
aroused during this stage, they need to enjoy this
• Guiding the partners hand can again be a useful means of helping the
partner learn what is enjoyable
• Lotions can also be used if the couple wishes
• If either partner wish to experience orgasm they may feel free to do so,
but this is not to be the goal of the session
Table 15: Home work assignments for Single Male with
Erectile Dysfunction
Home work Assignment
• Read erotic material, or see erotic material in books/movies and to note
the sense of sexual pleasure out of the same and to focus on it
• In subsequent sessions patient is asked to be alone and imagine about
the content of erotic material
• In subsequent sessions, patient also need to be asked to visualize, as far
as possible, of being involved in the same erotic/sexual activity
• If patient perceives erection, he shouldn’t get anxious or excited about
the same and need to continue to concentrate on the erotic stimuli and
related pleasure
• In later sessions patient is advised to combine reading of and seeing
erotic material with his fantasy and to focus on himself in foreplay and
later, intercourse
• In subsequent sessions, reading, seeing and fantasizing is to be
combined with fondling of penis and additional masturbatory hand
movements on the penis by using non‑dominant hand
• Terminate masturbation before the desire for ejaculation
• At the end of the therapy the patient is instructed to fantasize about
himself indulging in sexual intercourse with the process of ejaculation
and orgasm
Don’ts to be followed during the initial sessions
• Not to look for the erection
• Not to note the extent of erection, if any
Indian J Psychiatry 59 (Supplement 1), January 2017
genital sensate focus. If the therapist suggests that during
the initial phase the man tries not to have an erection this
can have the opposite effect. Men with erectile dysfunction
often have difficulty attending to erotic stimuli, especially
when an erection develops, tending instead to think about
the quality of their erection or whether they will be able to
maintain it. The therapist need to specifically encourage the
man to focus his attention on the pleasurable sensations he
experiences during the partner’s genital caressing (the use
of a lotion can often heighten these sensations), areas of his
partner’s body that he finds arousing, and the pleasure of
witnessing his partner’s sexual arousal.
Pharmacological treatment for erectile dysfunction
Besides the psychological measures, other therapeutic
options for erectile dysfunction includes medications,
constriction ring, vacuum constriction devices, intra-
cavernosal injections, intra-uretheral medication devices,
penile prosthesis and reconstructive surgery (Table-18).
Oral erectogenic agents
Oral therapy with vasoactive agents has emerged as the
first line treatment and has transformed the management
of erectile dysfunction.
Phospho-diaesterase inhibitors (PDE-5 inhibitors), i.e.,
sildenafil, tadalafil, vardenafil have proven efficacy and
safety in men with erectile dysfunction and are considered
as first line pharmacotherapy for management of erectile
dysfunction. The profile of these drugs is shown in
table-19. Among the available PDE-5 inhibitors, sildenafil
and vardenafil have short half-life, whereas tadalafil have
relatively longer half-life. Available data also suggests the
safety of some of these PDE-5 inhibitors in patients with
erectile dysfunction associated with diabetes mellitus,
spinal cord injury, chronic renal failure, Parkinson’s disease,
antidepressant use and following radical prostatectomy. It
is important to remember that action of PDE-5 inhibitors
is dependent on androgens. Hence, in patients with
hypogonadism management with PDE-5 inhibitors may not
be effective and use of androgens may be an effective choice.
Adverse effects of PDE-5 inhibitors are generally mild and
dropout rates due to side effects are similar to placebo.
PDE-5 inhibitors are metabolized by the cytochrome P450
3A4 and as a result may affect metabolism of protease
inhibitors and antifungal medications. In general PDE-5
inhibitors have been shown to be safe and have not been
associated with increased risk of myocardial infarction.
However, it is important to remember that use of PDE-5
inhibitors is contraindicated in those receiving nitrate. Use
of PDE-5 inhibitors along with antihypertensive medication
like ACE inhibitors, angiotensin-receptor blockers, calcium
channel blockers and diuretics can result in small additive
decreases in blood pressure. Use of PDE-5 inhibitors along
with alpha blockers can result in orthostatic hypotension.
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There are no comparative trials to suggest superiority of
one PDE-5 inhibitor over the other. However, preliminary
data from some of the cross-over trials suggest that some
patients may respond better to one PDE-5 inhibitor than
to another. Accordingly, it can be said that a patient who
does not respond to one agent, may be shifted to another
PDE-5 inhibitor. Some preliminary data also suggest that a
proportion of patients who fail to respond to intermittent
dosing, may respond to daily dosing.
The selection of medication is to be done on the basis
of frequency of intercourse. Although very robust data is
not available, but daily use of tadalafil is associated with
improved endothelial function with a sustained effect after
its discontinuation, whereas such effects are not seen with
use of on-demand tadalafil.
Table 16: Home work assignments for Single Male with
Premature Ejaculation
Don’ts to be followed during the initial sessions
• Abstain from heterosexual intercourse and not to experiment during
these sessions
Home work Assignment/Procedural aspects
• Read erotic material, or see erotic material in books/movies, to visualize
it and note the sense of derived sexual pleasure with subsequent erection
of penis
• Imagine himself in the same situation
• In subsequent sessions, combine reading/seeing with gentle touching
of the penis or the testicles/groin region to enhance pleasure, but he
shouldn’t stroke the penis or indulge in masturbation
• Once, the previous step is mastered, patient is asked to combine the
imagery with fondling of penis so as to build up sexual pleasure and can
even indulge in masturbation
• While masturbation, when patient has the feeling of imminent
ejaculation, he is to be instructed to immediately stop masturbation and
practice squeeze technique
• At the end of the therapy the patient is instructed to fantasize about
himself indulging in sexual intercourse with the process of ejaculation
A subject who does not respond to 6-8 doses of a PDE-5
inhibitor with sexual stimulation at maximum dose is
considered as non-responder to a PDE-5 inhibitor. However,
it is to be remembered that most often patients fail to
respond due to incorrect use of PDE-5 inhibitors and these
include failure to use adequate sexual stimulation, adequate
dose and failure to wait for the adequate duration for the
action of the medication to start. It is to be remembered
that even though all the 3 PDE-5 inhibitors have onset of
action within 30 minutes of oral ingestion, in most patients a
lag of 60 minutes is required for sildenafil and verdenafil and
2 hours for tadalafil. Based on the half-life of the medication,
the normal window of efficacy of sildenafil and verdenafil is
6-8 hours after ingestion, whereas the window of efficacy
for tadalafil is about 36 hours. Patient prescribed PDE-5
inhibitors are to be adequately psychoeducated with respect
to dose of medication, timing of medication, relationship
of dosing with fatty meal, need for sexual stimulation and
window during which desired effect will be perceived.
Other oral erectogenic agents
Trazodone: One of the earliest drugs used in erectile
dysfunction was trazodone. Trazodone and its active
metabolite have antagonistic effect on 5HT2C receptors and
may also have adrenoceptor antagonistic action. Available
data suggest that trazodone is more efficacious than
placebo in mixed and psychogenic erectile dysfunction.
Yohimbine: It is a α2-adrenergic blocker. Before introduction
of sildenafil, yohimbine was the most widely used oral
medication for management of erectile dysfunction. Available
evidence suggests that it is more efficacious than placebo.
Apomorphine: Apomorphine is a dopamine agonist (D1 & D2
receptors) and its sublingual form (Apo-SL) is a new central
initiator of erection and has been found to be effective in
various types of erectile dysfunction.. Recent studies show

Table 17: Differentiating features between psychogenic and organic erectile dysfunction

Parameters Psychogenic Organic
Onset of disorder Situational with defined onset (onset Insidious
associated with specific emotional event)
Precipitating event Psychogenic condition Debilitating disease, vascular insufficiency or CNS
abnormality, penile trauma or interfering drugs
Erectile function before intromission May be present Usually absent except in patients with pelvic steal phenomenon
Erectile function after intromission Variable with different partners Usually absent
Erectile response to other sexual stimuli Usually present Usually absent
Nocturnal or morning erections Initially present and full, lost in longstanding Absent or reduced in frequency and intensity
dysfunction
Course of disorder Episodic or transient loss of erection Persistent and progressive erectile
Dysfunction
Associated ejaculatory disorder Premature ejaculation and intermittent loss of Retrograde or absent ejaculation
ejaculation
Nocturnal penile tumescence > 90‑180 min/night <60 min/night
Total time 0.2 cm 2 cm
Circumferential change >0.70 <0.60
Penile‑brachial index (PBI) <35 sec >40 sec
Bulbocavernosus reflex latency

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Avasthi, et al.: Sexual dysfunction
Table 18: Treatment options for erectile dysfunction
Oral Agents
• Sildenafil
• Tadalafil
• Vardenafil
• Trazodone
• Yohimbine
• Apomorphine
• Phentolamine
• L‑arginine
• Androgens (Testosterone)
Vasoactive Intracavernosal Injections (ICI)
• Phenotolamine mesylate
• Papavarine
• Vasoactive intestinal peptide (VIP)
• Forskolin
• Alprostadil
Intraurethral therapy
• Alprostadil
Transdermal therapy
• Testosterone
• Nitroglycerine
• Minoxidol
Vacuum constriction devices (VCD)
Penile Prosthesis
Reconstructive surgeries
that sublingual apomorphine has a safe cardiovascular
profile and thus making it a new treatment option for
patients with concomitant disease including cardiovascular
disease and diabetes mellitus.
Phentolamine: Oral phentolamine mesylate, is a competitive
inhibitor of α- adrenergic receptor. It also has the advantage
of lack of interaction with nitrates and hence has been
suggested as an alternative to treatment of erectile
dysfunction in patients with cardiac illness.
L-arginine: L-arginine is the precursor of Nitric Oxide (NO)
and has been shown to improve erections in 40% of patients.
Androgens
Androgens are useful for erectile dysfunction in men with
severe hypogonadism and may be useful as adjunctive therapy
when other treatments are unsuccessful by themselves. Libido
and an overall sense of well-being are likely to improve when
serum testosterone levels are restored to the reference range.
Some evidence suggests that combination of testosterone and
PDE-5 inhibitors yields better results. Usually testosterone
is used parenterally, either once a week or once in 2
weeks. Other methods of administration like skin patches,
testosterone gel is also available, but this is to be used daily
and is costly. Testosterone implants are also available, which
can last for 3-6 months. However, it is to be remembered that
use of exogenous androgens suppresses natural androgen
production. Elevated serum androgen has the potential to
stimulate growth of prostate gland and increase the risk of
cancer. Use of exogenous testosterone is also known to be
associated with erythrocytosis, elevated serum transaminase
Indian J Psychiatry 59 (Supplement 1), January 2017
levels, exacerbation of untreated sleep apnea, benign prostatic
hyperplasia, and an increased risk of adenocarcinoma of the
prostate. Accordingly, periodic examination of prostate,
estimation of prostate-specific antigen (PSA) and heamogram
are recommended in all patients receiving supplemental
androgens. Obtaining a testosterone level during therapy is
necessary for optimizing the dosage.
Vasoactive Intracavernosal Injections (ICI)
Since early1980s, till advent of sildenafil, intracavernous
injections were the mainstays of the treatment of erectile
dysfunction. The agents which have been used for
intracavernous injections include phentolamine mesylate,
papavarine, vasoactive intestinal peptide (VIP), forskolin
and alprostadil.
Phentolamine mesylate, an a - adrenoceptor antagonist
acts via increasing cAMP and decreasing intracellular Ca2+
and also possibly via nitric oxide synthase (NOS) activation.
Clinical efficacy and safety of intracavernosal mesylate has
been well documented.
Papavarine is a non-selective inhibitor of phosphodiesterase
(PDE) and acts by increasing cAMP thus decreasing
intracellular smooth muscle. It is used in papavarine (20-
80 mg) induced penile erection (PIPE) test to distinguish
between psychogenic and organic ED. However, it has
limited efficacy so it is used with other agents such as
phentolamine and with phentolamine and prostaglandin E1.
VIP and Forskolin which increase cAMP, have been found
to be efficacious in moderate to severe erectile dysfunction
resistant to monotherapy and polypharmacotherapy. No
pain at site of injection has been reported with VIP, which
is an advantage to patients.
Alprostadil, a synthetic prostaglandin E1 is an adenylate
cyclase activator and is now the drug of choice of intra-
cavernosal pharmacotherapy. Intracavernous alprostadil in
the dose of 5-40 μg is most efficacious as monotherapy. It
leads to erection in 5-15 minutes and the duration of ejection
depends on the dose of the medication used. It is reported
have an efficacy of more than 70% and has also been found to
be effective in patients with erectile dysfunction associated
with diabetes mellitus and cardiovascular disease. Patient
and partners also report high satisfaction rates. However,
in long run use of intra-cavernosal alprostadil is associated
with high dropout rates (41-68%), with most dropouts’
occuring during initial 3 months of therapy.
When used it is to be initially be given in the clinicians
office at the lowest dose and gradually the dose need to be
titrated to an adequate erectile response while monitoring
for syncope. Intracavernosal alprostadil is considered to be
more effective and better tolerated over the intraurethral
form. Due to this Intracavernosal alprostadil is preferred
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Table 19: Comparison of various PDE‑5 inhibitors

Sildenafil Vardenafil Tadalafil
Time to maximum plasma 30-120 (median 60) 30-120 (median 60) 30–360 (median 120)
concentration (T max) in minutes
Half‑life in hours 2.6 to 3.7 3.9 17.5
Plasma protein binding 96% 94% 94%
Bioavailability 41% 15% Not known
Onset of action in minutes 15‑60 25 16‑45
Duration of action1 4 4 36
Absorption Fatty meals cause a mean delay in Cmax of Fatty meals cause a Not affected by food
60 minutes reduction in CMAX
Available doses in mg 25, 50, 100 2.5, 5, 10,20 2.5, 5, 10,20
Recommended starting does in 50 10 10
mg/day
Maximum Dose in mg/day 100 20 20
Dose adjustments required • Patients >65 years old • Patients >65 years old • Patients >65 years old
• Hepatic impairment • Hepatic impairment • Hepatic impairment
• Renal impairment • Renal impairment • Renal impairment
• Concomitant use of potent cytochrome P450 3A4 •C oncomitant use of • Concomitant use of
inhibitors, such as ketoconazole, itraconazole, potent cytochrome potent cytochrome
erythromycin, clarithromycin, HIV protease P450 3A4 inhibitors, P450 3A4 inhibitors,
inhibitors (ritonavir and saquinavir) such as ketoconazole, such as ketoconazole,
• Concomitant use of rifampicin, phenobarbital, itraconazole, erythromycin, itraconazole, erythromycin,
phenytoin and carbamazepine, may induce CYP3A4 clarithromycin, HIV clarithromycin, HIV protease
and enhance the breakdown Concomitant use of protease inhibitors (ritonavir inhibitors (ritonavir and
cimetidine and saquinavir) saquinavir)
• Concomitant use of • Concomitant use of rifampicin,
rifampicin, phenobarbital, phenobarbital, phenytoin and
phenytoin and carbamazepine, may induce
carbamazepine, may induce CYP3A4 and enhance the
CYP3A4 and enhance the breakdown
breakdown
Contraindication Patients receiving organic nitrates either regularly or • Patients receiving organic • Any patient using organic
intermittently nitrates either regularly or nitrates either regularly or
Hypersensitivity to any component of the tablet intermittently intermittently
• Hypersensitivity to any • Hyper‑sensitivity to any
component of the tablet component of the tablet
Side effects Headache Headache Headache
Flushing Flushing Dyspepsia
Dyspepsia Rhinitis Back pain
Nasal congestion Dyspepsia Myalgia
Alteration in colour vision Sinusitis Nasal congestion
Recommended time between 1 hour 1 hour 1 to 12 hours
medication intake and intercourse

over intraurethral alprostadil. Common side effects of
intra-cavernosal alprostadil are penile pain, edema and
hematoma, palpable nodules or plaques, and priapism.
Patients are to be clearly informed about the chances of
occurrence of priapism and what do in such situation. The
patient is to be counseled that if the erections persists for
more than 4 hours, they need to seek emergency medical
help. Management of priapism in such situations involves
aspiration of blood from corpus cavernosum under local
anaesthesia. If this fails than intra-cavernosal phenylephrine
injection is to be given with proper monitoring for severe
hypertension, tachycardia and any arrhythmia.
Due to its synergistic action, it is often used with
phentolamine and papavarine. Some studies have
demonstrated that patients of erectile dysfunction preferred
combination [Phentolamine (0.25-1.5 mg) + Papavarine
(8-16 mg) + Prostaglandin E1 (10-20 μg)] to sildenafil,
regardless of the etiology.
A meta-analysis of 25,000 patients showed that the
advantage of mixing above agents is that lower doses of
drugs are required thus leading onto synergistic effects with
lesser side effect. Prominent side effects are pain, priapism,
corporal fibrosis and scar tissue formation. Also, being an
invasive procedure, many patients find it inconvenient to
inject repeatedly. Procedural complicacy, bleeding and
injury to urethra caused higher attrition rates at 1 year
follow-up of patients being treated with intracavernous
vasoactive drugs.
Intraurethral therapy
Medicated urethral system for erection (MUSE), which
contains 500-1000 mg of alprostadil, has shown success

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Avasthi, et al.: Sexual dysfunction
rates varying from 43-69% in efficacy studies. It has
advantages that it can be self-administered and has little
systemic and local side effects.
Topical therapy (Transdermal delivery)
This option minimizes both systemic exposure and tissue
traumatization and involves administration of vasoactive
substances across skin of the penis. This has added benefit
from the patient’s perspective in being a less invasive
option. Pilot studies using Soft Enhanced Percutaneous
Absorption (SEPA) technology, give ground for optimism.
Preliminary evidence suggests that prostaglandin-E1+
SEPA are effective in 80-90% of patients. Nevertheless, this
option requires more intensive research before approval by
regulatory authorities.
Testosterone therapy for ED is indicated only in confirmed
cases of endocrinopathies and is to be reserved for
patients with documented hypogonadism. Transdermal
administration has been developed recently. Gel containing
2.5-5.0 mg of testosterone-applied daily to the abdomen,
back, thighs or upper arms have shown to produce normal
plasma testosterone levels. Patients using testosterone
skin patches have reported improvements in libido, sexual
function, energy and mood. Adverse skin reaction (9% of cases)
can be treated with topical hydrocortisone or antihistamine
cream. Serum prostate specific antigen (PSA) levels is to be
measured before testosterone therapy is started.
Nitroglycerine, a nitric oxide donor and minoxidil ointments
have met with only minimal success. Although still under
investigation, but these agents could acts as another tool in
the armamentarium for treating erectile dysfunction.
Vacuum constriction devices (VCD)
Vacuum devices work by exerting a negative pressure on
the penis, which results in an increase in corporeal blood
flow and erection. A constriction ring placed around the
base of the penis prolongs the erection by decreasing
corporeal drainage. The erection obtained with a vacuum
device is different from that obtained normally as there
is no relaxation of the trabecular smooth muscle. Instead
blood is trapped in the intra and extracorporeal regions
of the penis. The time taken to achieve an erection varies,
but is generally around 2-2.5 mins. The band need not be
left in the place for more than 20 mins. Majority of the
vacuum devices currently marketed use either a battery or
a hand pump to generate vacuum. Overall success rate with
VCD has been reported to be around 90%, with more than
80% of patients continuing with the device. Another study
quoted that 53% patients reported satisfaction with only
23% continuing with the device. Drawbacks of VCDs include
pain, petechiae, obstruction of ejaculation, penile pivoting,
numbness and slight bluish colouration due to cyanosis.
Almost all patients of ED can use VCDs. The vacuum devices
are contraindicated in patients with severe Peyronie’s
Indian J Psychiatry 59 (Supplement 1), January 2017
curvature, sickle cell anaemia or blood dyscrasias and those
on anticoagulants.
Penile Prosthesis
Since their introduction about 3 decades ago, penile
implants are still a widely chosen treatment option, mostly
after failure of all forms of therapy for erectile dysfunction.
There are various forms of penile prosthesis, i.e., semi-rigid
rod prosthesis consists of two rod like cylinders that are
implanted into corpora cavernosum, mechanical rods (Dura
II), malleable rods and inflatable penile prosthesis (Unitary,
two-piece, and three-piece devices). Usually 3 piece
inflatable penile prosthesis is preferred as it leads to more
natural erections. Postoperative complications of penile
implants include infection and mechanical malfunction.
Peri-prosthetic infection requires immediate antibiotic
therapy and removal of prosthesis.
Reconstructive surgery
Surgery for venous leakage involves penile venous ligation
or embolization. Venous ligation restores spontaneous
erections in only 50% of patients. Arterial revascularization
is an experimental procedure used for treatment of
vasculogenic ED. Upto 65% of patients report return of erectile
function following arterial revascularization, but careful
patient selection is necessary. Generally, good results are
obtained only in young men with pure arteriogenic erectile
dysfunction. A number of complications associated with
arterial revascularization including arterial haemorrhage,
glans-penis hyperemia, anastomotic occlusion, diminished
penile sensation and fibrosis.
Steps in the Management of Erectile Dysfunction
First step is to confirm the diagnosis of erectile dysfunction
as per the prevailing nosological system. The consensus is
that inability to attain and maintain an erection sufficient
to permit satisfactory sexual performance, lasting for more
than 6 months, is considered to be an indicator of presence
of erectile dysfunction. The general principles of evaluation
of erectile dysfunction are shown in Table-20. The most
important issue in management is evaluation for the organic
factors, look for comorbid psychiatric conditions, comorbid
sexual dysfunction and marital disharmony. However, it is
to be remembered that although the cause may be organic,
psychological causes can worsen the ED, so treating with
behavioural measures in such cases is also an important
step in the management. Once the evaluation is complete
the patient/couple is to be explained about the potential
beneficial and adverse effects of available treatment and
guide them to make an informed choice. The selection of
treatment strategy for erectile dysfunction is outlined in
figure-3. If patient has Dhat syndrome along with erectile
dysfunction, it is to be addressed first. Psychiatric disorders
and marital harmony is to be addressed prior to treatment
of erectile dysfunction and a similar protocol need to be
followed.
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Avasthi, et al.: Sexual dysfunction

Initial treatment involves providing sex education,
clarifying the myths, teaching relaxation exercises,
and sensate focus training. After assessing coexistent
problems, while providing formulation and sex education,
education about factors that create a normal sexual
response and erectile dysfunction can help patients
and their partners cope with sexual difficulties. It is
also important to change/remove/reduce the associated
modifiable or reversible factors, including lifestyle or
drug-related factors. Changes in lifestyle like smoking
cessation, control of diabetes/ cholesterol, weight loss and
reduction in stress are of prime importance. The success
of psychosexual therapy is guided by the motivation of
the patient, as this require him to work with the therapist
to understand what prevents him from experiencing
normal sexual arousal.
Follow-up plan is to be tailor made for the individual and
there is no single follow-up regime. However, regular
follow-up at 4 weeks for 6 months is usually recommended.
In terms of pharmacological treatments (see Table-21),
PDE-5 inhibitors are considered to be the first line therapy
in treatment of erectile dysfunction. The PDE-5 inhibitors
available in India include sildenafil, vardenafil and tadalafil.
Apomorphine sublingual has the advantage of quick onset
Table 20: General principles of evaluation of erectile
dysfunction
• Establish diagnosis based on the history, physical examination and
investigations as per requirement
• Establish the cause of erectile dysfunction (psychogenic, organic, mixed)
based on the history, physical examination and investigations as per
requirement
• Use validated questionnaires like International Index of Erectile
Function (IIEF) for grading the severity so as to monitor the response to
specific treatment
• Evaluate for presence of comorbid psychiatric disorders and establish the
relationship with erectile dysfunction (i.e., what is primary psychiatric
disorder or erectile dysfunction)
• Evaluate the severity of underlying organic cause and treat the primary
illness first

Treat Dhat Identification of Erectile Dysfunction Liaison with

syndrome & • Sexual, Medical, Psychosocial history specialist for
Marital Discord • Assessment of relationship with partner organicity
prior to (both sexual & non-sexual)
management of • Physical Examination
ED • Evaluate for Psychiatric comorbidity
• Evaluate for other sexual dysfunctions

Psychiatric comorbidity
present/ severe
Functional
erectile
dysfunction
Treat appropriately
and then focus on ED

First line therapy

• Sex Education, Relaxation, Sex therapy, Life style modification
• Oral erectogenic agents (PDE5 inhibitors)

• Evaluate for the reasons for lack of response- improper use of PDE-5
inhibitors, poor compliance with medication, missed physical comorbidities,
missed hypogonadism

Retrial with PDE-5 inhibitors

• Proper education about how to use PDE-5 inhibitors Erectile
• Change from intermittent use to daily use Dysfunction
• Combine with testosterone in case of presence of hypogonadism resolved

Second Line therapy:

• Change Oral Erectogenic Agent Reevaluate for
• Intracavernosal self injection Organic cause
• Intraurethral alprostadil
• Combine PDE-5 inhibitors with
second line agents

Figure-3: Treatment algorithm for management of patients with ED

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Avasthi, et al.: Sexual dysfunction
of action. It is well tolerated and there is no interactive
action with other medications, food and alcohol. This can
be prescribed by physicians to patients with psychogenic
and a mild organic impotence. It is also used when PDE-5
inhibitors are contraindicated. VCDs are better accepted by
older patients especially who have a stable partner. Penile
pain, numbness and delayed ejaculation are some of the
side effects that treating psychiatrist need to be aware of.
Psychosexual therapy is also the first line treatment and it
is used in patients with significant psychological problems,
though psychological component may be present in all
cases of erectile dysfunction. It is used either alone or in
combination with other first line therapies. The motivation
of the patient is of utmost importance for any psychosexual
therapy. The major advantages are that it is non-invasive,
involves the partner, and leads to sustainable improvement
in sexual function and satisfaction. However, it takes time,
is associated with high dropout rates and is associated with
variable results.
If the first line therapies fail or are contraindicated than the
second line treatment includes use of intracavernosal and
intraurethral injections. Patient’s comfort and education is
very important while using intracavernosal and intraurethral
injections. Use of an automatic special pen that avoids
the needle view can avoid fear of penile puncture. It is
helpful in most cases of erectile dysfunction; however, it
is contraindicated in patients with hypersensitivity to drug
employed and priapism. Erection appears within 5-15 mins.
The psychiatrist is to be aware of the side effects like
priapism, penile pain and fibrosis. In cases where the penile
erection lasts more than 4 mins aspiration of blood by a
19 gauge needle has been suggested. If it still does not
resolve then 200mg of Phenylepherine intracavernosal
injections every 5 mins is recommended. Intraurethral PGE1
as semisolid pellets is a less invasive procedure but success
rates are lower. In case both first and second line therapies
fail, use of inflatable penile prosthesis can be considered.
Premature Ejaculation (PME)
Specific Non Pharmacological for specific sexual dysfunctions
It is considered that behavioural management is to be
the first line of therapy where ever possible. The specific
behavioural techniques for PME involves stop- start or
squeeze techniques, which are usually introduced during
genital sensate focus.
Table 21: Management of Erectile dysfunction
First line therapy: Phospho‑diesterase‑5‑inhibitors, apomorphine, vacuum
constriction devices and psychosexual therapy
Second ‑ line therapy ‑ intracavernosal and intraurethral injections:
prostaglandin E1, phentolamine, vasoactive intestinal peptide and
papavarine.
Third line therapy: penile prosthesis. The inflatable type is cosmetically
better but prosthesis infection is most problematic complication.
Indian J Psychiatry 59 (Supplement 1), January 2017
The stop-start technique developed by Masters and Johnson
is highly effective for the treatment of premature ejaculation
with success rates of as high as 90%. The technique aims
to increase the frequency of sexual contact and sensory
threshold of the penis. It is best carried out in the context
of sensate focus exercises because some males ejaculate
so early that direct stimulation of the penis of any kind
can trigger ejaculation straight away. Starting with non-
genital caresses allows the male more time to identify the
sensations that occur immediately prior to ejaculation. The
stop-start technique consists of the man lying on his back and
focusing his attention fully on the sensation provided by
the partner’s stimulation of his penis. When he feels himself
becoming highly aroused he is to indicate this to her in pre-
arranged manner at which point she need to stop caressing
and allow his arousal to subside. After a short delay this
procedure is repeated twice more, following which the
woman stimulates her partner to ejaculation. At first the
man may find himself ejaculating too early, but usually
gradually develops control. Later a lotion can be applied to
the man’s penis during this procedure, which will increase
his arousal and make genital stimulation more like vaginal
containment.
The squeeze technique is an elaboration of the stop-start
technique, and probably only needs to be used if the latter
proves ineffective. The couple proceeds as with the stop-
start procedure. When the man indicates he is becoming
highly aroused his partner should apply a firm squeeze
to his penis for about 15-20 seconds. During applying the
pressure, the forefinger and middle finger are placed over
the base of the glans and shaft of the penis, on the upper
surface of the penis, with the thumb placed at the base of
the undersurface of the glans. This inhibits the ejaculatory
reflex. As with the stop-start technique this is repeated
three times in a session and on the fourth occasion the man
may ejaculate.
Both procedures appear to help a man develop more control
over ejaculation, perhaps because he gradually acquires the
cognitive techniques associated with ejaculatory control,
or perhaps because he gradually becomes accustomed
to experiencing sexual arousal without getting anxious
(Hawton, 1989). Stop-Start technique and Squeeze technique
have been documented to have anywhere between 60-95%
success rates.
Pharmacological management of Premature Ejaculation
(PME)
Pharmacological treatment of premature ejaculation includes
use of topical anesthetic agent, tricyclic antidepressants and
selective serotonin reuptake inhibitors (SSRIs) (Table-22).
There is preliminary data for use of sildenafil and some of
the Chinese herbs. However, it is important to note that
none of these agents have been approved.
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Over the last few years, dapoxetine, another non-selective
SSRI, has been marketed specifically for management of PME.
Dapoxetine has been found to be efficacious in both lifelong
and acquired PME. Dapoxetine is associated with side effects
like nausea, diarrhoea, headache and dizziness. Combining
dapoxetine with PDE-5 inhibitors is associated with increased
risk of syncope. It is generally recommended that patient’s
blood pressure is to be evaluated prior to starting of dapoxetine.
Among the SSRIs, paroxetine has been found to be useful.
However, data also exist for the beneficial effect of sertraline.
Studies which have compared various SSRIs suggest that
paroxetine is superior to fluoxetine, clomipramine and
sertraline. Data also suggest that sertraline is better than
fluoxetine; however, the efficacy of clomipramine is not
significantly different from fluoxetine and sertraline.
Chinese herbs like S-S cream, which are used as topical agents,
have claimed good efficacy and favorable side effect profile.
PDE-5 inhibitors have also been evaluated for management
of PME. Some of the available data suggests that using
combination of SSRIs and PDE-5 inhibitors leads to better
outcome than use of SSRIs alone.
SSRIs can be used on continuous basis or on situation basis,
i.e. pre-intercourse. It is unclear as which of the two is
more effective. There is no clear consensus as to whether
SSRIs will effect an eventual cure of PME allowing for
discontinuation of the medication, or whether SSRIs will be
required for life. The general consensus is that PME usually
returns upon discontinuation of therapy.
Steps in management of Premature Ejaculation (PME)
Firstly, the diagnosis of premature ejaculation be made as
per the prevalent nosological system. The working diagnosis
of PME is made if ejaculation occurs sooner than desired
either before or soon after penetration causing distress to
either or both partner for more than 3 months. The general
principles of management are shown in Table-23.
The general guideline for selection of mode of treatment
is given in figure-4. The first step for treatment involves
evaluation for presence of comorbid sexual dysfunctions,
comorbid psychiatric disorders and marital discord. If
patient has erectile dysfunction or Dhat syndrome along
with PME, these is to be addressed first. If patient has a
psychiatric disorder it needs to be carefully evaluated – is it
primary or secondary to sexual dysfunction, and how severe
it is. If the psychiatric comorbidity is primary and/or severe,
it is to be addressed first. Sometimes the PME is secondary
to the poor interpersonal relationship between the couple,
so it needs to be addressed prior to treatment of PME.
Initial treatment involves providing sex education, clarifying
the myths, relaxation and correction of situational factors (if
S110
Table 22: Treatment options for premature ejaculation
Antidepressants Recommended dose
Non selective 25‑50 mg/day or 25 mg 4‑24 hours prior to intercourse
Serotonin
reuptake inhibitor
‑ Clomipramine
SSRI ‑ Fluoxetine 5‑20 mg/d ay
SSRI ‑ Paroxetine 10‑40 mg/day or 20 mg, 3‑4 hours prior to intercourse
SSRI ‑ Sertraline 25 to 200 mg or 50 mg 4‑8 hrs prior to intercourse
SSRI ‑Dapoxetine 30 mg and 60 mg, on demand use, 1‑2 hours before
intercourse
Tramadol 62 mg of tramadol oral dispersible tablets, and 89 mg
of tramadol oral dispersible tablets, used on demand
Topical therapies Dose
Lidocaine/ Lidocaine 2.5‑5%, 20‑30 mins. prior to intercourse
prilocaine cream
Table 23: General principles of evaluation of premature
ejaculation
• Establish diagnosis based on the history given by patient and the partner
• Proper physical examination of genitalia and secondary sexual characters
is necessary
• Evaluate the general relationship issues and marital discord between the
couple
• Look for comorbid sexual dysfunction, psychiatric morbidity and physical
illnesses
• Evaluate relationship with comorbid psychiatric disorders (i.e., what is
primary ‑ psychiatric disorder or premature ejaculation)
• Evaluate the severity of underlying organic cause and treat the primary
illness first
present) contributing/causing the dysfunction and following
the sensate focus training. It is considered that behavioural
management is the first line of therapy wherever possible.
But some authors suggest that men with lifelong premature
ejaculation need to be managed with a combination of
pharmacotherapy and behavioural management, while
those with acquired or situational PME can be treated with
pharmacotherapy and/or behavioral therapy according
to patient/partner preference. The specific behavioural
techniques for PME involves stop- start or squeeze techniques,
which are usually introduced during genital sensate focus. The
pharmacotherapy involves use of Dapoxetine, SSRIs, TCAs,
Buspirone and topical agents. If either of the therapeutic
measure fails then a combination of both may be tried.
Combination of SSRIs and PDE-5 inhibitors has also been
reported to lead to better outcome than use of SSRIs alone.
Selection of specific treatment modality is to be made based on
physician judgment and patient’s informed choice. The primary
outcome measure is to be the patient’s and partner satisfaction.
Risk and benefits of all treatment options are to be discussed
with patient prior to any intervention.
Dhat syndrome
The first step in the management of Dhat syndrome
involves evaluation for comorbid sexual dysfunctions,
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Avasthi, et al.: Sexual dysfunction

psychiatric disorders and presence of possible urinary
tract infection (UTI) and sexually transmitted diseases
(STD). Where ever there is a suspicion, local examination,
appropriate investigations for infective pathology and
phosphaturia need to be done and adequate treatment
is to be provided. Even after appropriate treatment, if
the symptoms persist then the subject is to be provided
adequate sexual knowledge.
Diagnosis is based
on sexual history
Evaluate for other sexual
dysfunctions
• ED
• Dhat syndrome
Whenever patient has comorbid Dhat syndrome along with
PME or ED, Dhat syndrome is to be treated first. If the
psychiatric comorbidity is primary and/or severe, it need to
be addressed first (See figure-5).
The most important aspect of treatment of Dhat syndrome is
providing adequate sex knowledge and clarifying sexual myths.
Sex education mainly focuses on anatomy and physiology
of sexual organs and their functioning with reference to
masturbation, semen formation, nocturnal emissions and
their functioning with genitourinary system independent of
gastro-intestinal tract etc. If there is the presence of associated
anxiety or depressive symptoms that impede the process of
Treat ED, Dhat therapy, anxiolytics or/and antidepressants can be added for
syndrome first
the least possible time and in the least possible doses.

Impaired sexual interest in men or women:

• Look for the presence of couple Treat marital
Treat psychiatric
morbidity if disharmony, depression, disharmony before Besides the general measures, no particular procedures are
prominent and anxiety, situational factors behavioural
management
used in the treatment of this problem. The main emphasis
severe
is on setting the right circumstances for sexual activity,
reducing anxiety, establishing satisfactory fore play, focusing
Discuss treatment options with patient and partner
attention on erotic stimuli and cognitions and resolving
Discuss the efficacy of each treatment options the general issues of relationship between the couple. It is
generally agreed that desire disorders have a substantially
PHARMACOLOGICAL poorer response to psychotherapy (<50%) than other forms
Topical anesthetic
Oral medications
NON-PHARMACOLOGICAL
Reassurance, Sexual education
of sexual dysfunction (≥ 70%). In addition, therapy tends
Antidepressants –Dapoxetine, SSRIs, TCA Relaxation to be more difficult and the conventional sex therapy
Buspirone, combination of SSRIs+PDE-5 Sensate focus
inhibitors Stop and start technique techniques (e.g., sensate focus) are generally inadequate.
Oral medications +Topical anaesthetic Squeeze technique
Hence, a more flexible and person centric approach to
treatment is required. Many authors have tried approaches
like cognitive-behavioral therapy, systems approach, script
Combination of Pharmacological & Non-Pharmacological treatment
modification, clinical hypnosis, guided fantasy exercises,
Figure 4: Guidelines for Premature ejaculation and sexual assertiveness training. Cognitive-behavioral

Dhat Syndrome

Treat with
appropriate
Pharmacotherapy,
Evaluate for comorbid sexual somatic treatment
Investigate & dysfunction and psychotherapy
Treat appropriately Evaluate for comorbid
in liaison with Psychiatric disorders
specialist Evaluate for possible UTI and
STD

Treat Dhat syndrome before ED / PME

Assess for sex knowledge & clarify the misconceptions
and myths
Provide knowledge about semen formation & nocturnal
emissions
Relaxation technique

Treat other sexual dysfunctions if present

Figure 5: Treatment Algorithm of Dhat syndrome

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Avasthi, et al.: Sexual dysfunction

therapy emphasizes the role of thoughts and beliefs in
perpetuating the maladaptive behavior and is useful
when beliefs held by the patient or couple about norms
or responses is contributing to the sexual problem. The
“systems” approach, targets dynamics between the couple
and allows assessing the extent to which sexual dysfunction
is used by the couple to maintain a “sexual equilibrium”
within the relationship (i.e., the way sexual dysfunction is
used to regulate intimacy or to allow the share of blame
between partners for the failure of the relationship).
Steps in the management of impaired sexual interest in
men or women:
The most important issue in management is evaluation for
the organic factors, evaluation for presence of comorbid
psychiatric conditions, comorbid sexual dysfunction
and marital disharmony. But it is to be remembered that
although the cause may be organic, psychological causes
can decrease the sexual interest, these also need to be
focused adequately. Many couples have marital disharmony
associated with decrease sexual interest and treating the
same would be the only thing which is required.
Besides the general measures, no particular procedures
are used in the treatment of this problem. The main
emphasis is on setting the right circumstances for sexual
activity, reducing anxiety, establishing satisfactory fore
play, focusing attention on erotic stimuli and cognitions
and resolving the general issues of relationship between
the couple. More flexible and individualistic approach to
treatment is required. The general outline of management
is shown in figure-6.
Female sexual Dysfunction
Formulation of a treatment plan
Firstly female sexual disorders need to be diagnosed as per
the current definitions. Initial treatment planning requires a
thorough assessment of the patient, with the goals of support,
normalization, permission giving, sex education, stress
reduction, symptom alleviation, improve communication skills
(sexual & others) and attitude change. The thorough assessment
includes a comprehensive medical and psychological history of
the patient and her partner. Like in male sexual dysfunction,
psychiatrist treating female sexual dysfunction is to be aware
of the etiology including genitourinary, endocrinological,
vascular and neurological systems. The general principles of
assessment of female patients with sexual dysfunction are
given in Table-24. A multidisciplinary approach is of paramount
importance in female sexual dysfunction.
Vaginismus
It is important to remember that many women who present
with vaginismus have negative attitude towards sex and
quite a few are victim of sexual assault. Some may also
have the belief that premarital sex is wrong or sinful. This
belief may be so ingrained that, even when intercourse is
sanctioned by marriage, it may be difficult to relax physically
or mentally during sexual intercourse. Some times the cause
of vaginismus may be a fear that is instilled by friends or
family by suggesting that the first experience of intercourse
is likely to be painful or bloody. Another important cause of
vaginismus is fear of pregnancy.
The sex education needs to focus on clarifying normal
sexuality and reducing negative attitude for sex. Besides

Hypoactive sexual desire

Investigate & Treat Treat with

appropriately in appropriate
liaison with specialist Pharmacotherapy,
Evaluate for comorbid somatic treatment and
Psychiatric disorders psychotherapy
Evaluate for Marital problems
Look for organic causes
Treat general
marital issues prior
to sex therapy

Psychological management
• General behavioural management- relaxation, sex
education, clarification of myths, sensate focus
• Individual therapy
Pharmacological
• Apormorphine (Sublingual) , Bupropion
• Hormonal Treatment - estrogen, testosterone
• Sildenafil

Treat other sexual dysfunctions if present

Figure 6: Treatment Algorithm of Hypoactive sexual desire

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Avasthi, et al.: Sexual dysfunction
Table 24: General principles of evaluation of female
sexual dysfunction
• Assessment of predisposing, precipitating and maintaining factors
• Evaluation of sexual relationship with partner
• Comprehensive medical and psychosexual history
• Assessment for sexual abuse, recurrent depression, substance abuse,
self‑harm and promiscuity
• Focused pelvic examination for pelvic trauma and PAP smear need to be
done in all cases of sexual dysfunction.
the use of general relaxation exercises, the relaxation
procedure also needs to focus on teaching the women to
relax muscles around the inner thigh and pelvic area.
The specific management involves the following stages:
1. Helping the woman develop more positive attitudes
towards her genitals. After fully describing the female
sexual anatomy, the therapist need to encourage
the woman to examine herself with a hand mirror
on several occasions. Extremely negative attitudes
(especially concerning the appearance of the genitals,
or the desirability of examining them) may become
apparent during this stage, possibly leading to failure
to carry out the homework. Some women find it easier
to examine themselves in the presence of the partners;
others may only get started if the therapist helps them
do this first in the clinic. If this is necessary a medically
qualified female therapist is to be involved.
2. Pelvic muscle exercises. These are intended to help the
woman gain some control over the muscles surrounding
the entrance to the vagina. If she is unsure whether or
not she can contract her vaginal muscles she may be
asked to try to stop the flow of urine when she next
goes to the toilet. The woman can later check that she
is using the correct muscles by placing her finger at the
entrance to her vagina where she need to be able to feel
the muscle contractions. Subsequently she is advised to
practice firmly contracting these muscles for an agreed
number of times (e.g. 10) several times a day.
3. Vaginal penetration. Once the woman has become
comfortable with her external genital anatomy she is
advised to explore the inside of her vagina with her
fingers. This is partly to encourage familiarity and partly
to initiate vaginal penetration. Negative attitudes may
also become apparent at this stage (e.g. concerning the
texture of the vagina, its cleanliness, fear of causing
damage, and whether it is ‘right’ to do this sort of
thing). The rationale for any of these objections is
to be explored. At a later stage the woman might try
using two fingers and moving them around. Once she is
comfortable inserting a finger herself, her partner need
to begin to do this under her guidance during their
homework sessions. A lotion (e.g. K-Y or baby lotion)
can make this easier. Graded vaginal dilators can be
used. However, clinical experience has shown that the
use of fingers is just as effective.
Indian J Psychiatry 59 (Supplement 1), January 2017
4. Vaginal containment. When vaginal containment is
attempted the pelvic muscle exercises and the lotion
are used to assist in relaxing the vaginal muscles and
making penetration easier. This is often a difficult
stage and the therapist therefore needs to encourage
the woman to gain confidence from all the progress
made so far. Persisting concerns about possible pain
may need to be explored, including how the woman
might ensure that she retains control during this stage.
5. Movements during containment: Once containment
is well established the couple is asked to introduce
movement during containment, with preferably women
starting the movements first. With this the general
programme of sex therapy is completed and now
the treatment needs to include superimposition of
treatment for specific sexual dysfunctions.
Steps in the management of vaginismus: Treatment is to
be individualized for each woman and/or partner, whenever
possible with their input. Psychological issues as well as
interpersonal issues need to be addressed first. The sex
education needs to focus on clarifying normal sexuality
and reducing negative attitude for sex. Besides the use of
general relaxation exercises, the relaxation procedure needs
to focus on teaching the women to relax muscles around
the inner thigh and pelvic area. The specific behavioural
management is to be followed.
Dyspareunia
Besides the general measures and sensate focus, treatment
of dyspareunia involves sex education. The sex education
need to focus on the importance of adequate arousal and
the couple may also be helped by specific suggestions for
modifying their usual intercourse positions. Couple may be
helped by avoiding positions that lead to deep penetration
(such as vaginal entry from the rear) and by adopting
positions in which the woman is in control of the depth
of penetration (woman on top) or in which penetration is
not too deep (side by side or `spoons’ position). Another
important aspect of treatment of dyspareunia due to
psychological causes is helping the woman become aroused
by teaching the sensate focus programme.
In woman with repeated pain experience on intercourse,
it is likely that they will tense up on future occasions in
anticipation of further pain. Such tension may actually
increase pain as the muscles may be more resistant to
penetration. Due to this, relaxation exercises prior to or
during intercourse may be helpful. Progressive muscle
relaxation prior to sexual activity may allow the women
to reduce the body tension, while more specific relaxation
exercises just prior to intercourse may help to relax the
muscles around the pelvic region and may enhance arousal.
As a woman acquires a number of coping techniques for
minimising the likelihood of pain, positive self-talk may be
helpful. Such self-talk can involve the woman reminding
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Avasthi, et al.: Sexual dysfunction

herself that she is in control of the situation and she will be
the one to determine when penetration is to occur and how
deep penetration will be.
Steps in the management of Dyspareunia: As with most
of the other sexual dysfunctions, the first step is to rule
out other causes/factors that can cause pain. Also the
assessment needs to rule out vaginismus and dryness of
vagina. Treatment of dyspareunia includes sex education
and teaching sensate focus (Figure-7). In particular, it
may be helpful for the couple to avoid deep penetration
positions (such as vaginal entry from the rear) and to assume
positions in which the woman is in control of the depth of
penetration (woman on top) or in which penetration is not
too deep (side by side or `spoons’ position).
is generalized or partner specific needs to be explored.
Although empirically validated non-pharmacological
treatments are not available yet, individual/couples
therapy and medical/ psychological treatment have been
tried in desire disorders in females. In recent times, a
pharmacological agent, flibanserin has been approved for
the management of hypoactive sexual desire disorder in
premenopausal women. The recommended dose0 is 100
mg per day at bed time. Data from metanalysis shows
that compared to placebo, flibanserin is associated with
higher satisfying sexual events per month. Its use is
associated with side effects like dizziness, somnolence,
nausea, and fatigue. If a patient does not show
improvement, the drug needs to be discontinued after
8 weeks.

Arousal disorder Aversion disorders

It is very important to rule out comorbid desire disorders
before treating arousal disorders. If there is comorbid desire
disorder then it needs to be treated first before arousal
disorders are treated. There is no empirically validated
treatment available for arousal disorders due to the fact that
this is a less researched area. Approach usually depends on
the etiology of the arousal disorders. Sensate focusing, CBT,
systematic desensitization, individual and couples therapy,
directed masturbation and communication skills have been
tried in arousal disorders with moderate results.
Sexual abuse or rape, trauma, relationship problem, marital
problem can lead to sexual aversion disorder. Therefore,
all clinicians treating sexual aversion disorders need to
be aware of these causes. In Aversion disorders also no
empirically validated treatment is available however the
clinicians usually employ couple / individual therapy.
Termination of treatment
The termination of the treatment must be planned carefully.
The various strategies and component of termination are:

Desire disorders Prepare for termination from the start of treatment: The
Assessment regarding whether primary or secondary patient/couple should be told about the likely duration of
needs to be settled. Also, whether the desire disorder therapy at the beginning of the treatment. Setting the time

Dyspareunia
• Note: Dyspareunia should only be diagnosed if there is no
other sexual dysfunction such as vaginal dryness or
vaginismus that is causing the pain.

Investigate & • Evaluate for comorbid

treat sexual dysfunction
appropriately in • Evaluate for comorbid
liaison with Psychiatric disorders
Treat with
specialist • Evaluate for possible
appropriate
local pathology - UTI,
Pharmacotherapy,
STD, episiotomy scar,
somatic
endometriosis, ovarian
treatment and
cyst etc.
psychotherapy

Sex education
Provide information about suitable intercourse
positions
Progressive muscle relaxation prior to sexual activity
Positive self-talk
Sensate focus

Figure 7: Treatment Algorithm of Dyspareunia

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Avasthi, et al.: Sexual dysfunction
frame will encourage the patient/couple to work on the
homework assignments.
Towards the end of treatment extend the intervals between
sessions: The intervals between the last two to three sessions
need to be extended to two to three weeks.
Prepare for relapse: The therapist need to prepare the couple
for relapse. About three-fourth of men will experience
recurrence of their problem following treatment. Hence,
treatment also needs to assist men to cope well with
relapse. Most recurrences occur in a temporal pattern (i.e.,
will occur more at certain times than at others) and usually
improve naturally or with self-initiated restart of treatment
techniques. The understanding that relapses are normal
expected helps to reduce the anxiety and sense of failure
that may otherwise prolong erectile difficulties.
Follow-up assessments: Follow-up assignments help the
therapist to evaluate the short-term effectiveness of
treatment.
SUGGESTED READING
1. Abdel Hamid IA, El Naggar EA, ElGilany AH. Assessment of as needed
use of pharmacotherapy and pause-squeeze technique in premature
ejaculation. International Journal of Impotence Research, 2001; 13: 41-45.
2. Abdel Hamid IA. Phosphodiesterase 5 inhibitors in rapid ejaculation:
potential use and possible mechanisms of action. Drugs, 2004; 64: 13-26.
3. Alberta Medical Association. The Guidelines for the Investigation and
Management of Erectile Dysfunction, 2005.
4. American Psychiatric Association. Diagnostic and statistical manual
of mental disorders: DSM-5. Washington, D.C: American Psychiatric
Association, 2013.
5. Anastasiadis AG, Salomon L, Ghafar MA,Burchardt M, Shabsigh R.
Female sexual dysfunction: State of the art. Curr Urol Rep, 2002; 3:
484–91.
6. Asimakopoulos AD, Miano R, Finazzi Agrò E, Vespasiani G, Spera E. Does
current scientific and clinical evidence support the use of phosphodiesterase
type 5 inhibitors for the treatment of premature ejaculation? A systematic
review and meta-analysis. J Sex Med. 2012;9:2404-16.
7. Avasthi A, Gupta N. Manual for standardized Management of Single males
with sexual Disorders. Marital and Psychosexual Clinic, Department of
Psychiatry, PGIMER, Chandigarh, 2002.
8. Avasthi A, Rao TSS, Grover S, Biswas PS, Kumar S. Indian Psychiatric
Society: Clinical Practice Guidelines for management of sexual
dysfunctions. (Eds): Shiv Gautam & Ajit Avasthi. Published by Indian
Psychiatric Society, 2006; Volume II, 144 -231.
9. Avasthi AK, Varma VK, Nehra R, Das K. Construction and standardization
of a sex knowledge and attitude questionnaire (SKAQ) in simple Hindi, for
North Indian population. Indian Journal of Psychiatry, 1992; 34:24-27
10. Bai Y, Pu C, Han P, Li J, Yuan H, Tang Y, Wang X, Wei Q. Selective
Serotonin Reuptake Inhibitors Plus Phosphodiesterase-5 Inhibitors for
Premature Ejaculation: A Systematic Review and Meta-analysis. Urology.
2015;86:758-64.
11. Choi HK, Jung GW, Moon KH, Xin ZC, Choi YD, Lee WH, Rha KH, Choi
YJ, Kim DK. Clinical study of S-S cream in patients with lifelong premature
ejaculation. Urology, 2000;55: 257-261.
12. Cooper K, Martyn-St James M, Kaltenthaler E, Dickinson K, Cantrell A.
Indian J Psychiatry 59 (Supplement 1), January 2017
Interventions to treat premature ejaculation: a systematic review short
report. Health Technol Assess. 2015;19:1-180.
13. Grover S, Avasthi A, Aneja J, Gauri Shankar, Ravi Mohan M, Nehra R,
Padhy S. Comprehensive Questionnaire for assessment of Dhat syndrome:
development and use in patient population. J Sexual Medicine 2014; 11:
2485-95.
14. Grover S, Avasthi A, Gupta S, Dan A, Neogi R, Behere PB, Lakdawala B,
Tripathi A, Chakraborty K, Sinha V, Bhatia MS, Pattojoshi A, Rao TS,
Rozatkar A. Comorbidity in patients with dhat syndrome: a nationwide
multicentric study. J Sex Med. 2015;12:1398-401.
15. Grover S, Avasthi A, Gupta S, Dan A, Neogi R, Behere PB, Lakdawala B,
Tripathi A, Chakraborty K, Sinha V, Bhatia MS, Pattojoshi A, Rao TS,
Rozatkar A. Phenomenology and beliefs of patients with Dhat syndrome:
A Nationwide multicentric study. Int J Soc Psychiatry 2016;62: 57-66.
16. Grover S, Avasthi A, Gupta S, Hazari N, Malhotra N. Do female patients
with nonpathological vaginal discharge need the same evaluation as for
Dhat syndrome in males?. Indian J Psychiatry 2016;58:61-9.
17. Grover S, Kate N, Avasthi A, Rajpal N, Umamaheswari V. Do females
too suffer from Dhat syndrome: a case series and revisit of the concept?
Indian J Psychiatry 2014; 56: 388-392.
18. Hatzichristou D, Rosen RC, Broderick G, Clayton A, Cuzin B, Derogatis L,
Litwin M, Meuleman E, O’Leary M, Quirk F, Sadovsky R, Seftel A. Clinical
evaluation and management strategy for sexual dysfunction in men and
women. Journal of Sexual Medicine, 2004;1:49-57.
19. Hatzichristou DG, Hatzimouratidis K, Bekas M,Apostolidis A, Tzortzis V,
Yannakoyorgos K. The diagnostic steps in the evaluation of patients with
erectile dysfunction. J Urol,2002; 168:615–20.
20. Hatzimouratidis K, Eardley I, Giuliano F, Hatzichristou D, Moncada I,
Salonia A, Vardi Y, Wespes E. Guidelines on Male Sexual Dysfunction:
Erectile dysfunction and premature ejaculation. European Association of
Urology Web site. http://uroweb.org/guideline/male-sexual-dysfunction/.
Updated 2015.
21. Hawton K. Sex therapy: A Practical guide. New York, Oxford University
Press, 1985.
22. Hawton K. Sexual dysfunctions. In: Cognitive Behaviour Therapy for
Psychiatric Problems A Practical Guide ( Eds: K Hawton, P M Salkovskis,
J Kirk, D M Clerk). Oxford University Press, New York, 1989.
23. Hoy SM, Scott LJ. Dapoxetine: in premature ejaculation. Drugs
2010;70:1433-43.
24. Hutchinson K, Cruickshank K, Wylie K. A benefit-risk assessment
of dapoxetine in the treatment of premature ejaculation. Drug Saf.
2012;35(5):359-72.
25. Jaspers L, Feys F, Bramer WM, Franco OH, Leusink P, Laan ET. Efficacy
and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire
Disorder in Women: A Systematic Review and Meta-analysis. JAMA Intern
Med. 2016;176:453-62.
26. Markou S, Perimenis P, Gyftopoulos K, Athanasopoulos A,
Barbalias G. Vardenafil (Levitra) for erectile dysfunction: a systematic
review and meta-analysis of clinical trial reports. International Journal of
Impotence Research, 2004; 16: 470-8.
27. Masters WH & Johnson V. Human Sexual Inadequecy. Churchill, London,
1970.
28. Masters WH & Johnson V. Human Sexual Response. Little, Brown & Co,
Boston, 1966.
29. McMahon CG. Dapoxetine for premature ejaculation. Expert Opin
Pharmacother. 2010;11:1741-52.
30. Men C, Yu L, Yuan H, Cui Y. Efficacy and safety of phosphodiesterase
type 5 inhibitors on primary premature ejaculation in men receiving
selective serotonin reuptake inhibitors therapy: a systematic review and
meta-analysis. Andrologia. 2016 Jan 21. doi: 10.1111/and.12540. [Epub
ahead of print]
31. Rosen C. Prevalence and risk factors of sexual dysfunction in men and
women. Curr Psychiatry Rep. 2000;2:189-95.
32. Smith-Harrison LI, Patel A, Smith RP. The devil is in the details: An
analysis of the subtleties between phosphodiesterase inhibitors for
erectile dysfunction. Transl Androl Urol. 2016;5:181-6.
33. World Health Organization. ICD-10 classification of mental and behavioural
disorders: Diagnostic criteria for Research. World health organization,
Geneva, 1993.
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CLINICAL PRACTICE GUIDELINES

Clinical Practice Guidelines for Sleep Disorders

Ravi Gupta, Sourav Das1, Kishore Gujar2, K K Mishra3, Navendu Gaur4, Abdul Majid5
Dept. of Psychiatry and Sleep Medicine, Himalayan Institute of Medical Sciences, Doiwala, Dehradun, 1Consultant
Psychiatrist and Sleep Specialist, Medica Superspeciality Hospital, Kolkata; Somnos Sleep Clinic, Kolkata. 2Dy. Medical
Superintendent, YCM Hospital, PCMC, Pimpri, 3HOD, Dept. of Psychiatry, JNMC, Wardha, 4Director, Gaur Mental-Health
Clinic, Ajmer-305001, 5Department of Psychiatry, SKIMS Medical College, Srinagar

Participants of expert group on CPG for Sleep Disorders
Ravi Gupta, Kishore Gujar, K K Mishra, Navendu Gaur,
Abdul Majid, Gautam Saha, Amrit Pattojoshi, RK Solanki
INTRODUCTION
Sleep disorders are common, still we have limited data
regarding the prevalence and management of sleep
disorders from India. Although the systematic research
is limited from our country, still case reports from Indian
population suggest that we see all kinds of sleep disorders.
Prevalence of various sleep disorders is shown in Table 1.
Among all, we have population data for two disorders from
Indian adult population- one is Obstructive Sleep Apnea
(OSA) and second is Restless Legs Syndrome (RLS). Sleep
problems have been investigated among Indian children
more frequently through variety of approaches, most
common through the questionnaire based screening in
school-based cohorts.
Knowledge of sleep disorders is essential for psychiatrists
for two reasons.First, some of the sleep disorders are
common in Psychiatric patients. They may be related directly
to the pathophysiology of psychiatric illness, or may be the
consequence of the treatment modalities offered. Insomnia
Address for correspondence:
Dr. Ravi Gupta,
Department of Psychiatry and Sleep Medicine, Himalayan
Institute of Medical Sciences, Doiwala, Dehradun.
E-mail: sleepdoc.ravi@gmail.com
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is a common complaint with a number of Psychiatric
disorders e.g., depression, anxiety, and withdrawal from the
substances that depress cerebral functioning. In addition,
we now have evidence that link the depression, bipolar
disorder and schizophrenia with the disordered circadian
rhythms and many of these patients show delayed sleep
wake phase cycle.Similarly, antidepressants are known
to induce a number of sleep disorders including NREM
parasomnias (sleep talking, sleep walking) as well as REM
parasomnias (REM sleep behavior disorder) and restless
legs syndrome.Antipsychotics may cause weight gain and
thus they may lead to obstructive sleep apnea in a number
of patients.Similarly, opioid users suffer from central sleep
apnea and during withdrawal many of them develop RLS.
Both these conditions may worsen the quality of the sleep.
Secondly, daytime manifestations of a number of sleep
disorders e.g., insomnia, hypersomnia, restless legs
syndrome, sleep apnea mimic that of Psychiatric disorders
e.g., depression, fibromyalgia, chronic fatigue syndrome
and somatoform disorders.
Considering the recent evidences and changes in the
management of sleep disorders,, Indian Psychiatric Society
has decided to update the existing guidelines. However,
few points must be kept in mind while you consider these
guidelines for your practice:
1. These are consensus statements
2. Original research in this area from India is limited. Most
of the literature reviewed has been generated from the
studies involving Caucasian and European population.
They are culturally, phenotypically and genetically
different from Indian population. All three factors-
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DOI:
How to cite this article: Gupta R, Das S, Gujar K, Mishra
KK, Gaur N, Majid A. Clinical Practice Guidelines for Sleep
10.4103/0019-5545.196978
Disorders. Indian J Psychiatry 2017;59:116-38.

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Gupta, et al.: CPGs for sleep disorders

culture, phenotype and genotype influence the sleep Table 1: Prevalence of various sleep disorders in general
patterns, pathophysiology of sleep disorders and their population
management- both pharmacological as well as non- Disorder Prevalence
pharmacological. Insomnia 10‑15%
Hypersomnia Not known
With this background, we will discuss the guidelines Obstructive Sleep Apnea# 14%
regarding management of individual sleep disorders. Restless legs syndrome# 2%
Delayed Sleep wake phase disorder 10%
Advanced Sleep Wake phase disorder 1%
INSOMNIA Shift worker disorder 2%
# Data from Indian population
ICD-10 defines insomnia as a condition where there is a
problem in initiating the sleep, staying asleep or waking up Table 2: Sleep Disorders that may mimic insomnia
early in the morning at least for 3 nights/week for at least Sleep related breathing disorders
1 month. It should be associated with significant distress • Obstructive sleep apnea
and persistent preoccupation with the deficiency of sleep. • Central sleep apnea
Central disorders of hypersomnolence
Narcolepsy
DSM-5 defines insomnia as a condition where a problem has Sleep related movement disorders
been reported in initiating , maintaining the sleep or there • Restless Legs Syndrome
is an early morning awakening. This problem should occur • Nocturnal Myoclonus (sleep starts)
despite adequate opportunities to fall asleep and must • Sleep Related leg cramps
• Sleep related bruxism
occur at least 3 nights a week. It should be associated with
• Sleep related rhythmic movement disorder
significant distress in the personal, social or occupational Parasomnias
life. If it persists for at least 1 month but less than 3 months, • Sleep‑walking
it is considered as episodic; if it persists for at least 3 months, • Sleep terrors
it is considered as persistent insomnia. • Nightmare disorder
Circadian Rhythm Sleep Disorders
• Advanced Sleep Wake Phase disorder
Our understanding regarding insomnia has changed over • Delayed Sleep Wake phase disorder
the years. Earlier we used to differentiate between primary • Shift worker disorder
and secondary insomnia, however, the recent research • Irregular Sleep wake rhythm disorder
Others:
has challenged this belief. Current literature suggests
• Sleep related asystole
that insomnia cannot be considered merely as a symptom • Sleep related epilepsy
of psychiatric disorders. It is rather co-morbid with the • Sleep related laryngospasm
psychiatric and other medical conditions, and if not treated
early, through the process of kindling it becomes chronic Through a careful history and clinical examination, these
which has multiple health and economic implications. conditions can be ruled out (Table 2).

For this reason, in the third edition of International
Classification of Sleep Disorder (ICSD-3), which appeared in
2014, insomnia has been divided into two categories: short
term insomnia disorder and chronic insomnia disorder. In
addition, subtyping of the primary insomnia into adjustment,
psychophysiological, paradoxical and idiopathic that
prevailed till ICSD-2 has been omitted. This has happened
for multiple reasons.First, all the insomnia sufferers have in
common one issue i.e., hyperarousal and second, change in
the sleep related behavior and compensatory mechanisms
were found similar across different insomnia subtypes.
Hence, all the modalities that are used for the treatment of
insomnia are directed towards reducing the hyperarousal.
Assessment and evaluation
Management of the insomnia case starts with the history
taking and general physical examination. It is of paramount
importance as a number of sleep disorders may mimic
insomnia. Hence, having knowledge regarding these mimics
will help the clinician to reach to an accurate diagnosis.
Indian J Psychiatry 59 (Supplement 1), January 2017
While taking the history of a patient with insomnia, special
focus should be provided to the initiation of symptoms,
its course and progression. Information from the
bed-partner/ room-partner who had seen the patient while
asleep should be sought and incorporated.(Table 3).
He should be asked for the daytime symptoms of insomnia,
as in their absence, insomnia can’t be diagnosed. Frequency
of symptoms must be asked along with the duration and
frequency of symptoms per week. It must be ensured
that the patient has adequate opportunities to fall asleep.
Excessive daytime sleepiness must be ruled out. Clues
regarding the predisposing, precipitating and perpetuating
factors of insomnia should be assessed in detail.
It is essential to ask for the sleep pattern while the patient was
asymptomatic and compare it with the sleep schedule during
symptomatic period. Sleep related behavior and rituals must
be asked before and after the symptoms onset as they may
provide a good idea about the possible interventions.
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Table 3: Information regarding a typical night
Information regarding
Sleep Schedule
Nocturnal Awakenings, if any
Pre‑bedtime behavior
Compensatory strategies
Addictive substances
Drugs
Environment of the bedroom
Time spent in bed in awake state
in a whole day
Description
• Time to bed
• Time to fall asleep
• Wake time
• Time taken to get up from bed
• Quality of nocturnal sleep
• Daytime Napping
• Timing
• Duration
• Quality of sleep during naps
• Number of naps
• Regularity of this schedule
• Number of awakenings
• Reasons for awakenings
• Time taken to fall asleep again
• What does he do since evening
• Mental state before going to bed
• Behavior and thoughts during
nocturnal awakenings
• Nature of substance consumed
• Usual timing
• Usual effect: Stimulant/
Somnolent
• Frequency of consumption
• Withdrawal/Intoxication
interfering with sleep
• If person is taking any drug,
then effect of drug on sleep
• Look for possible factors that
can interfere with sleep
Table 4: Other medical disorders that may induce sleep
disturbance
Cardiovascular
• Arrthythmias
• Congestive heart failure
• Myocardial infarction
• Varicose veins
Pulmonary
• Chronic obstructive pulmonary disease
• Interstitial lung disorder
• Scoliosis
GIT
• Peptic ulcer disease
• GERD
• Chronic constipation
CNS
• Intracranial space occupying lesions
• Dementia
• Seizures
• Stroke
• Parkinson’s disease
Neuromuscular disorder
Genitourinary
• Chronic kidney disease
• Benign Prostatic hypertrophy
Musculoskeletal:
• Rhumatoid arthritis
• Connective tissue diseases
Severity of insomnia may be assessed using a brief
questionnaire- Insomnia severity index, available in English
as well as Hindi.

This should be followed by a thorough general physical

Many of the patients with insomnia start worrying while
they are not able to fall asleep in the bed. Dysfunctional
thoughts before the bedtime or while in bed lead to
hyperarousal and they may be assessed using Dysfunctional
Beliefs and Attitudes about Sleep, which is available in
English as well as Hindi Language.
examination and if any system appears dysfunctional, that
should be examined in detail.
Sleep diary provides a good opportunity to assess the sleep-
pattern and helps in differentiating insomnia from circadian
rhythm sleep disorders. (Figure 2).

Many of the medical conditions may induce symptoms that
may mimic insomnia. Hence, the disorders provided in
Table 4 must be ruled out.
Algorithm for the diagnosis of insomnia is depicted in Fig 1.
Effect of the insomnia on the daytime functioning must
be assessed. Special care should be taken to differentiate
between fatigue and sleepiness. Mood during the day must
be assessed. Depression and other psychiatric disorders
that may mimic daytime symptoms of insomnia may be
differentiated by asking “how do you feel during the day
which is followed by a good night sleep?”. If the patient
reports a remarkable improvement, diagnosis of psychiatric
disorder shall be deferred till the insomnia resolves.
If the patient is undergoing any treatment for other medical
disorders (pharmacological as well as non-pharmacological),
its’ effect on the sleep should be examined.
At times, objective data is necessary to reach to a diagnosis
and in those cases actigraphy may be performed. In cases of
chronic insomnia that is not responding to treatment, video-
synchronized 24-channel polysomnography is desirable.
Formulating a treatment plan
Treatment of insomnia is individualized and tailor-made.
For the short term insomnia, pharmacotherapy is indicated,
while for the chronic insomnia, cognitive behavior therapy
for insomnia (CBT-I) is preferred.
Various hypnotic agents are described below. Importance
of behavioral intervention should not be underestimated
and it is better that they should be started even in cases
with short term insomnia. For example, a person might
be having genetic predisposition to insomnia and a recent
stress might have precipitated the insomnia, which could
be perpetuated by the dysfunctional beliefs about sleep or
maladalptive strategies to control it. Common maladaptive

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Gupta, et al.: CPGs for sleep disorders

Paent presenng with complaints suggesve of insomnia

No
Adequate opportunies for sleep No Insomnia
Yes
No
Dayme Symptoms of Insomnia No Insomnia
Yes

Difficulty Iniang Sleep Early morning awakening

Difficulty maintaining Sleep
> 30 min for > 3 Nights/wk > 30 min for > 3 Nights/wk
> 30 min for > 3 Nights/wk

No Total Sleep Time normal

Symptoms of RLS Total Sleep Time Total Sleep
Abnormal acvity at night Snoring present if le to sleep
normal if le to sleep me
Yes Yes decreased
Yes
Yes Screen for NO

OSA
RLS Delayed Sleep Wake Phase Disorder
Seizures
Advanced sleep
Parasomnia wake phase
disorder
High Risk

Nocturnal EEG
REMBD Level 1
NREM
Polysomnography
Normal

NREM
No
Parasomnia
OSA or
Normal
RBD
Confirmed

Terminal Insomnia
Inial Insomnia Middle Insomnia

Duraon

<3 >3
months months

Short term Chronic

Insomnia Insomnia

Figure 1: Algorithm for the diagnosis of Insomnia

strategies that we see include, but not limited to- spending Goals of the therapy
excessive time in bed, start smoking or start drinking 1. Improve the sleep onset latency, total sleep time and
caffeine while awake, spending time on screen while awake reduce awakenings, thus improving sleep efficiency
or spending majority of the time during the day in bed. 2. Improving quality of sleep
3. Ameliorate or significantly reduce the daytime
Wherever indicated, opinion from a relevant specialist symptoms of insomnia
may be sought. If there is evidence of sleep disorders 4. Sustain the effect of treatment and reduce the chances
that mimic insomnia, management should be directed to of the relapse
those disorders, rather than the insomnia. In some cases,
insomnia is co-morbid with these sleep disorders, and in Choice of treatment settings
these cases, both should be treated. Treatment of insomnia is usually offered on an outpatient

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Figure 2: Sleep diary depicting long sleep onset latency with normal total sleep time when the patient is following natural pattern
of sleep. However, the patient gets the sleep late in the night and wakes up late in the morning. This data suggests delayed
sleep wake phase disorder

basis. Hospitalization may rather worsen the condition by
enhancing hyperarousal. However, in some patients it may
improve sleep by removing environmental factors and may
provide a clue to the underlying pathophysiology.
Pharmacological treatment
Pharmacological treatment for the insomnia is limited to short-
term insomnia and they are not routinely recommended for
the management of chronic insomnia. A wide variety of drugs
is available that may induce sleep e.g., benzodiazepines,
Benzodiazepine receptor agonists, sedating antidepressants,
second generation antipsychotics, antihistaminics, melatonin
and its agonists and orexin receptor antagonists. Table 5 shows
the factors that influence the choice of a particular drug.
Benzodiazepinesand benzodiazepine receptor agonists
(BzRA) are usually divided into short, intermediate and
long acting and one of them may be chosen based upon
the case. In general, short acting are preferred when the
patient is having difficulty in sleep initiation, intermediate
acting when the patient has difficulty in maintaining the
sleep and long acting when the patients complain of early
morning awakening. However, intermediate and long acting
agents may have residual daytime effects and may produce
the somnolence during the day (Table 6).
Melatonin and its agonists include the melatonin itself
and the molecules that act on MT1 and MT2 receptors.
Melationin is available as 3 mg tablet formulation.
This may be used to induce sleep, however, data do not
support its efficacy as a hypnotic agent. It is rather used
as a chronobiotic. Melatonin receptor agonists- ramelteon
(8-24 mg/day) and agomelatine (25-50 mg/day) are available
in India. Remelteon is a short-acting-drug with half-life of
around 3-4 hours. It shows an improvement in the time to fall
asleep with minimal adverse effects.Agomelatine is another
molecule that in addition to having an agonist action on
melatonin receptors, also has antagonist action on 5-HT2C
receptors. It has been found effective in improving both
sleep and mood in clinical trials, and because of it’s short
half life (1-2 h) is free from daytime somnolence.
Orexin-receptors antagonists have recently been discovered
for the management of insomnia. Controlled trial data is
available for one of the molecule i.e., Survorexant. It has
been found to improve total sleep time with variable findings

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on the nocturnal arousals and time spent awake after sleep
onset. Usual prescribing dose varies between 10-40 mg/day.
Common adverse effects include nausea abnormal dreams.
Sedating antidepressants e.g., tricyclics, trazodone and
mirtazapine may be used if there is comorbid psychiatric
disorder that warrants their use. In addition, they may also
be preferred when adverse effects of the benzodiazepines
and BzRAs are not tolerable. However, there are insufficient
evidences for their efficacy in insomnia.
Antihistaminicdrugs are available as over-the-counter drugs,
and they are commonly used for self medication.However,
data regarding their efficacy in insomnia is limited. However,
a tricyclic drug Doxeipin has been approved for the treatment
of insomnia in low doses (10 mg). At this dose, it primarily
acts on the H1receptors and work as an antihistaminic.
Antipsychotics are used off-label for the treatment of
insomnia, particularly chlorpromazine, clozapine, olanzapine
and qutiapine. However, we do not have data regarding their
efficacy as hypnotic agents. In addition, while prescribing
them, it is essential to consider potential adverse effects
e.g., metabolic syndrome and extrapyramidal symptoms.
Long term pharmacotherapy
Although the pharmacotherapy is not routinely
recommended for the long term treatment in view of
availablibility of non-pharmacological therapies, still, data
Table 5: How to choose a drug from the available
molecules?
Age of the patient and risks associated with sedation
Comorbid psychiatric and other medical disorders
Pharmacokinetic properties of the molecule in question
Drug interactions with other medication that the patient is taking
Adverse effects of the drug in question: short term as well as long term
Availability of the molecule
Cost of the drug
Allergy to the molecule in question
is available for treatement with Z drugs for as long as 6
months without any major adverse effects. Considering the
limited availability of trained CBT-I therapist, consensus
was reached that in certain circunstances where CBT-I
is not possible for any reason, pharmacothepray may be
institutedfor long term.
Non-Pharmaclogical therapies
Cognitive behaviour therapy for Insomnia (CBT-I) is
the mainstay of therapy for chronic insomnia. It is a
multicomponent therapy that includes education regarding
sleep physiology, sleep hygiene, addressing dysfunctional
beliefs, stimulus control therapy, sleep restriction and
relaxation training.Each of these components may be used
as a primary focus in a given patient which makes this
therapy highly individualized. In general, goal of the therapy
is to reduce the hyperarousal, hence, educating the patient,
cognitive restructuring (to address dysfunctional belief) and
relaxation are necessary in almost all patients. CBT-I has been
found effective for long term management of insomnia in
the randomized controlled trials comparing it with hypnotic
agents. It has been repeatedly shown that though, it takes
some time to show its effects, once they appear, they are
longer lasting as compared to pharmacotherapy and also
reduce the chances of relapse.One of the major advantages of
the CBT-I is the fact that it has also been found useful in cases
of insomnia co-occurring in context of medical disorders.
Since the CBT-I is time consuming and requires the expertise,
it has been tried to be delivered through internet, computer
and in groups.Though the computerized CBT-I has been
found superior to the placebo and pharmacotherapy, still it’s
efficacy has been found low when compared to the face to
face CBT-I. Administration of CBT-I in a group has also been
tried, with the results similar to the computerized CBT-I.
Results of sleep education and sleep hygiene alone have
been found to have limited value unless they are associated
with some other component of the CBT-I.

Table 6: Benzodiazepines and Benzodiazepine Receptor Agonists

Molecule Half Life (hr) Dose (mg/d) Formulations Common Adverse effects
Benzodiazepines
Oxazepam 3‑20 10‑30 mg Tablet Memory lapses, daytime sleepiness,
ataxia, fall, automatism, slurred speech
Trialzolam 1.5‑5.5 0.5‑1 mg Tablet
Lorazepam 10‑20 1‑4 mg Tablet/Injection
Alprazolam 6‑20 0.25‑1 mg Tablet/Sustained released
Diazepam 20‑50 5‑20 mg Tablet/Injection
Clonazepam 18‑40 0.5‑2 mg Tablet/Mouth dissolving
Nitrazepam 30‑40 5‑10 mg Tablet
Benzodiazepine
Receptor Agonists
Zaleplon 1 5‑10 Tablet Memory lapses, hallucinations,
Eszopiclone 5 1‑2 Tablet paradoxical excitement
Zolpidem 2‑4 5‑10 Tablet/Extended release/Sublingual low
dose/Sublingual high dose/Oral spray

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Exercise, especially the aerobic exercise along with the
sleep hygeine has been found to be beneficial for the
sleep and daytime activity. It has been found to reduce the
time taken to fall asleep and improve the sleep efficiency
in randomized control trials.Thus, patients should not be
advised not to engage into any exercise before bed-time, as
conventionally thought. Rather they should be allowed to
analyse their sleep reactivity towards the exercise and if is
found to interfere with sleep, then they should be advised
not to get engaged into it before bedtime.
One of the focus of the therapy is to reduce the total time
spent in bed in an effort to fall asleep by sleep restriction.
Evidence is less robust regarding the utility of the sleep
restriction therapy.However, a recent review suggested
that sleep restriction therapy is one of the most effective
components of the CBT-I.This must not be used in cases
of bipolar disorders and epilepsy as it may worsen the
comorbid medical condition.
In Indian context, since patients have been found focussing
on the daytime worries, rather than on the sleep, problem
solving technique may be added.Recently, mindfulness
based relaxation therapy has been found to improve the
sleep.Mindfulness based stress relaxation (MBSR) has
been found equally efficacious to the face to face CBT-I,
pharmacotherapy and better than sleep hygiene alone.This
has been found more efficacious when it has been included
as a component of CBT-I.
Management as per the different phases of illness
On of the major issues with the patients with chronic
insomnia is that they desperately want to sleep soon after
the initiation of treatment. However, CBT-I takes longer time
to improve the situation because it is delivered in sessions.
And each session has a focus which is guided by prevailing
sleep problems since last session. During CBT-I patient is
expected to maintain a sleep diary and change his cognition
and behavior. Many of the patients are not able to do that. In
those cases, the treatment is started with pharmacotherapy
along with the CBT-I. Gradually, the pharmacotherpay is
tapered and patient remains only on the CBT-I. Thus, patient
benefits from the immediate response of hypnotics that
reduces the burden and hyperarousal in addition to long
term benefits of CBT-I. Though many sleep specialists are
practicing it, still it has not been thoroughly investigated.
When to stop treatment
Though we do not have any literature on this issue, still,
for the short term insomnia, patient should be requested
to give drug holidays intermittently and to restart the
treatment when the symptoms appear again. CBT-I may
be discontinued once the sleep of the patient is stabilized
for at least 4 weeks, though this number has been chosen
arbitrarily.
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Special population
Pharmacotherapy should be cautiously advised to the
elderly because of the drug interactions and adverse
effect profile. This should also be cautiously used in
children and patients with other medical disorders for
the same reasons. CBT-I is not possible in patients with
neurocognitive deficits and non-compliant patients,
hence they should not be started it without assessing
their motivation.
Pregnancy: Duing first trimester it is best to avoid all
medications. In disabling cases, sedating antihistaminitcsmay
be used for the shortest possible period.
Lactation: Amount of psychotropicdrugs that is excreted in
milk varies from molecule to molecule. Reader is advised
to consult the pharmacology book for details regarding
individual molecule.
HYPEROSMNIA
Alertness is an integral necessity for learning, performance
and safety. Excessive daytime sleepiness impairs productivity
and exponentially increases the risk of accidents, particularly
in occupations like transportation, military, healthcare,
factory workers etc. excessive sleepiness is reported by
10-25% of the general population in different parts of the
world. However, as of now there are no prevalence studies
from India on hypersomnia/ excessive sleepiness.
International Classification of Sleep Disorder, 3rd edition
(ICSD 3) defines daytime sleepiness as: “the inability to
stay awake and alert during the major waking episodes of
the day, resulting in periods of irrepressible need for sleep
or unintended lapses into drowsiness or sleep”. Sleepiness
varies in severity and is more common during sedentary,
boring, and monotonous situations that require little
active participation. Some patients are aware of increasing
sleepiness before falling asleep, whereas others can fall asleep
with little or no prodromal symptoms (“sleep attacks”).
The most common cause of excessive daytime sleepiness
(EDS) in modern day world is the combination of suboptimal
duration of sleep, poor sleep hygiene, and changing
work schedules. In addition, various sleep disorders like
obstructive sleep apnea, circadian rhythm sleep disorders
and periodic limb movement disorder may be associated
with excessive daytime sleepiness.
Primary causes of hypersomnolence have been classified
under the heading of “Central disorders of hypersomnolence”
in ICSD 3. The various central causes of hypersomnolence
according to different classification systems is given in
the table 7 below and Algorithm to approach a case of
hypersomnia is given in Fig 3.
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Table 7: Comparative terminologies of causes of hypersomnolence between ICD‑10 and ICSD‑3

ICSD 3 ICD 10 ICD 10 code:
Narcolepsy Type 1 Narcolepsy With Cataplexy G47.411
Narcolepsy Type 2 Narcolepsy Without Cataplexy G47.419
Idiopathic Hypersomnia Idiopathic Hypersomnia With Long Sleep Time G47.11
Idiopathic Hypersomnia Without Long Sleep Time G47.12
Kleine‑Levin Syndrome Recurrent Hypersomnia G47.13
Hypersomnia Due to a Medical Disorder Hypersomnia Due to Medical Condition G47.14
Hypersomnia Due to a Medication or Substance F11‑F19
Hypersomnia Associated with a Psychiatric Disorder Hypersomnia due to other mental disorder F51.13
Insufficient Sleep Syndrome Insufficient sleep syndrome F51.12
Primary Hypersomnia F51.11
Other hypersomnia not due to a substance or F51.19
known physiological condition

Symptoms of Excessive insufficient sleep, inadequate Psychoeducation/ Sleep

Daytime Sleepiness sleep hygiene, job or familial Hygiene/ Behavior Therapy/
Yes
stressors and work schedules CBTi
from history

Recurrent hypersomnia, e.g. No

Klein Levin syndrome (usually
associated with behavioral
change, hyperphagia,
irritability)
Yes
Polysomnography Within
Normal limits
Episodic/ recurrent
Suggestive history for hypersomnia:
Yes No
Irresistable urge for sleep in daytime (or
in middle of activities)/ sleep attacks/
cataplexy/ hypnagogic or hypnapompic
Rating scales: hallucinations/ sleep paralysis/ REM
Epworth Sleepiness Scale behavioral disorders/ prolonged sleep
Sleep diary Yes time/ confusional arousals

Full night attended Level I

Polysomnography preferably Objective evidence of OSA/ Treat accordingly
with video recording CSA/ PLMD/ Parasomnias
Yes
Followed by Multiple Sleep
Latency Test next day With cataplexy or CSF
MSLT findings: Hypocretin 1 conc. either <=
MSLT: SL<=8 min, >= 2 SOREMPs Yes 110pg/mL or <1/3 of mean
reference values
MSLT findings:
MSLT: SL<=8 min, < 2 SOREMPs
Yes No
Narcolepsy Narcolepsy
Total 24 hr sleep time >=660 Type 1 Type 2
Idiopathic
mins by 24 hour PSG/ wrist Hypersomnia
actigraphy +sleep log Yes

Underlying medical
Yes Underlying medical condition Hypersomnia due to condition diagnosed by MRI/
judged to be directly causing a medical disorder SPECT/ Immunology etc.
the excessive sleepiness Yes
Yes
No
Attributable to sedative Hypersomnia due to a
Primary Narcolepsy
medications, alcohol or drugs medication or
Narcolepsy secondary to
of abuse Yes substance
(Type 1 or 2) medical
condition
(Type 1 or 2)
Attributable to underlying Hypersomnia
psychiatric conditions like associated with a
moods disorders, somatic Yes psychiatric disorder
symptom disorder etc.

Figure 3: Algorithm for the diagnosis of Hypersomnia

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Hypersomnias of central origin
Narcolepsy type 1: caused by a deficiency of hypothalamic
hypocretin (orexin) signaling. Excessive daytime sleepiness
and signs of REM-sleep dissociation are the characteristic
features of narcolepsy, however, the most specific feature
is cataplexy (defined as more than one episode of generally
brief (< 2 minutes), usually bilaterally symmetrical sudden
loss of muscle tone with retained consciousness). There
are repeated daily episodes of an irrepressible need to
sleep or lapses into sleep (sleep attacks). Most patients
awaken refreshed after a sleep episode but begin to feel
sleepy again after variable times. Many narcolepsy patients
have lapses in vigilance, sometimes in combination
with automatic behavior, such as writing gibberish or
interrupting a conversation with a completely different
topic. Apart from cataplexy and sleep attacks, 33% to 80%
of narcolepsy patients have hypnagogic hallucinations and/
or sleep paralysis. Hypnagogic hallucinations are defined
as vivid dreamlike experiences occurring at the transition
from wake to sleep. Typically, hypnagogic hallucinations
have a multimodal or “holistic” character, often combining
visual, auditory, and tactile phenomena. Hypnopompic
hallucinations are similar but occur at sleep to wake
transitions. Sleep paralysis describes the disturbing
temporary inability to move voluntary muscles at sleep-
wake transitions. Despite being awake and conscious of
the sleeping environment, it is impossible for subjects to
move their limbs or even open their eyes. The experience
may last for several minutes and can be very distressing.
Other symptoms may include ptosis, blurred vision, and
diplopia, presumably as a result of sleepiness. Obesity is
another common symptom of narcolepsy.
Narcolepsy type 1 due to a medical condition: This condition
is primarily associated with central nervous system (CNS)
disorders, including autoimmune or paraneoplastic
disorders associated with anti-Ma2 or antiaquaporin4
antibodies, and tumors or other lesions of the hypothalamus
or severe head trauma.
Narcolepsy type 2: is characterized by excessive daytime
sleepiness and abnormal manifestations of REM sleep on
polysomnography/MSLT [mean sleep latency less than or
equal to eight minutes and two or more sleep onset REM
periods (SOREMPs) on an MSLT (or one SOREMP on an MSLT
and one on the preceding nocturnal polysomnogram)].
Cataplexy is absent, although some atypical sensations of
weakness triggered by unusual emotions such as stress
and anger may be reported. Refreshing daytime naps are
characteristic. Sleep paralysis, hypnagogic hallucinations,
or automatic behavior, memory lapses, automatic behavior,
ptosis, blurred vision, and diplopia may be present.
Narcolepsy type 2 due to a medical condition:  Neurologic disorders
associated with narcolepsy type 2 include tumors or sarcoidosis
of the hypothalamus, autoimmune or paraneoplastic disorders
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associated with anti-Ma-2 or anti-aquaporin-4 antibodies,
multiple sclerosis, myotonic dystrophy, Prader-Willi syndrome,
Parkinson disease, and head trauma.
Idiopathic hypersomnia: is characterized by excessive
daytime sleepiness that occurs in the absence of cataplexy,
is accompanied by no more than one SOREMP on MSLT and
preceding polysomnogram combined, and is not adequately
explained by another disorder. Sleep drunkenness,
consisting of prolonged difficulty waking up with repeated
returns to sleep, irritability, automatic behavior, and
confusion may be present. Subjects typically do not easily
awaken to alarm clocks and frequently use special devices
or procedures to wake up. Naps are generally long, often
more than 60 minutes, and described as unrefreshing by
46% to 78% of patients. Associated symptoms which suggest
a dysfunction of the autonomic nervous system may be
present. These symptoms include headache, orthostatic
disturbance, perception of temperature dysregulation, and
peripheral vascular complaints (Raynaud-type phenomena
with cold hands and feet).
Recurrent Hypersomnia: Kleine-Levin syndrome is
characterized by recurrent episodes of excessive
sleepiness,however, associated cognitiveand behavioral
disturbances are not uncommon. A typical episode
lasts a median 10 days (range, 2.5–80 days), with rare
episodes lasting several weeks to months. Usual reported
triggering factors for the first episodes are infection or
alcohol intake, with further episodes recurring every
1–12 months (median three months) for years. During
episodes, patients may spend as long as 16 to 20 hours
per day in sleep, and they usually wake-up only for the
natural calls (incontinence is not observed). They remain
arousable, but are irritable if prevented from sleeping.
When they are awake during episodes, most patients
appear exhausted, indifferent, confused with psychomotor
retardation. Anterograde amnesia is typical and most of the
patients report derealization. A larger chunk of patients eat
ravenously (66%, although one third eat less), nearly half of
them turn hypersexual (53%, principally men), may show
childish behavior and nearly half appear depressed (53%,
predominantly women). They often become anxious when
left alone and after seeing strangers, and nearly third of them
experience hallucinations and delusions (30%). Importantly,
patients are completely asymptomatic in between episodes.
Hypersomnia Due to a Medical Disorder:Patients with
this disorder have excessive nocturnal sleep, daytime
sleepiness, or excessive napping that is attributable to
a coexisting medical or neurological disorder. Daytime
sleepiness may be of variable severity and may resemble
that of narcolepsy (i.e., refreshing naps) or idiopathic
hypersomnia (i.e., long periods of unrefreshing sleep).
Other symptoms of narcolepsy e.g., sleep paralysis,
hypnagogic hallucinations and automatic behavior may
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be present. Hypersomnia due to a medical disorder is only Management

diagnosed if the medical condition is judged to be directly
causing the excessive sleepiness. Hypersomnolence has
been described in association with a number of conditions
e.g., metabolic encephalopathy, head trauma, stroke,
brain tumors, encephalitis, systemic inflammation (e.g.,
chronic infections, rheumatologic disorders, cancer),
genetic disorders, and neurodegenerative diseases.
Hypersomnia due to a medication or substance:Patients
with this disorder have excessive nocturnal sleep, daytime
sleepiness, or excessive napping that is attributable to
sedating medications, alcohol, or drugs of abuse. This
diagnosis also includes hypersomnolence associated
with withdrawal from amphetamines and other stimulant
drugs.
Subtypes
Hypersomnia due to sedating medications:  desired or regarded as the societal norm ie. share a common
Hypersomnia due to substance abuse:  underlying chronophysiologic basis.
Hypersomnia due to stimulant withdrawal:  1. Time Zone Change (Jet Lag) Syndrome
Hypersomnia associated with a psychiatric disorder:
Patient may report increased duration of nocturnal sleep
associated with daytime sleepiness or excessive napping.
In addition, they often complain of poor quality and
nonrestorative sleep. Patients are often intensely focused
on their hypersomnolence, and psychiatric symptoms
may become apparent only after prolonged interviews or
psychometric testing. Associated psychiatric conditions
include mood disorders, conversion or undifferentiated
somatoform disorder, and less frequently other mental
disorders such as schizoaffective disorder, adjustment
disorder, or personality disorders.
Subtypes:
Hypersomnia associated with mood disorder
Hypersomnia associated with a conversion disorder or somatic
symptom disorder
Insufficient sleep syndrome:Many people curtail a small
portion from their normal sleep duration for prolonged
periods owing to societal or professional demands. Since
sleep deprivation has cumulative effect, they remain in a
state of chronic partial sleep deprivation that is insufficient to
maintain normal levels of alertness and wakefulness. Physical
examination reveals no medical explanation for the patient’s
sleepiness. A detailed history of the sleep pattern reveals that
patient is not spending adequate time in sleep and that he
has curtailed his sleep in past few days/months. Sleep time
that is markedly extended on weekend nights or during
holidays compared to weekday nights is also suggestive
of this disorder. Individuals with this condition may show
cognitive and behavioral symptoms e.g., irritability, attention
deficits, distractibility, reduced drive, anergia, dysphoria,
fatigue, impatience, incoordination, and tiredness.  consists of varying degrees of difficulties in initiating or
A. Pharmacotherapy: Pharmacotherapeutic options for the
management of hypersomnia are depicted in Table 8.
B. Behavioral Treatment:
• Education about type of hypersomnia, course, prognosis
and management principles
• Regular frequent nap times of 10-20 mins at 2-4 hour
intervals during the day
• Emphasize need for a regular nocturnal sleep schedule
• Try to obtain 9 hours of nocturnal sleep
CIRCADIAN RHYTHM SLEEP DISORDERS
The circadian rhythm sleep disorders comprise of following
disorders having major feature is a misalignment between
the patient’s sleep pattern and the sleep pattern that is
2. Shift Work Sleep Disorder
3. Irregular Sleep-Wake Pattern
4. Delayed Sleep-Phase Syndrome
5. Advanced Sleep-Phase Syndrome
6. Non-24-Hour Sleep-Wake Disorder
7. Circadian Rhythm Sleep Disorder Not Otherwise
Specified
Diagnostic subtypes can be specified with the diagnosis of
intrinsic type (due to neurologic disease) or extrinsic type
(due to environmental or social circumstances) Severity
Criteria: Mild: Moderate: Severe:
Duration Criteria: Acute: Subacute: Chronic:
Major problem among all CRSDs is the inability to fall asleep or
staying awake when desired or expected. Since sleep episodes
occurring at inappropriate times, the corresponding wake periods
also seen at undesired times. Therefore, the patient complains
of insomnia or sleepiness but importantly both of them are
occurring at inappropriate times. For most of the CRSDs, once
sleep is initiated, the major sleep episode is of normal duration
with normal architecture. However, if any other sleep disorder
appears to influence the sleep timing, diagnosis of CRSD should
be deferred.For example patients with inadequate sleep hygiene
may show some degree of shift in sleep and wake timing. Hence,
CRSD should be diagnosed only when the symptoms can be
ascribed to the major shift in timing of sleep.
1. Time Zone Change (Jet Lag) Syndrome: Synonyms and
Key Words: Jet lag, transmeridian flight desynchronosis, air
travel, transmeridiandyschronism.
Essential Features: Time zone change (jet lag) syndrome

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Table 8: Pharmacotherapy for Hypersomnia

Used for: Drug Mechanism of action Dose range (mg/day) Pediatric use
Hypersomnia Amphetamine stimulants 5‑60 mg Not recommended in pts<3 years
in Narcolepsy, Methyphenidate stimulants 20‑40 mg in adults; Not recommended in pts<6 years.
Idiopathic 5‑20 mg in children Parameters of growth are should be
hypersomnia, etc. regularly monitored in children
Modafinil non‑amphetamine 100‑400 mg SECNE
wakefulness‑promoting
medication
Armodafinil  (R)‑ enantiomer of modafinil with 50‑250 mg SECNE
a longer half‑life.
Sodium oxybate rapidly acting sedative/hypnotic/ 4.5‑9 g per night SECNE
(also used for Cataplexy, anesthetic medication.
sleep paralysis, hypnagogic
hallucinations)
Selegiline MAO‑B inhibitor that is 5‑10 mg SECNE
metabolized to amphetamine and
methylamphetamine
Atomoxetine selective noradrenaline reuptake 10‑25 mg generally well tolerated in children and
inhibitor (NARI) adolescents
Reboxetine selective noradrenaline reuptake 10 mg SECNE
inhibitor (NARI)
Ritanserin 5‑HT2 antagonist 5‑10 mg SECNE
Cataplexy Fluoxetine Selective serotonin reuptake 10‑40 mg Safety and effectiveness assessed in
inhibitor (SSRI) children aged 8‑18 yrs with major
depressive disorder and 7‑18 yrs with
OCD
Venlafaxine# serotonin‑norepinephrine reuptake 75‑375 mg SECNE
inhibitor (SNRI)
Protriptyline Tricyclic antidepressant (TCA) 10 mg SECNE
Viloxazine selective norepinephrine reuptake 50‑200 mg SECNE
inhibitor (NRI)
Imipramine Tricyclic antidepressant (TCA) 25‑200 mg SECNE
Clomipramine Tricyclic antidepressant (TCA) 25‑200 mg Can be used in children aged 10 years
and above
Desipramine Tricyclic antidepressant (TCA) 25‑200 mg Not approved for use in children
Recurrent Lithium* Mood Stabiliser 300‑900mg Special caution advised
hypersomnia (Klein
Levin Syndrome)
SECNE – Safety and effectiveness in children not established; NE – Not established *Carbamazepine and valproate can also be used for KLS, some benefit noted
in behavioral symptoms, but no consistent benefit observed in hypersomnia #Duloxetine and desvenlafaxine can also be used to treat cataplexy, though there is
lack of formal research data at present.

maintaining sleep, excessive sleepiness, decrements in
subjective daytime alertness and performance, and somatic
symptoms (largely related to gastrointestinal function)
following rapid travel across multiple time zones.
2. Shift Work Sleep Disorder: Symptoms of insomnia or
excessive sleepiness are seen in association of work shifts.
These patients are often having work shifts that defy the
natural sleep-wake cycle and thus they feel sleepy or unable
to fall asleep at inappropriate time, e.g., while on work or
after reaching home, respectively.
3. Irregular Sleep-Wake Pattern: These patients have
inconsistent timings of sleep and wakefuleness, although
the total duration of sleep remains normal in 24 hours.
When their circadian rhythm is examined through sleep
diary or actigraphy, it appears constantly changing.
4. Delayed Sleep-Phase Syndrome: In this condition, sleep
time and wake time both are delayed in relation to the
environmental timing, however, total sleep time remains
adequate (Fig 1). These patients can’t fall asleep till late in the
night and wake up late in the morning having optimal duration
of sleep. If they go to bed early in the evening, they have a long
sleep onset latency and if they are made to wake up early in
morning, they have reduced awareness and feel sleep.
5. Advanced Sleep-Phase Syndrome: This is opposite of the
delayed sleep phase disorder. These patients starts feeling
sleepy early in the evening, spent optimal time in sleep but
wake up early. If they are made to stay awake till late in
night, they show reduced vigilance.
6. Non-24-Hour Sleep-Wake Syndrome
When seen through sleep diary and Actigraphy, these
patients have optimal duration of sleep, although the timing
of sleep appears delayed by 1-2 hours each day.

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In January of 2014, the FDA approved the melatonin agonist
HetliozTM (tasimelteon) for the treatment of N24SWD among
the blind. This is the first FDA-approved drug for any CRSWD.
Diagnosis of CRSD
Polysomnography and Morningness-Eveningness
Questionnaire is not routinely indicated for any of the
CRSDs. Actigraphy is recommended for the delayed sleep
wake phase disorder and advanced sleep wake phase
disorder but may also be used to diagnose other CRSDs.
Sleep diary must be maintained to diagnose all CRSDs.
Actigraphy is a good tool to measure the progress.
Management
Planned naps are recommended for Shift worker disorder.
Timed bright light therapy is useful for shift worker disorder
and delayed sleep wake phase disorder. Jet lag disorder can
be managed by timed melatonin administration. Hypnotics
may be used to induce sleep in Shift worker disorder,
however, stimulants are usually not recommended for the
management of CRSDs.
RESTLESS LEG SYNDROME
Restless legs syndrome/Willis-Ekbom disease (RLS/
WED) is characterized by an urge to move legs that
is often accompanied by dysesthesias in the muscles.
The urge improves with the movement of the legs or
application of a counterirritant. Symptoms are seen only
in the evening and rest worsens the symptoms.A number
of conditions like nocturnal leg cramps, habitual leg
movement, varicose, arthralgia, positional leg discomfort
and leg edema must be excluded before making the
diagnosis of RLS. This condition interferes with the sleep
significantly. In some patients, significant sleep fatigue
or poor concentration is reported in absence of RLS,
but with polysomnographic evidence of periodic limb
movements during sleep (PLMS), in all such cases the
term periodic limb movement disorder (PLMD) is used.
It is an autosomal dominant, sensorimotor disorder in
which patient complains of a peculiar creepy or crawling
sensation in the extremities Prevalence varies between
2-11% across different studies depending upon the
geographical locations and populations included.
Assessment & evaluation in case of RLS
The diagnosis of restless leg syndrome is primarily
based on the symptoms reported by the patient or the
observer. Nocturnal polysomnography may help in the
diagnosis by having PLMs in the recording. Serum iron
level estimation may be helpful as iron is a co-factor
for tyrosine hydroxylase which is essential for synthesis
of dopamine.The Cambridge Hopkins RLS diagnostic
questionnaire(CHRLSQ )and its Hindi version can be
used during surveys and epidemiological studies.
Looking for risk factors viz - elderly population, low iron
Indian J Psychiatry 59 (Supplement 1), January 2017
level, Parkinsonism disorder, end stage renal disease is
important.
Management
The selection of therapy depends upon a number of
factors, including disease severity, patient age, co
morbidities (e.g., pain, depression, anxiety and history of
impulse control behaviours), drug side effects and patient
preferences.
1. Non – pharmacological
Proper maintenance of sleep hygiene, exercise, restriction
of coffee beverages, pneumatic compression stocking help
in the symptom reduction
Behavioral strategies — Use of the following interventions
is supported primarily on the basis of clinical experience in
some cases, and small randomized trials
• Avoidance of aggravating factors, including
consideration of withdrawal of possibly predisposing
medications
• Moderate regular exercise
• Reduced caffeine intake
• For symptomatic relief – walking, bicycling, soaking the
affected limbs, and leg massage, including pneumatic
compression
• Short daily hemodialysis for patients with end-stage
renal disease.
Avoidance of aggravating factors — Sleep deprivation is
known to aggravate symptoms of restless legs syndrome/
Willis-Ekbom disease (RLS/WED) in many patients, and
general principles of sleep hygiene should be reviewed.
Psychotropic drugs e.g., antidepressants, antipsychotics
and other dopamine-blocking antiemetics such
as metoclopramide, and sedating antihistamines (including
those found in nonprescription medications) may lead to
emergence of RLS/WED or worsening of prior symptoms.
Most antidepressant classes have been associated withRLS/
WED, including tricyclics, selective serotonin reuptake
inhibitors, and serotonin-norepinephrine reuptake inhibitors.
Discontinuation of antidepressantsmay not be possible
among all patients. In all such cases, symptoms of
secondary RLS/WED should be treated in the same
way as primary RLS/WED. Bupropion is an alternative
antidepressant that may be less likely to induce or
worsenRLS/WED.
Iron replacement
Serum ferritin concentration lower than 45 to
50 mcg/L (ng/mL) has been associated with an increased
severity of restless legs syndrome. If the serum ferritin
level is lower than 75 ng/ml, iron replacement is
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suggested. However, care must be taken not to induce
iron overlaod.
Both oral iron therapy as well as intravenous iron have been
found effective in treatment of RLS.
2. Pharmacological
The major classes of drugs used include dopaminergic
agents, alpha-2-delta calcium channel ligands, opioids, and
benzodiazepines
Chronic persistent symptoms  relief is obtained. Most patients require at least 2 mg,
 Chronic persistent restless legs syndrome is defined as RLS
that is frequent and troublesome enough to require daily
treatment, with symptoms usually occurring at least twice
a week on average and resulting in moderate or severe
distress.
Choice of therapy — Patients who do not respond to non
pharmacologic therapy and correction of iron deficiency,
pharmacologic treatment with a dopamine agonist or an
alpha-2-delta calcium channel ligand is recommended.
• For patients with very severe  RLS/WED,  co morbid
depression, or obesity / metabolic syndrome, a dopamine
agonist is preferred over other drugs as initial therapy.
• For patients with comorbid pain, anxiety, or insomnia
or a history of impulse control disorder or addiction
associated with use of a dopamine agonist an alpha-2-
delta calcium channel ligand. Is preffered
• Most other patients, initial trial an alpha-2-delta calcium
channel ligand because of the of augmentation with
dopamine agonists, but other potential side effects of
the various drugs should also be considered. In general,
older patients are more prone to side effects of alpha-
2-delta ligands. If the first drug chosen is ineffective
or poorly tolerated, then a drug of the other class
should be tried , including levodopa, benzodiazepines,
and opioids, but generally these are reserved for
intermittent use or in patients with more refractory
symptoms.
Dopamine agonists — A number of dopamine agonsits are
available in market e.g., cabergoline, lisuride, pergolide,
pramipexole, ropinirole,rotigotine, and sumanirole. All
except sumanirolehave been found superior to placebo. In
two trials, cabergoline and pramipexole were superior to
levodopa for improvement in disease severity as measured
by the International Restless Legs Syndrome Study Group
(IRLS) rating scale.
Pramipexole and Ropinirole — Action of pramipexole and
ropinirole  usually starts 90 to 120 minutes after intake.
Therefore, these medications should be started two hours
before RLS/WED symptoms start. The recommended doses
are as follows:
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• Pramipexole  0.125 mg once daily. The dose may be
increased by 0.125 mg every two to three days until
relief is obtained. In a clinical trial, all three doses
of pramipexole (0.25, 0.50, and 0.75 mg daily) were
equally effective, and some patients responded to the
initial dose of 0.125 mg daily. However, side effects
were more common with the 0.50 mg and 0.75 mg
daily doses. Therefore, it is expected that 0.25 mg daily
has the best therapeutic margin. Most patients require
0.5 mg or less, but doses up to 1 mg may be needed.
• Ropinirole  0.25 mg once daily. The dose may be
increased by 0.25 mg every two to three days until
and doses up to 4 mg may be needed. The maximum
recommended dose is 3 mg in patients with end-stage
renal disease on hemodialysis.
Rotigotine — Rotigotine is a non-ergot dopamine
agonist that is formulated as a 24-hour transdermal patch
.Transdermal rotigotine is a once-daily patch that is
typically started at 1 mg/24 hours and titrated upwards to a
maximum dose of 3 mg/24 hours. Application site reaction
is the most common adverse effect of rotigotine, reported
by 40 to 50 percent of patients.
Alpha-2-delta calcium channel ligands — Gabapentin
enacarbil, gabapentin, and pregabalin are alternative
choices for patients with chronic persistent RLS.
Gabapentin enacarbil — Several randomized, placebo-
controlled studies have demonstrated that gabapentin
enacarbil is effective in reducing RLS/WEDsymptom severity.
The recommended dose of gabapentin enacarbil for
RLS/WED is 600 mg, taken in the early evening
Gabapentin —Limited data suggest gabapentin may be
effective in RLS/WED.
Pregabalin — Pregabalin in the doses of 75-300 mg/day
found effective in treatment of RLS.
Duration of therapy 
RLS/WED is often a lifelong disease, but the optimal and
safe duration of pharmacologic therapy has not been well
established. Most of the supporting data are based on
relatively short (≤12-week) randomized trials, with fewer
long-term extension studies supporting efficacy for 6
to 12 months of therapy with either a dopamine agonist
or gabapentin enacarbil.
Special populations
Pregnancy and lactation — Management of restless
legs syndrome during pregnancy should be individualized
based on symptom severity, comorbidities such as
depression or anxiety, and patient preferences. Many
patients can be managed successfully with education,
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reassurance, iron supplementation if indicated, and
nonpharmacologic strategies. Pharmacologic therapies such
as clonazepam or carbidopa-levodopa may be considered
for severe symptoms.
End-stage renal disease — The management of RLS/WED in
patients with end-stage renal disease is similar to that in
patients with normal renal function. However, medication
doses may need to be adjusted, especially if the patient is
not yet receiving dialysis, as dopamine agonists and alpha-
2-delta ligands are all excreted by the kidneys. Careful
attention to iron status is especially important in this group..
REM-SLEEP BEHAVIOUR DISORDER
Most parasomnias are benign unwelcome phenomenon
observed in and around sleep that seldom present alarmingly.
It is a common observation that more often than not, they are
a cause of least concern both to patient and clinician. One such
sleep-related phenomenon is REM-sleep behaviour disorder
(RBD) that was first systematically defined 30 years back. It
is a kind of parasomnia characterized by dream enactment
behaviour (DEB) that emerges during rapid eye movement
sleep and may lead to injury or disturbance of sleep. Behaviours
include excessive abnormal and/or purposeful motor activities
such as vocalization and simple limb twitching to flailing
and punching of arms, sitting up, and kicking. Occasionally,
patients climb out of bed, something akin to sleep walking.
More complex and violent behaviours may occur rarely or
many a times during the same night, most action occurring
in bed. Not keeping with their waking personality, the
vocalizations may be loud and full of abuse and obscenities.
The routine REM-sleep atonia is typically absent. It manifests
as sustained muscle activity or transient phasic muscle
twitches in either the chin or limb electromyography (EMG) on
polysomnography (PSG). Most cases arise after the age of 50.
Its usual presentation in a speciality clinic is like a 65-year old,
male whose partner expresses concern about some unusual
sleep behaviour or who had injured himself or assaulted his
partner during sleep while having vivid, action-filled dreams of
self-defence. The reported prevalence rates are 0.38%-0.5% in
general population and, probably higher (≥6%) in 70-90 year
olds. Even more interesting is the equally higher prevalence
of RBD in psychiatric population (5.8%). The early-onset
(<50y) variety (EORBD) has more atypical clinical presentation
showing female preponderance, less violent behaviour, may
occur early during the night, and may get out of bed more
frequently. There is preponderance of idiopathic cases and
more association is seen with narcolepsy, depression, anti-
depressants and parasomnia overlap disorder (POD).
Indian demographics regarding this illness are largely
unknown and the published evidence is limited to half a
dozen case reports, retrospective chart reviews, prospective
questionnaire-based study and a case control study. All
discuss RBD as part of PD except one (table 9).
The aetiology of RBD is still speculative. RBD may be either
primary idiopathic type (iRBD) or secondary (table 10) to
other disorders. It is unclear whether the idiopathic variety
is an independent entity or it is merely a precursor
‘cryptogenic’ prodromal syndrome anti-dating degenerative
brain disorders predominantly of α-synucleinopathy type
((Parkinson’s disease (PD), dementia of Lewybody(DLB),
Multiple system atrophy (MSA)). RBD patients are at higher
risk of having cognitive, motor and autonomic impairments
at baseline. It may be that spontaneous iRBD precede a
parkinsonian neurodegenerative illness by several decades
and thus have a prognostic and therapeutic relevance. The
risk of iRBD converting to parkinsonian disorder varies
between 40-80% over 5-15 years. There is now a growing
body of evidence that suggests that depression may also be
a preclinical marker of PD in iRBD cases and anti-depressants
simply unmask the underlying pathology. Following are the
environmental and behavioural risk factors associated with
RBD (in common with PD):
1. traumatic brain injury,
2. farming,
3. pesticide exposure, and
4. low education.

Table 9: Evidence base on RBD‑ Indian studies

Authors Year Title Type of study Journal
Vibha D et al. 2011 RBD in Parkinson’s disease: a clinical case control study from India Case control Clinical Neurology
&Neurosurgerry
Gupta R et al. 2013 REM sleep behavior disorder in Parkinson’s disease: A case from India Case report Journal of Neurosciences
confirmed with polysomnographic data in Rural Practice
Mahale R et al. 2014 Rapid eye movement sleep behaviour disorder in young ‑ and older ‑ onset Cross‑sectional Sleep Medicine
Parkinson disease ‑ a questionnaire‑based study
Yadav R et al. 2015 Is palmomental reflex an important clinical marker of REM sleep behaviour Cross‑sectional Movement Disorders
disorder in patients with Parkinson’s disease?
Gupta S et al. 2015 Idiopathic REM Sleep Behavior Disorder: A Report on Two Cases with Case report Indian journal of
Contrasting Features Psychological Medicine
Siddiqui M M et al. 2015 Detection of rapid eye movement behaviour disorder using short time frequency Experimental Biomedical Research
analysis of PSD approach applied on EEG signal (ROC‑LOC)
Prashanth R et al. 2014 Parkinson’s disease detection using olfactory loss and REM sleep disorder Experimental Engineering in Medicine
features and Biology Society

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Table 10: Secondary causes of RBD
Multiple System Atrophy Brain tumours
Dementia of Lewy Body Multiple sclerosis
Parkinson’s disease (PD) Guillain‑Barre syndrome
Mild Cognitive Impairment Stroke
Spinocerebellar Ataxia 3 Narcolepsy
Guadeloupean parkinsonism Obstructive sleep apnoea (Pseudo‑RBD)
Alzheimer’s disease Medications (anti‑depressants, beta‑blockers)
Progressive supranuclear Substance withdrawal (alcohol, barbiturate)
palsy
Huntington’s disease Limbic Encephalitis
Frontotemporal dementia
Studies on animal model suggest involvement of brainstem
REM-sleep regulating nuclei, namely dorsal pontinesublateral
dorsal nucleus and/or magnocellular reticular formation.
The role of several genetic links is under study at present.
The risk of sleep-related injury (SRI) is markedly increased in
RBD cases and their bed partners (33%-95%). DEB vary from
harmless actions like knitting, singing, etc., to injurious ones
and common injuries include bruises, abrasions, lacerations,
fractures and dislocations, attempt at strangulation of partner
and occasionally, subdural hematomas. Lifetime incidence of
head injury is around 20%. Risk factors for SRI are:
• Idiopathic RBD
• Severe limb movements during DEB
• Dream recall
• Falling out of bed during DEB
It is to be noted that as against the common wisdom,
DEB frequency has not been found to be associated
with the frequency and severity of SRI. Cases of PD-
RBD are less likely to injure themselves compared to
idiopathic RBD and injuries and falls are more common
in PD-RBD than PD alone. RBD is a progressive disorder
and spontaneous remissions are witnessed very seldom.
There can be a gradual reduction of RBD symptoms over
the years in approximately 30% of the patients and they
may remit spontaneously in 14-30% of RBD-PD patients
per year. These data are probably reflective of progressive
neurodegeneration. DEB is absent in up to 30% of reported
cases of RBD.
Assessment and evaluation
Despite the presence of RBD in a higher number of patients
with PD, less than 1% complain about it at the time of
presentation. The reasons can be
• RBD being considered not severe enough or infrequent
to consult a physician
• Symptoms being perceived not worthy of discussion
• Unaware of their presence
• Waiting for them to resolve with time
• Feel shy to discuss.
Even if the above hiccups get surmounted, the required
support may still elude the patient either because the
S130
physician is unaware of RBD or the case may be misdiagnosed
a more common ailment such as epilepsy or sleep-walking.
Thus, an elaborate history with direct questions to
confirm the presence or absence of the symptoms of some
parasomnia is a must [Figure 4].
In RBD, a careful interviewing of bed-/room-partner will help
in eliciting of a history of brief recurrent DEB that occur
chiefly in the latter half of the night with patient confined
to bed distinguishing it from non-REM sleep parasomnias
that predominantly occur during first half without any dream
mentation. Two major classificatory systems define the
criteria for RBD diagnosis- International classification of sleep
disorders- third edition (ICSD-3) criteria and DSM-5 (Table
11 & 12). The DSM-5 now classifies RBD as an independent
disorder. ICD-10 is yet to come up with its own criteria of RBD
though ICD-10 CM does include RBD (G47.52) as a billable
code for the purpose of reimbursement claims in America.
There are several disorders that can present in a fashion similar
to RBDs that one needs to rule out. It should be also kept in
mind that these conditions may co-exist with RBD (Table 13).
On such example is POD, a younger-onset variant of RBD.
A baseline neurological examination (NE) that involves
specific evaluation of cognition and screening for
extrapyramidal symptoms should be done once a diagnosis
of RBD is established (Table 14). RBD precedes parkinsonian
neurodegenerative disorders and is fairly prevalent (50-90%) in
α-synuclein disorders, while in rest of the neurodegenerative
disorders RBD follows (except spinocerebellar ataxia 3) other
neurological deficits and is uncommon.
Following investigations will aid to the diagnosis of RBD:
Specific
• PSG with time-synchronized video (vPSG) is the single
most important investigation.
• Electro-oculogram (EOG) monitoring
• EMG with multiple channels for chin, bilateral extensor
digitorum, and tibialis anterior muscles.
• Electrocardiogram (ECG)
• Nasal air flow
• Arterial blood oxygen saturation.
The revised scoring of PSG features of RBD has been detailed
in AASM Manual for the Scoring of Sleep and Associated
Events: Rules, Terminology and Technical Specifications,
Version 2.2. RBD is the only parasomnia that requires vPSG
for confirmation of diagnosis.
Others
To aid in diagnosis or monitor:
• Routine lab investigations
• Neuroimaging – currently used as research tools to
identify pre-clinical disease markers
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• Transcranialsonography (TCS)- substantianigra (SN) Scales/Questionnaires/Inventories

echogenicity, a disease marker
• Positron-emission tomography (PET)- to assess
severity and extent of neurodegeneration
• Single photon emission computed tomography
(SPECT)- to study the SN dopaminergic neuronal
status
• Post-mortem brain autopsy
Table 11: ICSD‑3 criteria
Criteria A‑D must be met
Repeated episodes of sleep related vocalization and/or complex motor
behaviours*
These behaviours are documented by PSG to occur during REM sleep
or, based on clinical history of dream enactment, are presumed to occur
during REM sleep
PSG recording demonstrates REM sleep without atonia (RWA)**
The disturbance is not explained more clearly by another sleep disorder,
mental disorder, medication, or substance use
On occasion, there may be patients with a typical clinical history of RBD
with DEB, who also exhibit typical RBD behaviours during vPSG, but do
not demonstrate sufficient RWA, based on the current evidence‑based data,
to satisfy the PSG criteria for diagnosing RBD. In such patients, RBD may
be provisionally diagnosed, based on clinical judgement. The same rule
applies when vPSG is not readily available.
*Dream enactment is not exclusive to RBD **In ‘Subclinical’ RBD, criteria C is
present in absence of dream enactment
Table 12: DSM‑5 criteria of RBD (327.42)
Recurrent episodes of arousal during sleep associated with vocalization
and/or complex motor behaviours
These behaviours arise during rapid eye movement (REM) sleep and
therefor usually occur more than 90 minutes after sleep onset, are more
frequent during the later portions of the sleep period, and uncommonly
occur during daytime naps.
Upon awakening from these episodes, the individual is completely awake,
alert, and not confused or disoriented.
Either of the following:
RWA on PSG
A history suggestive of RBD and an established synucleinopathy
diagnosis (e.g., parkinson’s disease, multisystem atrophy)
The behaviours that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning (which may
include injury to self or bed partner)
The disturbance is not attributable to the physiological effects of a
substance (e.g., a drug of abuse, a medication) or another medical
condition
Coexisting mental and medical disorders do not explain the episodes
Since access to vPSG is limited, clinical interview and
questionnaires may come in handy in early screening of RBD
cases and related morbidities. Number of tools are available
for this purpose and to choose the right tool will depend on
whether it is required for rapid screening of RBD in general
population, or in specific specialized population such as
psychiatric cases and patients suspected of neurodegenerative
illness, or to monitor progress of illness or effects of some
intervention, and who is the source of information. It is to be
noted that despite their ease of availability and applicability,
screening tools are not a replacement for vPSG. RBD scales
help us point out probable RBD cases and thus to plan out
RBD specific assessment and targeted intervention services
without causing a resource crunch.
For RBD screening
1. RBD Questionnaire-Hong Kong (RBDQ-HK)
2. RBD screening questionnaire (RBDSQ),
3. Mayo sleep questionnaire (MSQ),
4. RBD1 questionnaire,
5. Innsbruk RBD inventory,
For RBD severity
1. RBD severity index (in Japanese),
2. Minnesota parasomnia injury scale,
For sleep
1. Epsworth sleepiness scale,
2. Pittsburgh sleep quality index
For baseline cognitive screening
1. Modified mini-mental state examination
2. Montreal cognitive assessment
For parkinsonian features
1. Unified Parkinson disease rating scale
Formulation of a treatment plan & Choice of treatment
setting [Figure 4]
Any treatment plan concerning RBD will involve reduction of
DEB and prevention of injury, irrespective of frequency and

Table 13: Differential diagnosis of RBD

Disorders of arousal Others
Primary Secondary
Sleep terror Periodic limb movement disorder Physiologic hallucinations of sleep
Sleep walking Nocturnal seizures (e.g., frontal lobe epilepsy) Dissociative/conversion disorder
Sleep talking Gastroesophageal reflux disease Malingering
Confusional arousals Obstructive sleep apnoea Domestic violence
Post‑traumatic stress disorder
Vertigo
Absence seizures
Epilepsy in mentally retarded
Other seizure disorders (e.g., juvenile myoclonic
epilepsy, benign epilepsy of childhood)
Hereditary quivering chin syndrome

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Table 14: Neurological history and examination‑salient severity of DEB. The choice of treatment setting will be largely
features determined by the presenting complaints. Hospitalization
Triad of impending Explore for Early bradykinesia Subtle signs on NE: may be required for assessment of RBD, treatment of SRI
neurodegeneration: • Difficulty in turning over • Affect and/or current medical condition. SRIs in RBD can be life-
• RBD with chronic in bed • Voice volume
threatening and may have medico-legal consequences.
unexplained • Slowing of eating or dressing • Speed of articulation
• Hyposmia • Above difficulties • Blink rate
• Constipation unilateral (u/l)/bilateral • Motor tone While formulating a treatment plan of RBD following should
• If, Impaired colour (u/l significant of • Cogwheel rigidity be included:
identification, rapid parkinson’s disease) • Gait testing: stride
conversion to PD • Change of hand‑writing length, arm swing,
• Non-pharmacological measures
•*psychiatric disorders • Lowering of speech volume number of steps to • Safety measures
(depression) may also • Whether ever felt feet stuck turn, freezing • Removal or minimization of aggravating factors
be a predating factor to the floor • Postural instability
• Counselling of patient and care-givers

No
Adequate opportunity for sleep Rules out insomnia

No
Difficulty in maintaining sleep Evaluate for other sleep disorders

No
Evaluate for OSA &/or other sleep
Abnormal behavioural activity during night sleep
disorders

Clinical features of a parasomnia

No
Assess for NREM parasomnias/ other
Suggestive of RBD
causes of insomnia

vPSG fulfilling diagnostic criteria

Assess for type of RBD

No
Assess & manage causes of secondary
iRBD RBD

Environmental & life style modifications

No
Try different drug &/or non-
Response
pharmacological measures

Yes
Continue indefinitely Response

No

Regular follow-up and monitoring for

appearance of any neurodegenerative disorder Review diagnosis

Figure 4: Diagnosis and management of REM-sleep behaviour disorder

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Table 15: Drugs used in treatment of RBD

Molecule t1/2 (hr) Dose (mg/d) Formulations Adverse effects
Benzodiazepines
Alprazolam 12‑15 1‑3 Tablet/extended Sedation, fatigue, dizziness, ataxia, confusion,
release/solution forgetfulness (B)
Clonazepam 30‑40 0.5‑2 Tablet (B) + blood dyscrasias, grand-mal seizures
Temazepam 8‑15 7.5‑30 Capsules (B) + hallucinations, mania, hypotension, hypersalivation
Triazolam 1.5‑5.5 0.125‑0.5 Tablet (B) + Anterograde amnesia, mania, dry mouth, hypersalivation
Non‑benzodiazepine
receptor agonist
Zopiclone 3.5‑6.5 7.5 Tablet Sedation, dizziness, ataxia, dose‑dependent amnesia,
hyperexcitability
Melatonin and
melatonin‑receptor
agonists
Melatonin 0.33‑0.83 (dose 3‑12 Tablet, capsule, Vivid dreams, nightmares, drowsiness, abdominal cramps,
& route cream, lozenges, headache, irritability, ↑depression, ↑risk of seizures in
dependent) intranasal spray children with severe neurological problems. RARE‑ ↓libido,
gynaecomastia, psychosis
Agomelatine 1‑2 25‑50 Tablet Nausea, dizziness, somnolence, hyperhidrosis. RARE‑ mania,
hepatitis
Ramelteon 2‑5 8 Tablet Sedation, dizziness, fatigue, headache
Anti‑depressants
Desipramine 24 50‑300 Tablet Blurred vision, constipation, urinary retention, increased
appetite, dry mouth, weight gain, sedation, sexual dysfunction.
RARE‑↑intraocular pressure, paralytic ileus, ↑QTc
Paroxetine 24 10‑40 Tablet‑IR & CR Sexual dysfunction, diarrhoea, constipation, insomnia,
sweating, tremors. RARE‑ hyponatremia, suicidality, mania,
bleeding
Pramipexole 8‑12 0.5‑1.5 Tablet Dizziness, Sleep attacks, somnolence, insomnia, nausea,
constipation, asthenia, peripheral oedema, impulse control
disorders, gambling, sexual urges, hallucinations & psychosis,
RARE‑ dyskinesias, rhabdomyolysis, peritoneal/pleural/
pulmonary fibrosis
Dopaminergic
L‑dopa 0.83‑1.5 250‑1250 Tablet, Agitation, delusions, hallucinations, confusion, tremors,
extended‑release, fainting; depression, blurring of vision, blepharospasm.
capsule RARE‑ hypertension, priapism, seizures, gastrointestinal
bleeding
Herbal
Yoku‑kan‑san/Yi‑Gan 1.72‑12.3 2.5‑7.5 Freeze‑dried granules Hypokalaemia (in old), drowsiness, tiredness, gastrointestinal
San (component upset. RARE‑ interstitial pneumonitis, dermatitis,
dependent) hepatotoxicity
Acetyl cholinesterase
inhibitors
Donepezil 70 5‑10 Tablet Nausea, diarrhoea, vomiting, ↓appetite, weight loss,
insomnia, abnormal dreams, muscle cramps. RARE‑ seizures,
syncope (B)
Rivastigmine 1‑2 6‑12 Capsule, liquid, (B) + headache, asthenia, sweating
transdermal
GABA agonist
Sodium Oxybate 0.5‑1 2500‑9000 Oral solution Swelling over face or extremities, weight gain, paraesthesias.
Anxiety, rash, perspiration, palpitation, tightness in chest,
seizures, coma.
Anti‑epileptic
Carbamazepine 12‑17 (repeated 400‑1200 Tablet, capsule, Sedation, dizziness, confusion, unsteadiness, headache,
doses) suspension nausea, vomiting, diarrhoea, rash. RARE‑ aplastic anaemia,
Anti‑psychotic
Clozapine 5‑16 N.A. Tablet ↑risk for diabetes/dyslipidaemias, ↑salivation, sweating,
sedation, constipation, weight gain. RARE‑ tardive dyskinesia,
agranulocytosis, seizures (dose‑dependent), neuroleptic
malignant syndrome, deep vein thrombosis and pulmonary
embolism, ↑risk of death and cerebrovascular events in elderly
patients with dementia‑related psychosis

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• Others
• Pharmacotherapy
Non-pharmacological meassures
The primary goal of RBD treatment is SRI prevention.
Among the non-pharmacologic measures, modification of
sleep environment should be initiated as the first step.
A. Environmental modification may include:
Patient safety. e.g.,
lowering of bed
putting a mattress on the floor alongside bed
sleeping on the floor mattress itself
shift bed/ bedroom to the lowest floor of the house
barricading with pillows around the bed
using a bed with padded rails
minimize furniture around the bed
maximize the distance from ungrilled windows
soft-pad the sharp edges of furniture around the house
remove fire-arms or knives from within reach
(preferably lock away)
safety locking of windows and doors
physical restraint. e.g., sleeping bags, padded belts,
padded waterbeds
Partner safety
Bed partner should sleep separate from the patient
till the problem symptoms of RBD are brought
under control with treatment.
It is a matter of investigation whether environmental
manipulation is enough in itself for the management of RBD
or it has only an adjunct role to pharmacotherapy.
B. Patient or caregiver should be asked to maintain a sleep diary
C. Avoid sleep deprivation- maintain adequate total sleep
time with a fixed waking time.
D. Avoid alcohol and/or other recreational drugs.
E. Treat co-morbid sleep disorders, if any.
F. Reassure and counsel patient and family about need
of treatment, regular follow-ups, and the possibility of
onset of a neurodegenerative disorder.
G. Review ongoing medication charts. Remove or reduce
the dose of aggravating agent wherever possible.
Antidepressants can trigger RBD or expose RBD in up
to 6% cases of depression. Tapering off might result
in symptom reduction but not complete remission
in such cases. Bupropion is the only anti-depressant
not reported to be associated with RBD till date.
Thus, it might be considered for use in those where
pharmacotherapy is indicated for depression.
Along with these measures, pharmacological treatment
should be instituted. As no large randomized double-blind
or head-to-head controlled trials are available till date
to assess efficacy of medications, the current treatment
guidelines are largely expert consensus, based on evidence
of large case series or small clinical trials.
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Pharmacological treatment
The only REM-sleep parasomnia where pharmacotherapy is
clearly indicated is RBD. Many pharmacological agents have
been tried for this purpose, but there is marked variation
in their efficacy and there is lack of standardization of the
dose of medication and the duration of its continuation
(Table 15). Among all the medications utilized till date,
the most robust support is for clonazepam and melatonin.
A medication that improves sleep quality with minimum
day time effects and results in improvement of objective
measures of RBD such as RWA on PSG should be chosen.
Clonazepam
Recommended as first-line medication. The evidence
base is almost exclusively in terms of retrospective
case reports and case series in over 300 patients. Initial
response to low dose clonazepam (0.5-2mg) is seen in
upto 90% of patients but later tolerance and treatment
failures are reported. Because of its long half-life, it may
become a cause of concern if causing impaired alertness,
morning sedation and gait impairment in parkinsonian
disorders and elderly patients and can worsen concomitant
obstructive sleep apnoea (OSA). It vanquishes DEB but do
not re-establish REM sleep atonia. It helps markedly in
reduction of SRI, one study reporting a reduction from
80.8% pre-treatment events to 5.6% post-treatment levels.
Patients on clonazepam should be regularly monitored
for development of newer symptoms of dementia or gait
disorders. Clonazepam is metabolized by cytochrome p450
enzyme system (cyp2C19 & cyp3A4). Thus, the possibility
of drug-drug interactions should be kept in mind especially
in elderly population where polypharmacy is a rule rather
than exception.
Melatonin
The pineal gland secretion, melatonin when used
exogenously is said to be effective in RBD in few case reports,
case series and a small randomized controlled trial of eight
patients. Recent studies find melatonin as efficacious as
clonazepam in RBD with a better adverse effect profile
and re-establishment of REM atonia especially in those
with dementia or sleep apnoea. Efficacy is not known in
cases where RBD co-exists with both PD/dementia and
depression that requires treatment with anti-depressants.
Most patients respond to 3mg dose with minimal or no side
effects. The mechanism of action of melatonin in RBD is not
known, though calmodulin antagonism is suggested as a
potential mechanism and the effects probably go beyond
simple hypnosis.
Others
In cases where clonazepam and melatonin are not
indicated or are refractory to these medications, other
medications may be tried. But so far, the evidence in
their favour is inadequate or at times, contradictory.
e.g., there are just two case reports of successful RBD
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treatment with sodium oxybate. Acetylcholinesterase
inhibitors may be instituted in patients with dementia or
synuleinopathies.
Among all the tried medications, the only preparation that
is claimed to have some neuroprotective effects in in-vitro
and in-vivo animal studies is Yi-Gan San/Yoku-kan san. It
is a Chinese/ Japanese traditional kampo preparation that
consists of seven different herbs- Japanese Angelica root
(3g), Atractylodeslancea rhizome (4g), Bupleurum root (2g),
Poriasclerotium (4g), Glycyrrhiza root (1.5g), Cnidium rhizome
(3g), and Uncaria hook (3g). Its neuropharmacodynamic
actions include serotonergic, glutamatergic, cholinergic,
dopaminergic, adrenergic, GABAergic along with
anti-inflammatory, anti-stress, neuroplasticity, and
neuroprotective effects. It is through these mechanisms
it is supposed to exert its effects in its primary indication
for behavioural and psychological symptoms of dementia
including alzheimer’s disease, dementia of Lewy body, and
PD. There is one case report of successful management of
three RBD patients with Yi-Gan San.
Other Pharmacological Treatment Modalities
It is very ironic that currently there are no cognitive or
cognitive-behaviour therapies available for REM-sleep
“behaviour” disorder probably highlighting the
‘non-functional’ organic nature of the disorder. Two
therapies- one behaviour and one somatic- does require a
mention though.
Bed Alarm Relying on the brain’s ability to process complex
auditory stimuli during REM sleep similar to wake state and
low arousal threshold for external stimulus Howell et al. at
university of Minnesota developed a pressurized bed alarm
customized with a pacifying pre-recorded message in a
familiar person’s reassuring voice to calm down the patient at
the onset of dream enactment behaviour. This prevents bed-
exiting and averts potential injuries. It can be used in patients
who are refractory to pharmacotherapy or do not tolerate it.
Deep brain stimulation of subthalamic nucleus is
ineffective in RBD though it does improve the subjective
sleep quality.
Management as per different phases of illness & when to
stop
RBD is a progressive neurological disorder. Though
clonazepam is highly effective and works in almost 70-90%
of the cases, relapse rates are high on discontinuation so
pharmacologic treatment should be continued indefinitely.
Regular monitoring to assess risk for neurodegenerative
disorders should be taken up keeping in mind the strong
relationship of RBD as a prodrome of such illnesses.
At present, there are no treatment strategies available to
prevent or delay the development of PD in iRBD cases.
Indian J Psychiatry 59 (Supplement 1), January 2017
It should be noted that most patients who ultimately
developed neurodegenerative illness were on clonazepam
indicating clonazepam’s ineffectiveness as a preventive
agent. It is recommended that an annual neurological
examination should be done for the earliest detection and
management of PD.
Special populations
The basic tenets of diagnosis, assessment and management
of medicine are equally applicable to the special populations
of RBD. The following few things should be kept in mind
while dealing with them:
Children
Assessment of children will require a careful approach
depending on their ability to communicate which can be
limited given their age or co-morbidity. Idiopathic RBD in
this population is rare and is usually seen in context with
narcolepsy, epilepsy, brain tumours, or, medication effects.
Elderly
After the onset of idiopathic RBD almost half of the patients will
develop a parkinsonian disorder within a decade, and nearly
80-90% will develop some neurodegenerative disorder in their
lifetimes. Therefore, middle-aged or elderly people presenting
with RBD symptoms should be counselled and monitored
about these future possibilities. An opportunity to enrol them
in any ongoing research clinical drug trials for developing and
testing disease-modifying drugs can also be explored.
Women
RBD is infrequently reported in females. This may be
because firstly, they might be having less injurious and
less dramatic behaviours during dream enactment; and
secondly, they may outlive their partner (gender difference
in life expectancy) thus having less likelihood of coming
to the notice of family members and receive the required
medical attention. All medications require caution for use
during pregnancy and lactation and should be taken only
under expert guidance.
The paramount importance of recognizing RBD as a
treatable parasomnia lies in the fact that it can prevent
serious life-threatening injuries. Psychiatrists should
actively screen for the presence of RBD as patients usually
do not come forward to report these symptoms for a
variety of reasons. The population of India grew at 17.7%
between 2001-11. During the same period there was a
quantum jump in the population of those above 60 years- a
staggering 35.5%. With an all-time high elderly population
of 8.6%, it is high time we brace-up for the identification of
RBD and appreciate its importance as a pre-clinical marker
of neurodegenerative illnesses. The success of any future
neuroprotective and preventive interventions will, thus,
rely on early and reliable identification of illness in its
nascent stage.
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Table 16: Symptoms of Obstructive sleep apnoea (OSA) cerebrovascular disorders, diabetes mellitus, pulmonary
Somatic symptoms Cognitive and Behavioural symptoms hypertension, arrhythmias, systemic hypertension,
Daytime sleepiness Decreased concentration memory disturbances, cognitive dysfunction and sexual
Fatigue Memory loss problems.
Irritability Decreased libido
Snoring Learning difficulties In addition, psychiatric disorders and OSA are also
Gasping/choking at night Impaired cognitive functioning
Morning headaches Personality changes
frequently comorbid, especially depression.Mood
Non-refreshing sleep Depression disturbance may represent a consequence of sleep apnoea.
Nocturia Anxiety Psychiatric disorders associated with weight gain may
also contribute to and promote the development of sleep
apneas. Medications with depressent effect on CNS can
Table 17: Medical history to be taken in patients
worsen or exacerbate the symptoms of OSA.Patients with
with OSA
sleep apnea often have fregmatned sleep and thus they may
Depression
Sedatives
have daytime symptoms of poor quality sleep e.g., fatigue,
Parkinsonism lethary, poor appetite, poor concentration, memory lapses,
Narcolepsy headache, distressed mood that may be mistaken for
Restless leg syndrome/periodic limb movement disorder depression. Fregmented sleep often presents as multiple
Hypothyroidism
somatic symptoms during the daytime suggesting the
β‑blockers
Idiopathic hypersomnolence diagnosis of somatoform disorder.
Excess alcohol
Previous head injury The symptoms are the direct consequences of OSA and
DystrophicaMyotonica occur due to the repetitive collapse of upper air ways.
Stimulants (caffeine, theophyllines, amphetamines)
Thin and lean individuals with significant apnoea are likely
OBSTRUCTIVE SLEEP APNOEA (OSA) to show upper airway abnormalities. These include, e.g.,
hypertrophic tonsils and adenoids, a low-set palate or
Sleep apnoea is charcaterized by recurrent pauses (at least palatal webbing, a large uvula, a large tongue or a small
5/hour) in breath, each lasting at least 10 seconds and is mandible.
important for the Psychiatric practice as it can mimic or
exacerbate symptoms of psychiatric disorders such as Risk factors, Screening, Examination and Diagnosis of OSA
depression, anxiety and panic disorder. The prevalence of OSA is higher in patients who have a
combination of the following risk factors: obesity, neck
Three types of apnoeas have been described in literature. larger than 17 inches for men or 16 inches for women,
In obstructive sleep apnoea (OSA), cessation of breathing male gender, middle age, large tonsils, or recessed chin.
occurs despite persistent respiratory efforts. In central Besides anatomical factors, physiological factors that
apnoea, there is no respiratory effort. Mixed apnoea has influence the tone of the upper airway muslces play
initial part similar to central apnea but in the later part, equally important role in generation of OSA. It is prudent
effort to breath is seen with absence of airflow throughout to screen all patents who are at risk since untreated OSA
the period. Excessive daytime sleepiness, one of the major is an independent risk factor for mortality. In addition,
symptoms of OSA is seen in one-third of the patients and information regrading conditions as described in Table 17
many report mid-nocturnal awakenings due to chocking must be gathered.
which may be mistaken for panic. On the other hand, central
sleep apnea has subtle clinical manifestations and often Physical Examination
these patients present with chronic non-restorative sleep. Examination is very important to exclude other causes for
the patient’s symptoms mentioned below:
Obstructive sleep apnoea (OSA) is a common disorder
with an estimated prevalence in the general population of Following points should be kept in mind during physical
2–5% (Table 16). Apnoea during sleep leads to decrease in examination
blood oxygen level which leads to disturbance in sleep and
frequent arousals. Sleep apnoea severity is assessed with • Weight and height should be documented.
apnoea-hypopnoea index (AHI), which is the number of
apnoeas and hypopnoeas per hour of sleep. • Mandibular and tongue abnormality.
• Assessment of Nasopharyngeal abnormality.
Obesity is a major risk factor for OSA. Untreated OSA leads
to significant clinical problems including cardiovascular and • Measurement of Blood Pressure.

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Gupta, et al.: CPGs for sleep disorders
• Perform routine respiratory, cardiovascular and
neurological examination to detect any coexisting disease.
Diagnosis
Certain questionnaires e.g., STOP-Bang, Berlin Questionnaire
have been developed to screen the OSA. However, the gold
standard for the diagnosis of OSA is polysomnography.
Ideally, in-lab attended video-synchronized full
polysomnography (level 1) is indicated for the diagnosis of
OSA, however, among high risk cases, limited channel level
3 polysomnography may also be used. This is also known as
Home Sleep testing.
Treatment
Depending upon the severity the various treatment options
is most appropriate for the management of OSA.
Treatment options can be broadly divided into:
1. Patient education
2. Behavioural interventions
3. Non-surgical options
4. Surgical options.
5. Treatment for comorbidities.
Patient Education
Patients and their attendants should be educated about the
pathophysiology, risk factors, clinical consequences and the
treatment of OSA.
Education should include behavioural modification like
weight loss, sleep position, alcohol avoidance, risk factor
modification, and medication effects.
Behavioural Interventions
Lifestyle changes can be very effective in mitigating the
symptoms of sleep apnoea. However, large control trials are
not available in this regard.
1. Weight loss is most important in all those who are
overweight. Weight reduction improves symptoms in
OSA
2. Exercise
3. Avoidance/Reduction of smoking and alcohol is
beneficial.
4. Sedatives or sleeping tablets should be avoided.
5. Snorers should be discouraged from sleeping on their
backs.
Non-Surgical Options
1. Positive Air Pressure (CPAP). This is the “gold standard”
treatment for OSA. Optimal pressure of the PAP should
be titrated as per the standard guidelines so as to
ameliorate all kinds of sleep related breathing events-
apnea/hypopnea, RERA and snoring. Automatic PAP has
limited application in these cases.
2. Oral Appliances: These are effective only in mild to
moderate severe cases of OSA.
Indian J Psychiatry 59 (Supplement 1), January 2017
I. Mandibular Advancement Splints (MAS). This works
by moving the mandible forward along with the
tongue and increasing the caliber of upper airway.
Surgical Options
The treatment of choice for moderate to severe OSAS is
continuous positive airway pressure (CPAP) devices , but
patient adherence to these devices has been a limiting factor.
In ‘selected cases’, surgical treatment on the upper airway
(UA) or on the facial skeleton may be beneficial in alleviating
this disease or improving the use of CPAP. Following surgical
procedures can be beneficial to patients with OSA.
Any of the single staged procedure has not been found
effective in management of OSA in large controlled trials.
Patient should be educated regarding possible recurrence
of OSA after 1-2 years of surgery, especially when it is done
on the soft tissues.
Treatment for comorbidities
Hypothyroidism, depression, etc, are more prevalent
.Obstructive sleep apnea (OSA) and hypothyroidism are
relatively common disorders that have similar clinical
features and are thought to be causally linked. The
mechanisms proposed to explain how hypothyroidism
might cause OSA include mucoprotein deposition in the
upper airway, decreased neural output to the upper airway
musculature, obesity, and abnormalities in ventilatory
control.
Treatment of hypothyroidism in the presence of sleep apnea
is potentially hazardous and may lead to cardiovascular
complications. Management by a combination of  Nasal
continuous positive airways pressure(CPAP) and low-dose
thyroxine is helpful in this situation.
OSA patients may have comorbid depression or any other
psychiatric illness. In such cases bothe the disorders must
be adequately and optimally treated.
Obstructive sleep apnea (OSA) leads to frequent arousals,
which are characterized by fragmented sleep. Persistent
sleep loss can lead to depressive symptoms. Patients may
be treated for depression, but if the underlying symptoms
are caused by OSA and the apnoea is not treated, depressive
symptoms can remain. We may be treating someone with
antidepressants when what we really should be doing is
treating their sleep disorder, which could in turn restore
their normal mood.
SUGGESTED READINGS
1. Sharma S, Trivedi JK. Guidelines for the treatment of Sleep disorders.
Available at www.indianjpsychiatry.org/cpg/cpg2006/cpg-mgmt_16.pdf.
Last accessed 10 Oct 2016
2. Sharma SK, Kumpawat S, Banga A, Goel A. Prevalence and risk factors
of obstructive sleep apnea syndrome in a population of Delhi, India. Chest
S137
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Gupta, et al.: CPGs for sleep disorders
2006;130:149–56.
3. Rangarajan S, Rangarajan S, D’Souza GA. Restless legs syndrome in an
Indian urban population. Sleep Med 2007;9:88–93.
4. American Academy of Sleep Medicine. International Classification of Sleep
Disorders. 3rd ed. Darian, IL: American Academy of Sleep Medicine; 2014.
5. Gupta R, Zalai D, Spence DW, BaHammam AS, Ramasubramanian
C, Monti JM, et al. When insomnia is not just insomnia: the deeper
correlates of disturbed sleep with reference to DSM-5. Asian J Psychiatr
2014;12:23–30.
6. Gupta R. Presleep thoughts and dysfunctional beliefs in subjects of
insomnia with or without depression: Implications for cognitive behavior
therapy for insomnia in Indian context. Indian J Psychiatry 2016;58:77–82.
7. Dhyani M, Rajput R, Gupta R. Hindi translation and validation of
dysfunctional beliefs and attitudes about sleep (DBAS - 16). Ind Psychiatry
J 2013;22:80–5.
8. Morin CM, Vallières A, Ivers H. Dysfunctional beliefs and attitudes
about sleep (DBAS): validation of a brief version (DBAS-16). Sleep
2007;30:1547–54.
9. Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index:
psychometric indicators to detect insomnia cases and evaluate treatment
response. Sleep 2011;34:601–8.
10. Lahan V, Gupta R. Translation and validation of the insomnia severity
index in hindi language. Indian J Psychol Med 2011;33:172–6.
11. Thompson W, Quay TAW, Rojas-Fernandez C, Farrell B, Bjerre LM,
Pringsheim T, et al. Atypical antipsychotics for insomnia: a systematic
review. Sleep Med 2016;22:13–7.
12. Laudon M, Frydman-Marom A. Therapeutic effects of melatonin receptor
agonists on sleep and comorbid disorders. Int J Mol Sci 2014;15:15924–50.
13. Mitchell MD, Gehrman P, Perlis M, Umscheid CA. Comparative
effectiveness of cognitive behavioral therapy for insomnia: a systematic
review. BMC Fam Pract 2012;13:40.
14. Morin CM, Edinger JD, Krystal AD, Buysse DJ, Beaulieu-Bonneau S, Ivers H.
Sequential psychological and pharmacological therapies for comorbid and
primary insomnia: study protocol for a randomized controlled trial. Trials
S138
2016;17:118.
15. Allen RP, Burchell BJ, MacDonald B, Hening WA, Earley CJ. Validation
of the self-completed Cambridge-Hopkins questionnaire (CH-RLSq) for
ascertainment of restless legs syndrome (RLS) in a population survey.
Sleep Med 2009;10:1097-100.  
16.  Gupta R, Allan RP, Pundeer A, Das S, Dhyani M, Geol D. Hindi translation
and validation of Cambridge-Hopkins diagnostic questionnaire for RLS
(CHRLSq).Annals of Indian Academy Of Neurology . 2015 Jul ; 18(3): 303
17. Scholz H, Trenkwalder C, Kohnen R, et al. Dopamine agonists for restless
legs syndrome. Cochrane Database Syst Rev 2011; :CD006009.
18. Wilt TJ, MacDonald R, Ouellette J, et al. Pharmacologic therapy for
primary restless legs syndrome: a systematic review and meta-analysis.
JAMA Intern Med 2013; 173:496.
19. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders. 5th ed. Arlington (VA): American Psychiatric Association;
2013.
20. Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR,
Chowdhuri S, et al. Standards of Practice Committee, American Academy
of Sleep Medicine. Best practice guide for the treatment of REM sleep
behavior disorder (RBD). J Clin Sleep Med 2010;6:85-95.
21. Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Marcus CL,
et al. The AASM Manual for the Scoring of Sleep and Associated Events:
Rules, Terminology and Technical Specifications, Version 2.2. Darien (IL):
American Academy of Sleep Medicine; 2015.
22. Johns MW. A new method for measuring daytime sleepiness: the Epworth
sleepiness scale. Sleep. 1991;14(6):540–545.
23. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen
patients for obstructive sleep apnea. Anesthesiology. 2008;108:812.
24. Oğuztürk Ö, Ekici M, Çimen D, Ekici A, Senturk E. Attention
deficit/hyperactivity disorder in adults with sleep apnea. J ClinPsychol Med
Settings. 2013;20(2):234–239.
Indian J Psychiatry 59 (Supplement 1), January 2017
[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]

ERRATUM

Erratum: Clinical practice guidelines for the management of depression

In the article titled “Clinical Practice Guidelines for the management of Depressionia” published in pages 34-50, supplement
issue 1, vol. 59 of Indian Journal of Psychiatry[1], the information in the section “Participants of expert group on CPG for
Depression” is written incorrectly. The correct information in the section should read as “Participants of expert group on
CPG for Depression: I.D Gupta, Navendu Gaur, Tushar Jagawat, Anita Gautam N.N. Raju, S.C. Tiwari, Roop Sidhana, T.S.S.
Rao, K.K Mishra, Gautam Saha”

REFERENCE

1. Gautam S, Jain A, Gautam M, Vahia VN, Grover S. Clinical Practice Guidelines for the management of Depression. Indian J Psychiatry 2017;59:34-50.

DOI: 10.4103/0019-5545.211279

258 © 2017 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow

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CASE REPORT

Use of modified bilateral electroconvulsive therapy during pregnancy:

A case series
Sandeep Grover, Pooja Sikka1, Shiv Sajan Saini2, Neeru Sahni3, Subho Chakrabarti, Devakshi Dua, Anisha
Aggarwal, Anita Thakur, Shallu Dhiman, Amal Jolly, Swapnajeet Sahoo, Aseem Mehra, Aditya Somani
Departments of Psychiatry, 1Obstertrics and Gynaecology, 2Neonatology and 3Anaesthesia and Intensive Care, Postgraduate
Institute of Medical Education and Research, Chandigarh, India

ABSTRACT

There is limited literature on the use of electroconvulsive therapy (ECT) during pregnancy. ECT is considered as a
treatment of last resort during pregnancy. In this case series, we present the data of five patients who were administered
ECT during pregnancy. The use of ECT required multidisciplinary approach involving psychiatrist, gynecologist,
anesthetist and neonatologist. Two patients received ECT during the second trimester and three patients received ECT
during the third trimester. In all the patients, ECT was administered by placing the patients in the left lateral position,
glycopyrrolate was used for premedication, thiopentone was used for induction, and succinylcholine was used for
muscle relaxation. Patients who were administered ECT close to the full‑term were given injection betamethasone
12 mg intramuscularly on two consecutive days before starting of first ECT to promote fetal lung maturity. In all the five
cases, no adverse maternal and fetal outcomes were encountered except for possible precipitation of labor in one case.

Key words: Effectiveness, electroconvulsive therapy, pregnancy, safety

INTRODUCTION available on the use of ECT in these special populations, the

Electroconvulsive therapy  (ECT) is possibly the most
controversial psychiatric treatment, since its being in use.
However, it is possibly the only treatment in psychiatry
which has survived and has evolved over the last eight
decades or so and it still has its place in the management of
various severe mental disorders.
Because of the associated controversies, ECT is judiciously
used in special population, i.e., children and adolescents,
elderly and pregnant women. Although some data are
Address for correspondence: Dr. Sandeep Grover,
Department of Psychiatry, Postgraduate Institute of Medical
Education and Research, Chandigarh ‑ 160 012, India.
E‑mail: drsandeepg2002@yahoo.com
Access this article online
Quick Response Code
Website:
www.indianjpsychiatry.org
data are limited, especially in pregnancy. In general, ECT
during pregnancy is considered as the treatment of the last
resort.
Historically, pregnancy was considered as a contraindication
for use of ECT. Interestingly in the first published report of
use of shock therapy in a pregnant woman, seizures were
induced using insulin or metrazol therapy in a case because
the pregnancy was misdiagnosed as uterine fibroid.[1] After
this, many authors have reported information on the use
of ECT in pregnancy. Most of the available data are in the
form of case reports or case series. Some of the authors
have reviewed the available literature on the use of ECT in
pregnancy.[2,3]
This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com

How to cite this article: Grover S, Sikka P, Saini SS, Sahni N,

DOI:
Chakrabarti S, Dua D, et al. Use of modified bilateral
electroconvulsive therapy during pregnancy: A case series.
10.4103/psychiatry.IndianJPsychiatry_50_17
Indian J Psychiatry 2017;59:487-92.

© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow 487

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Grover, et al.: ECT during pregnancy
Anderson and Reti[2] reviewed the available literature from
1942 to 2007 and reported that there were 57 publications
between 1942 and 2007, which included 339  patients.
However, in many of the reports, complete data were not
available for all the parameters. Data from this review
suggested that ECT was effective in at least 60% of cases, in
which it was used.
In a recent review, authors reported that data on the use of ECT
among pregnant women is available only for 169 patients, as
documented in 67 published reports.[3] The number of cases
included in this report was lower than the previous review,
possibly because of difference in the inclusion criteria of
the two reviews. Leiknes et al.[3] excluded reports which did
not provide clear evidence of the use of ECT in pregnancy.
Leiknes et al.[3] reported that two‑third (63%) of the reports
were published between 1970 and 2013 and one‑third (37%)
of the reports were published during 1942–1970. As per
the authors, the data emerged from all the continents of
the globe. The mean numbers of ECTs administered during
pregnancy were 9.4 (standard deviation [SD] 6.4). The age of
the patients who received ECT varied from 16.5 to 48 years
with a mean age of 28.9 (SD – 6.2) years. Both unilateral
and bilateral ECT has been used, with thiopentone being
the most commonly used anesthetic agent. During 1970–
2013, in about two‑third (63%) of cases ECT was used for
the management of depression/bipolar disorder, with or
without psychotic symptoms. However, during the years
1942–1970, in about half (54%) of the cases, ECT was used
for the management of schizophrenia and other diagnoses
such as obsessive‑compulsive disorder, generalized anxiety
with panic attacks, and neuroleptic malignant syndrome.
In this review, authors reported that in most of the cases
ECT was administered to primipara women. In terms of
trimester of pregnancy, in which ECT was started, data
were available for 72% of cases and for which information
was available, it was seen that ECT was administered during
the second trimester in about half of the cases  (53%).
Further, in this review, the authors reported that data on
fetus‑related outcome was missing for 12% of cases and
information on ECT parameters was limited. It is suggested
that more than one‑fourth  (29%) of the cases, use of ECT
was associated with fetus‑related adverse outcomes such
as fetal heart rate deceleration, uterine contractions,
premature labor, and cesarean section. In occasional cases,
the use of ECT in mothers was associated with status
epilepticus in fetus. In a small proportion of cases (7.1%),
use of ECT during pregnancy has been linked to mortality
of the fetus/newborn. In none of the reports, the use of ECT
was associated with maternal death.[3] Since the publication
of this review few more case studies has emerged in the
literature. A recent meta‑review[4] included data from four
systematic reviews[2,3,5,6] and brought out the strengths and
weaknesses of the available reviews. The authors concluded
that the review of Leiknes et  al.[3] was superior to other
reviews; however, the authors of meta‑review pointed out
488
that, Leiknes et al.[3] possibly over‑implicated ECT in terms
of adverse outcomes, whereas the data does not suggest
that ECT had a causal role in many of the adverse outcomes.
Due to ethical reasons, it is not possible to conduct
controlled trials in pregnant women. Hence, we have to
rely on the spontaneously reported data on the use of ECT
during pregnancy. The review by Leiknes et al.[3] could locate
only one report from India,[7] in which authors reported the
use of ECT in two patients. We too could not find any other
report from India. In this background, we present the data
five patients who received ECT during pregnancy.
CASE REPORTS
Case 1
A 32‑year‑old female with 28  weeks of pregnancy was
referred to psychiatry outpatient setting by her attending
gynecologist for not cooperating for clinical examination
and requesting for termination of pregnancy. On evaluation,
it was evident that the patient was suffering from recurrent
depressive disorder, current episode severe depression
without psychotic symptoms. She had been treated with
lithium, sertraline, and mirtazapine during the second
trimester of pregnancy, without much improvement. Due
to severe anxiety, she had been abusing clonazepam to
overcome her symptoms without much relief. Due to the
distress of her symptoms, she was very restless, would not eat
anything, would demand for the termination of pregnancy
and blame her’ to be born child’ for all her suffering. She
was admitted to the inpatient unit. Initial attempt to
rationalize pharmacotherapy was not beneficial. Following
this, she was offered ECT. Her pre‑ECT evaluation in the
form of hemogram, serum electrolytes, liver function test,
renal function test, electrocardiogram, and fasting blood
glucose levels did not reveal any abnormality. Her fundus
examination did not reveal any evidence of papilloedema.
She was started on ECT after the 29th  completed weeks.
She received six ECTs with which there was significant
improvement in her symptoms of depression  [Table  1].
Following the completion of ECT, she was started on
cognitive behavior therapy along with the continuation
of pharmacotherapy. At 35th week (i.e., after 3 weeks of
completion of ECT), she developed pregnancy‑induced
hypertension, following which she underwent a cesarean
section and delivered a healthy female child.
Case 2
A 25‑year‑old female, suffering from paranoid
schizophrenia, since the age of 15  years, was referred
by her treating gynecologists at 30th week, for not being
cooperative for examination, poor weight gain during
pregnancy, and refusal to eat. On examination, the patient
was found to have florid positive symptoms in the form
of bizarre delusions, persecutory delusions, hallucinatory
behavior, negative symptoms, poor self‑care, and poor oral
Indian Journal of Psychiatry Volume 59, Issue 4, October-December 2017
 Table 1: Details of electroconvulsive therapy of patients who received electroconvulsive therapy during pregnancy
Case‑1 Case‑2 Case‑3 Case‑4 Case‑5
Age of the patient 32 years 25 years 40 years 28 years 42 years
Primary diagnosis Recurrent depressive disorder, current Paranoid schizophrenia Undifferentiated Bipolar affective disorder, Recurrent depressive disorder,
episode severe depression without psychotic schizophrenia current episode mania with current episode severe
symptoms psychotic symptoms depression without psychotic
Hypothyroidism symptoms
Intentional self‑harm Hypertension
Benzodiazepine abuse
Indication for ECT Severe depression, Treatment resistant Poor oral intake, poor Uncooperative, unaware of Uncooperative, attempt to Severe depression, psychotic
depression, suicidal thoughts, poor oral fetal growth, poor care pregnancy, lack of concern harm the fetus, lack of concern symptoms, suicidal ideations,
intake, marked anxiety of self and pregnancy about pregnancy about pregnancy severe distress
Medications at the time Tablet lithium 900 mg/day Haloperidol 5-10 mg/day Olanzapine 20 mg/day Haloperidol 5-10 mg/day Tab mirtazapine 15-30 mg/day
of ECT Tablet mirtazapine 30-45 mg/day Cap venlafaxine 75-150 mg/day
Baseline severity of HDRS 35 PANSS: P 28, N 21, PANSS: P 14, N 28, G 46 YMRS 32 HDRS 28
psychopathology G 41
Number of pregnancy Primipara Primipara Second pregnancy G2 P1 L1 G2 P1 L1
Pre‑ECT fetal status Ultrasound showed: Healthy fetus, no Physical examination: Ultrasound abdomen: Ultrasound abdomen: Physical examination: Small
congenital anomalies, 1000 g, appropriate to Small for the gestational Single‑live fetus, no Single‑live fetus, no congenital for the gestational age, did
gestational age age, did not cooperate congenital anomalies anomalies, weight 1990 g not cooperate for ultrasound
for ultrasound abdomen abdomen
Interventions done Injection betamethasone 12 mg IM was Injection betamethasone None Injection betamethasone 12 mg None
before ECT given on 2 consecutive days to promote fetal 12 mg IM was given IM was given on 2 consecutive
lung maturity on 2 consecutive days days to promote fetal lung
Injection progesterone 250 mg was given to promote fetal lung maturity

Indian Journal of Psychiatry Volume 59, Issue 4, October-December 2017

half an hour before every ECT to promote maturity Injection progesterone 250 mg
uterine relaxation Injection progesterone was given half an hour before
250 mg was given half every ECT to promote uterine
an hour before every relaxation
ECT to promote uterine
relaxation
Grover, et al.: ECT during pregnancy

Week of pregnancy at 29 completed weeks 34+2 weeks 22 weeks 35 weeks+5 days 23 weeks

which ECT was started
Type of ECT Bilateral‑modified Bilateral‑modified Bilateral‑modified Bilateral‑modified Bilateral‑modified
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Place of administration Operation theater Operation theater Routine ECT suit Operation theater Operation theater
of ECT
Position in which ECT Left lateral position Left lateral position Left lateral position Left lateral position Left lateral position
was given
ECT medications Glycopyrrolate, thiopentone, succinylcholine Glycopyrrolate, Glycopyrrolate, thiopentone, Glycopyrrolate, thiopentone, Glycopyrrolate, thiopentone,
thiopentone, succinylcholine succinylcholine succinylcholine
succinylcholine
Total number of ECTs 6 13 7 8 6
Total number of ECTs 6 6 7 5 6
during pregnancy
Total number of ECTs 0 7 0 3 0
after delivery
Efficacy of ECT Reduction in HDRS: 65.7% Reduction in PANSS: Reduction in PANSS: 70% Reduction in YMRS: Reduction in HDRS:
65% 81.2% (achieved remission) 78.6% (achieved remission)

489
Contd...
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Grover, et al.: ECT during pregnancy

intake. She also refused that she was pregnant. Abdominal

Normal vaginal delivery at 38th

examination revealed small for gestational age fetus. She
was admitted to the inpatient unit, and initially, she was

ECTs – Electroconvulsive therapy; HDRS – Hamilton Depression Rating Scale; PANSS – Positive and Negative Symptom Scale; P – Positive symptoms; N – Negative symptoms; G – General psychopathology;
Baby healthy at 1.5 years
managed with tablet haloperidol, without much benefit. In
view of poor oral intake and positive symptoms, she was
considered for ECT. Pre‑ECT evaluation  (as done for the
above‑described patient) did not reveal any abnormality.
Case‑5

weeks
Following this, she was treated with ECT, and she
None

None
2650
received six ECTs during the antenatal period [Table 1].

8
9
With ECT, she showed significant improvement in
Normal vaginal delivery at 38th

her psychopathology, started accepting that she was

pregnant. About a day after the sixth ECT, she developed

Baby healthy at 1 month

uterine contractions; however, labor did not progress,
even after waiting for 36 h. Following this, she underwent
cesarean section and gave birth to a healthy female baby.
However, in the immediate postpartum, she had relapse of
symptoms, which led to reinstitution of ECT.
Case‑4

weeks
None

None
2196
8
9

Case 3
A 40‑year‑old female, presented with disorganized
behavior, formal thought disorder, delusion of persecution,
Normal vaginal delivery at

Baby healthy at 6 months

and poor self‑care. Routine ultrasound abdomen revealed

that she was pregnant with pregnancy of about 20 weeks
duration. The patient was unaware of pregnancy and did
not show any concern about pregnancy. In view of the
38th weeks
Table 1: Contd...

severe psychopathology, poor social support, history

Case‑3
None

None
2600

of poor compliance to medication and poor oral intake,

9
9

she was considered for ECT after thorough evaluation.

She received seven ECTs, along with the continuation of
nonprogression of labor

olanzapine. She showed marked improvement, remained

Baby healthy at 1 year
contractions after 6th

compliant with medications after the completion of ECT

at 37th week due to
Starting of uterine

Cesarean section

and gave birth to a healthy boy at full term by normal

vaginal delivery.
Case‑2

None
3040
ECT

Case 4
10
9

A 28‑year‑old female presented to emergency with bipolar

affective disorder, current episode mania with psychotic
symptoms along with pregnancy of 33  weeks. Initially,
she was managed with antipsychotics. However, her
Cesarean section at 35th week due to

symptoms continued unabated and required admission

pregnancy‑induced hypertension

to the psychiatric inpatient unit. She was very much

agitated, disruptive, and would threaten to harm her
Baby healthy at 10 months

YMRS – Young Mania Rating Scale; IM – Intramuscular

fetus. Following this, she was considered for ECT. She

received five ECTs during the antepartum period and
three additional ECTs during the postpartum period. She
developed spontaneous labor during the 38th  week and
delivered a male child.
Case‑1
None

None
2730

10

Case 5
9

A 42‑year‑old female presented during the second trimester

Long‑term outcome of

with severe depressive episode without psychotic symptoms.

complications for the

complications for the

Apgar score at 1 min
Apgar score at 5 min

The depressive episode did not respond to adequate trials of

Mode of delivery
Any ECT‑related

Any ECT related

Birth weight (g)

newborn/fetus

newborn/fetus

psychotropics and patient became suicidal. Following this,

she was admitted to the inpatient unit and managed with
mother

six ECTs, started during the 24th week of pregnancy, with

which she should significant improvement. She maintained

490 Indian Journal of Psychiatry Volume 59, Issue 4, October-December 2017

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Grover, et al.: ECT during pregnancy
well for later half of pregnancy and gave birth to a healthy
male baby at term.
All these patients were administered brief pulse, bilateral
modified ECT, two to three times per week, by using an
indigenously manufactured brief‑pulse, constant‑energy
machine  (Medicaid Systems, Chandigarh, India). For all
these patients, the frequency was fixed at 70 Hz, and the
pulse width was fixed at 1 s. Initial current stimulus varied
from 0.4 to 0.6 s with initial charge of 48–72 coulombs.
All patients received proton pump blockers to reduce the
chances of gastric reflux. Premedication for ECT involved
the use of glycopyrrolate  (0.2–0.3  mg), and induction
was done using thiopental sodium  (100–300  mg) and
succinylcholine was used for muscle relaxation. All patients
received intravenous fluid in the form of saline before and
during the ECT procedures. All the patients were properly
preoxygenated with 100% oxygen before administration
of stimulus. Seizure duration was estimated using cuff
method, and a motoric seizure lasting for at least 15 s was
considered as an indicator of an effective ECT. In three
of the five cases, in which ECT was used during the third
trimester, patients were given injection betamethasone
12  mg intramuscular on two consecutive days before
starting of the first ECT to promote fetal lung maturity.
Injection progesterone 250  mg was given 30 min before
every ECT to promote uterine relaxation. The three cases,
in which ECT was administered during the third trimester,
the procedures were done in the operation theater with
multidisciplinary teams involving psychiatrist, gynecologist,
anesthetist, and neonatologist. In all the cases, patients
were monitored for uterine contractions before and after
the ECTs. In all the cases, ECT was given by placing the
patients in the left lateral position. Patients were intubated
after the procedure as per the requirement.
DISCUSSION
Data on the use of ECT during pregnancy is limited, and
the available literature is marked by insufficient details in
terms of ECT procedure, pre‑ECT evaluations, ECT‑related
complications, etc., Hence, there is a need to expand the
literature. We could find only one report from India, which
included description of 2  cases, in which ECT was used
during 24–26  weeks of pregnancy. However, this report
mainly focused on anesthetic procedures and did not
provide much detail about other ECT details and psychiatric
status.[7]
In the current case series, five patients were safely given
ECT, without any adverse maternal and fetal outcomes.
The American Psychiatric Association Task Force on ECT[8]
recommends that ECT should be used when there is a need
for rapid and definitive response, risk of other treatments
outweighs the risks of ECT, poor medication response, good
response to ECT in one or more previous episodes of illness,
Indian Journal of Psychiatry Volume 59, Issue 4, October-December 2017
and patient’s preference. In the current case series, in all
the cases, ECT was considered because of need for rapid
and definitive response. Patients who received ECT during
the third trimester, had risk factors for poor fetal outcomes,
i.e., poor oral intake, poor weight gain during pregnancy,
threat to harm the fetus.
Available evidence suggests that in recent times
(1970–2013), ECT has mostly been used during pregnancy
to manage patients with Depression/Bipolar disorder, with
or without psychotic symptoms.[3] In our case series too,
2 out of the 5  patients were suffering from depressive
episodes, and one patient had mania with psychotic
symptoms. In all the patients, ECT was administered
by multidisciplinary teams comprising of psychiatrists,
gynecologist, anesthetist, and neonatologist. The
multidisciplinary approach helped in decision‑making,
and all the specialists facilitated the ECT treatment for
possible better fetal outcomes. Accordingly, it can be said
that centers providing perinatal psychiatric care must
form multidisciplinary teams to improve the outcome of
pregnancies in patients with mental illnesses.
During the ECT procedure, all the patients were oxygenated
properly, and premedication involved used of glycopyrrolate
because it is suggested to have lower placental transfer
rate when compared to atropine.[8] In general, most of
the previous reports are silent about the use of steroids
close to the term. In the present case series, we used
betamethasone on two consecutive days to promote fetal
lung maturity. This was done as a preparation for unwanted
outcome such as precipitation of labor. This possibly helped
in better fetal outcome in all the three cases, in which ECT
was used close to full‑term. Many anesthetic agents such
as thiopentone, propofol, and methohexitone have been
used for induction during the ECT procedure. Among these
agents, methohexitone is not available in India, and use of
propofol during pregnancy is not approved. Accordingly,
thiopentone was safely used in the present case series. In
most of the earlier reports too, thiopentone was the most
commonly used anesthetic agent. In all the patients, ECT
was administered by placing the patients in the left lateral
position to avoid compression of abdominal aorta and
venacava. All patients were intubated after the procedure
to reduce the chances of aspiration. These precautions
were followed as per the recommendations of the available
guidelines[8] and good maternal and fetal outcome in the
present case series could also be due to the same.
ECT‑induced seizures are known to cause rise in oxytocin
levels, which increases the uterine contractions and induce
preterm labor.[6] In the current series, such eventuality was
possibly seen only in one patient (case – 2), who ultimately
required cesarean section due to nonprogression of labor.
Hence, it is important to monitor all the patients for uterine
contractions before, during and after ECT.
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Grover, et al.: ECT during pregnancy
In the present case series, all the patients received 5–7 ECTs
during pregnancy, which is lower than the mean numbers of
9.4 ECTs reported in the literature; however, the number of
ECT treatment are within the reported range of 1–35 ECTs.[2,3]
As per the available literature, the age of the patients who
received ECT varied from 16.5 to 48 years with a mean age of
28.9 (SD – 6.2) years.[3] In the present case series, the age range of
the patients was from 28 to 42 years. In the available literature,
both unilateral and bilateral ECT has been used; however, in the
current series, all patients received bilateral ECT.
In the current series, the level of symptom reduction among
patients varied from 65% to 81.2%, with two patients achieving
clinical remission. The effectiveness of ECT in patients with
schizophrenia was 65%–70%. Available literature suggests
that ECT during pregnancy is effective in more than 80%
of patients with affective disorders and the effectiveness
in patients with psychosis is 61%–66.7%.[3] Findings of the
present case series support the effectiveness of ECT during
pregnancy and suggests that whenever there is a need for an
effective treatment for the management of acute symptoms,
ECT must be considered as a useful option.[2]
The present case series adds to the limited literature and
provides evidence for safe use of ECT during pregnancy.
492
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Goldstein HH, Weinberg J, Sankstone MI. Shock therapy in psychosis
complicating pregnancy: A case report. Am J Psychiatry 1941;98:201‑2.
2. Anderson EL, Reti IM. ECT in pregnancy: A review of the literature from
1941 to 2007. Psychosom Med 2009;71:235‑42.
3. Leiknes  KA, Cooke  MJ, Jarosch‑von Schweder  L, Harboe  I, Høie B.
Electroconvulsive therapy during pregnancy: A systematic review of case
studies. Arch Womens Ment Health 2015;18:1‑39.
4. Sinha P, Goyal P, Andrade C. A Meta‑review of the safety of
electroconvulsive therapy in pregnancy. J ECT 2017;33:81‑8.
5. Pompili M, Dominici G, Giordano G, Longo L, Serafini G, Lester D, et al.
Electroconvulsive treatment during pregnancy: A systematic review.
Expert Rev Neurother 2014;14:1377‑90.
6. Miller  LJ. Use of electroconvulsive therapy during pregnancy. Hosp
Community Psychiatry 1994;45:444‑50.
7. Malhotra  N, Vani, Malhotra  P, Bhardwaj  R. Modified electroconvulsive
therapy during pregnancy. J Anaesthesiol Clin Pharmacol
2008;24:351‑2.
8. American Psychiatric Association. The Practice of Electroconvulsive
Therapy: Recommendations for Treatment, Training, and Privileging
(A Task Force Report of the American Psychiatric Association).
2nd ed.  Washington, D.C.: American Psychiatric Association; 2001.
Indian Journal of Psychiatry Volume 59, Issue 4, October-December 2017
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REVIEW ARTICLE

Mood stabilizers in pregnancy and lactation

Sandeep Grover, Ajit Avasthi
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

ABSTRACT

Management of bipolar during pregnancy and postpartum is very challenging. The treating clinicians have to take
into account various factors like current mental state, longitudinal history of the patient, past history of relapse while
off medication, response to medication, time of pregnancy at which patient presents to the clinician, etc. The choice
of drug should depend on the balance between safety and efficacy profile. Whenever patient is on psychotropic
medication, close and intensive monitoring should be done. Among the various mood stabilizers, use of lithium
during the second and third trimester appears to be safe. Use of valproate during first trimester is associated with
major malformation and long‑term sequalae in the form of developmental delay, lower intelligence quotient,
and higher risk of development of autism spectrum disorder. Similarly use of carbamazepine in first trimester is
associated with higher risk of major congenital malformation and its use in first trimester is contraindicated. Data
for lamotrigine (LTG) appears to be more favorable than other antiepileptics. During lactation, use of valproate and
LTG is reported to be safe. Use of typical and/atypical antipsychotic is a good option during pregnancy in women
with bipolar disorder.

Key words: Antipsychotics, bipolar disorder, mood stabilizers, pregnancy

INTRODUCTION acute manic symptoms, acute depressive symptoms and can

Mood stabilizer is the term used for the agents which are
useful in the treatment of bipolar disorders. However, the
definition of this class of drugs is not yet settled. Some
researchers/clinicians restrict the use the term mood
stabilizer for agents, which have efficacy in reducing the
frequency or severity of various type of episodes in bipolar
disorder without worsening the frequency or severity of
other types of episodes.[1‑3] Accordingly, antidepressants,
which can induce manic switch and typical antipsychotics,
which are shown to worsen depressive symptoms would
not classify as mood stabilizers. On the other hand, some
authors defined mood stabilizers as agents that have efficacy
in treating both manic and depressive symptoms.[4] Bauer
and Mitchner[5] expanded this definition and defined mood
stabilizer as an agent, which has efficacy in treatment of
prevent development of manic and depressive symptoms.[5]
Although the definition is not settled, mood stabilizers
are commonly understood as agents that are useful for
treatment of acute episodes (manic or depressive) and
prevention of relapse or recurrence of symptoms, without
worsening of symptoms of either polarity. In recent times,
many drugs have been evaluated as mood stabilizers.
The term mood stabilizers is mostly used in relation to
lithium, anticonvulsants like valproate, carbamazepine,
oxcarbazepine, lamotrigine, topiramate, gabapentin etc.,
and atypical antipsychotic like olanzapine, risperidone,
quetiapine, ziprasidone, and aripiprazole. Some other
drugs like clonazepam, calcium channel blockers etc., have
also been evaluated as mood stabilizers. In this paper, the
authors would limit to use of lithium, anticonvulsants,

Access this article online

Address for correspondence: Dr. Sandeep Grover,
Department of Psychiatry, Postgraduate Institute of Medical Quick Response Code
Education and Research, Chandigarh ‑ 160 012, India. Website:
E‑mail: drsandeepg2002@yahoo.com www.indianjpsychiatry.org

DOI:
How to cite this article: Grover S, Avasthi A. Mood stabilizers
10.4103/0019-5545.161498
in pregnancy and lactation. Indian J Psychiatry 2015;57:308-23.

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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
atypical antipsychotic and benzodiazepines in subjects with
bipolar disorders.
BIPOLAR DISORDER: RISK OF RECURRENCE
DURING PREGNANCY AND POSTPARTUM
Bipolar disorder is considered a severe mental disorder
that usually starts in late teens and early twenties and is
characterized by episodes of mania, depression, hypomania
and mixed episodes. The disorder has equal prevalence
in both genders. Women are exposed to the risk of an
episode throughout their reproductive life because of its
age of onset,[6] The decision to stop drugs when women
with bipolar disorder become pregnant or plan to conceive
is difficult. The treating psychiatrists of such patients face
the challenge of having to minimize the risk to the fetus,
while at the same time, limiting the impact of maternal
morbidity. Patients and their clinicians also face the reality
that decisions either to use or not to use psychotropic
medications can be associated with complications. Hence,
concluding as to what constitutes a reasonable risk during
pregnancy requires shared responsibility, but the ultimate
decision rests with the informed patient.
Studies have shown that female patients with bipolar
disorder are at high risk of relapse of symptoms during
the pregnancy[7‑9] and early postpartum period.[10‑13] The
risk of relapse during pregnancy has been estimated to
be 50% or more,[7‑9] with recurrence risk reported to be
2.3 times higher after discontinuation of mood stabilizer.
In a prospective study, it was found that women who
discontinued the mood stabilizer spent about 40% of the
time of pregnancy in episodes compared to 8.8% of time
spent by those who continued mood stabilizer. It was also
evident that the recurrence risk was higher and earlier after
rapid discontinuation of mood stabilizer. The authors also
found that women, who had younger age of onset, longer
duration of illness, more number of previous episodes,
history of rapid cycling, suicide attempts, associated
comorbid disorders and antidepressant use, had higher
chance of recurrence during the pregnancy. Treatment
discontinuation and antidepressant use remained as
independent risk factors even after adjusting for other risk
factors.[9]
With regard to the postpartum risk, studies have shown
that 40–70% of untreated bipolar women may experience
postpartum episode.[14] It is also known that the risk of
postpartum relapse is high in those who discontinue
prophylactic treatment.[13]
POTENTIAL RISKS OF PHARMACOTHERAPY IN
PREGNANCY IN BIPOLAR DISORDERS
For obvious ethical reasons, it is not possible to conduct
randomized placebo controlled studies on medication safety
Indian J Psychiatry 57 (Supplement 2), July 2015
in pregnant and lactating women. Most of the information
about the reproductive safety of drugs is derived from
case reports, case series, and retrospective studies. Very
few studies involve prospective design. Hence, knowledge
regarding the risks of prenatal exposure to psychotropic
medications remains far from complete. It is evident that all
psychotropic medications diffuse across the placenta, which
exposes the fetus to some degree of risk.[15] In the past, the
effects of psychopharmacological therapies was exclusively
discussed in the context of their risk during the first
trimester when organ formation occurs, it is now recognized
that psychotropics are harmful even after organogenesis, as
intrauterine exposure during the second and third trimester
can lead to postnatal complications.[16] Accordingly, the
impact of psychotropic drugs on the fetus and new born
has been studied in the form of teratogenicity (risk of
congenital physical deformities over the base line rate of
2.0–2.5%), obstetrical complications (preterm delivery, low
birth weight, low Apgar scores necessitating intensive care),
perinatal syndrome (physical and behavioral symptoms
noticed shortly after birth) and long‑term behavioral
sequelae (neurobehavioral abnormalities in children),
including long‑term neurobehavioral abnormalities in
children who were exposed to psychotropics in utero.[15]
REPRODUCTIVE SAFETY OF MOOD STABILIZERS
No psychotropic drug has been approved by the US Food
and Drug Administration (FDA) for use during pregnancy.
FDA has established a classificatory system for medications
based on data derived from human and animal studies.[17,18]
According to the risk, medications are classified into 5 risk
categories (A, B, C, D, and X). Medications placed in category
“A” are considered safe for use during pregnancy, however,
no psychotropic medication is classified as belonging
to category “A.” Medications placed in category X are
contraindicated due to demonstrated fetal risks, which
outweigh benefit to the patient. Drugs in categories B to
D are considered to have intermediate risks, which are
greatest in category D. Most antipsychotics are classified
as category C agents for which adequate human studies are
lacking and fetal effects are seen in animal studies or those
in which the animal studies are also insufficient; making
it difficult to rule out the fetal risks. Mood stabilizers like
lithium, valproate and carbamazepine are classified as
category “D” drugs.[15,17,18] It is important to remember that
this classification is not adequate for making all decisions
and the psychiatrists have to rely on other sources of
information when recommending the use of psychotropic
medications during pregnancy.[19,20]
MOOD STABILIZERS AND LACTATION
Breast milk is considered as an ideal form of nutrition
and is known to confer many advantages to the new born
and the infant. In addition, breast feeding is also known
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
to confer health benefits to mother. As per the American
Academy of Pediatrics,[21] human milk is known to reduce
the incidence and/or severity of a wide range of infectious
diseases including bacterial meningitis, bacteremia,
diarrhea, necrotizing enterocolitis, otitis media, respiratory
tract infection, urinary tract infection, and late‑onset sepsis
in preterm infants. In addition, breast feeding is also
reported to be associated with reduced postneonatal infant
mortality rates, decreased rates of sudden infant death
syndrome in the 1st year of life, lower incidence of type 1
and type 2 diabetes mellitus, Hodgkin disease, lymphoma,
leukemia, overweight and obesity, hypercholesterolemia
and asthma in older children and adults. Further, it is
suggested that breastfeeding is associated with slightly
enhanced performance on tests of cognitive development.
Breast feeding is also very important for development of
emotional bond and attachment between the mother and
the infant.[22,23] It is also known that continuation of breast
feeding decreases postpartum bleeding and leads to more
rapid uterine involution, decreased menstrual blood loss,
increased child spacing by lactational amenorrhea, earlier
return to prepregnancy weight, decreased risk of breast and
ovarian cancer, and possibly decreased risk of hip fractures
and osteoporosis in the postmenopausal period.[24]
Hence, asking the women not to feed the baby can lead to an
ethical dilemma. The decision regarding continuing or not
continuing breast feeding while continuing mood stabilizers
is a difficult one. Ideally, a risk benefit analysis should be
carried out taking into consideration the physiological
and psychological benefits of breastfeeding; the potential
adverse effect of untreated maternal mental illness on the
infant and maternal child bonding; impact of psychotropic
medication on the cognitive and behavioral development
of the infant, and the consequences of untreated mental
illness on the mother.[24] If a decision is taken to allow
continuation of breast feeding, it is important for the
clinicians to have basic knowledge about the physiological
aspects of milk secretion and the physiological maturation
of the newborn child. The exposure of infant to various
medications is dependent on the rate of absorption into
maternal circulation, diffusion from maternal circulation to
breast milk, and absorption of the agent in the infant. The
concentration of medications in breast milk is influenced
by lactose, serum albumin, lysozyme and approximately
30 other enzymes, prolactin, and minerals like calcium
and phosphates. It is known that, compared with the fore
milk (the milk ejected during the first half of a feeding),
hind milk (the milk ejected during the second half of a
feeding) has higher lipid content; hence, the milk secreted
in the second half will have a higher concentration of lipid
soluble maternal psychotropic medications than the first
half.[25] In terms of physiological maturation of the neonate,
it is important to remember that the amount of neonatal
cytochrome P‑450 activity is about half that found in adults.
Ability to conjugate various compounds develops from
S310 Indian J Psychiatry 57 (Supplement 2), July 2015
minimal levels to almost adult levels within 2 weeks of birth
in most cases.[26] Further, compared to adults, kidneys of
newborn are functionally immature; hence the psychotropic
medications that are predominately eliminated through
kidney may accumulate. Compared with adults, the blood
brain barrier in newborn is also immature, hence the lipid
soluble agents can be more concentrated (10–30 times) in
the cerebrospinal fluid than in serum and may be higher
in infants for a given plasma concentration. In addition,
compared to older infants, neonate have relatively lower
fat storage sites, accordingly central nervous system (CNS)
concentrations of lipid soluble substances are greater in
newborns.[25]
EFFECTS OF PSYCHOTROPICS: PREGNANCY AND
LACTATION
Lithium
Use of lithium in pregnancy has been a cause of concern
since the beginning because of the risk for major
congenital anomalies with prenatal exposure to lithium,
especially cardiovascular malformations such as Ebstein’s
anomaly.[27-29] As per the initial estimations, the risk for
Ebstein’s anomaly in infants with first trimester lithium was
400 times more than the background baseline rates.[27-30]
Cohen et  al.[30] carried out a metaanalysis and calculated
the risk for Ebstein’s anomaly, with first trimester exposure
to lithium, to be between 1/1000 (0.1%) and 1/2000 (0.05%)
births.[30] This risk was 10–20 times higher than the risk of
Ebstein’s anomaly in the general population. It is important
to understand that the absolute risk is small (0.05–0.1%),
and lithium is considered to be the safest mood stabilizer
for use during pregnancy.[30] Some of the recent studies
suggest increased risk of miscarriage.[31] In addition, use of
lithium has been associated with congenital abnormalities
like large for gestational age infants,[32] anencephaly,[33]
oromandibular‑limb hypogenesis[34] and premature closure
of arterial duct.[35] Exposure to lithium during labor and
delivery is associated with the risk of “floppy baby”
syndrome, which is characterized by muscular hypotonia
with impaired breathing and cyanosis in new born.[36-38]
Apart from this, there are occasional reports of neonatal
hypothyroidism, nephrogenic diabetes insipidus, and
polyhydramnios.[15,38,39]
Some groups recommend discontinuation of lithium
several days or weeks prior to delivery to minimize the
risk of neonatal toxicity.[31,37,39,40] Newport et al.[41] evaluated
the distribution of lithium concentration in umbilical
cord blood to maternal blood and reported that lithium
concentration was uniform (umbilical cord blood: Maternal
blood ratio = 1.05; standard deviation = 0.13) across a wide
range of maternal lithium concentrations (0.2–2.6 mEq/L).
In the same study, higher lithium concentrations
(>0.64 mEq/L) at delivery were associated with significantly
lower Apgar scores, higher rates of CNS and neuromuscular
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
complications in infants and resultant longer duration of
hospital stay. In was observed that withholding lithium
therapy for 24–48 h before delivery resulted in reduction
in maternal lithium concentration by 0.28 mEq/L, which
the authors considered could lead to improvement in
obstetrical outcome. A few reports have described adverse
effects in the form of lethargy, hypothermia, hypotonia,
and T‑wave modifications on electrocardiogram (ECG)
in newborns of mothers who continued to take lithium
during the postpartum period.[32,42,43] In a recent study,
the maximum recommended dose of lithium in pregnant
women, based on a physiologically based pharmacokinetic
model, was estimated and reported as 400 mg thrice
daily.[44] Data are limited with regard to the behavioral
outcomes of children exposed to lithium in utero. Follow‑up
studies of children (for 3.5–5 years) exposed to lithium
during pregnancy have come up with lack of evidence
for significant behavioral problems.[41,45] However, these
studies have been limited by small sample size. One of the
recent studies evaluated 15 children, exposed to lithium
prenatally, at the age of 3–15 years of age and reported
lower scores on the performance intelligence quotient (IQ),
although overall intelligence was within normal limits.
However, no abnormality was observed in growth, behavior
and general development.[46]
Anticonvulsants
Compared to lithium, higher teratogenic risk has been
reported to be associated with anticonvulsants. The risk
for major birth defects in infants born to women receiving
anticonvulsants has been reported to be twice that seen in
general population.[47] Further it is seen that the increased
risk for teratogenesis is associated with high maternal
serum anticonvulsant levels and exposure to multiple
anticonvulsants at a time.[48,49]
Valproate
Valproate is now considered as a mood stabilizer. It is
effective in management of acute manic and depressive
episodes and is also useful in prevention of relapse of both
manic and depressive episodes. Valproic acid and its various
derivatives have been known to have an increased risk of
causing neural tube defects in the range of 1.0–5.0%, which
is about 2–10‑fold higher than the general population base
rates of about 0.5%.[50,51] These risks are of concern because
neural tube formation occurs within the 1st month of
gestation, a time period during which the pregnancy is not
even diagnosed. The neural tube defect with valproate more
often involves the lumbosacral rather than the anencephalic
region, suggesting the effect of valproate on the closure
of neural crest.[52] Prenatal exposure to valproate has been
associated cardiovascular malformations, intrauterine
growth retardation, genital anomalies, hydrocephalus,
limb defects (radial ray effects, fibrous aplasia of lower
limbs), and pulmonary atresia.[47‑55] In a prospective study,
Wyszynski et al.,[53] evaluated the rate of occurrence of major
Indian J Psychiatry 57 (Supplement 2), July 2015
malformations at birth in infants of mothers who had taken
valproate as monotherapy and had enrolled in the North
American Antiepileptic Drug (AED) Pregnancy Registry.
Of the 149 valproate monotherapy exposed pregnancies,
major malformations were seen in 16 cases. When these
data were compared with the major malformations with
other anticonvulsants, it was concluded that valproate was
associated with more frequent adverse effects. Another
recent case–control study, which was based on European
Surveillance of Congenital Anomalies antiepileptic‑study
database, evaluated the outcome of exposure to valproic acid
monotherapy in 180 registrations. Compared to no use of
antiepileptic medications, use of valproic acid during the first
trimester was associated with increased risk of spina bifida,
atrial septal defect, cleft palate, hypospadias, polydactyl and
craniosynostosis.[56] Emerging data also suggest that the risk of
malformations with valproate is dose related[57,58] with higher
risk associated with use of valproate in excess of 1000 mg/
day.[57] Data based on the review of United Kingdom (UK)
and Ireland Epilepsy and Pregnancy Registers have estimated
the risk of major congenital malformations with valproate
monotherapy to be 6.7%, which is higher than that reported
for carbamazepine (2.6%) and lamotrigine (2.3%).[59]
Use of valproate close to delivery is associated with withdrawal
symptoms of abnormal tone, feeding difficulties, irritability
and jitteriness.[54] In addition, neonatal complications like
heart rate decelerations,[60] liver toxicity,[61] hypoglycemia,[62]
and reductions in neonatal fibrinogen levels[63] have
also been reported. Long‑term behavioral and cognitive
outcome with exposure to valproate in pregnancy has
been evaluated. Meador et al.[64] evaluated the IQ scores at
the age of 3 years of 258 children who were exposed to
anticonvulsants during pregnancy. IQs were lower for those
exposed to valproate compared to carbamazepine, LTG,
and phenytoin, after controlling for maternal IQs and blood
levels of anticonvulsant medications. It was further found
that maternal valproate blood level had significant inverse
correlation with cognitive functioning. A follow‑up of the
children at 4.5 years showed the persistence of lower IQ,
which was negatively associated with dose of valproate[65]
Subsequently, a large scale study evaluated IQ of children at
the age of 6 years and provided credence to this finding.[66]
A study also suggested that compared to the children
exposed to carbamazepine and lamotrigine, children
exposed to valproate prenatally have lower cognitive
fluency and originality.[67] Recent studies have also reported
neurodevelopmental delay in children exposed to valproate
prenatally.[68‑70] Another cause of concern is high rate of
autism spectrum disorder among the infants prenatally
exposed to valproate monotherapy with absolute risk of
4.42% for autism spectrum disorder and 2.5% for childhood
autism.[71,72] A recent review of data also suggests increase
in the risk of attention deficit hyperkinetic disorder with
antenatal exposure of valproate.[73]
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
With regard to secretion of valproate in breast milk, it has
been shown that valproate is minimally present in breast
milk. Piontek et  al.[74] evaluated the level of valproate in
6 breast‑fed mother‑infant pairs and reported that serum
valproate levels in the infants ranged from 0.9% to 2.3%
of the mother’s serum level. In another study of 2 infants
whose breastfeeding mothers were taking valproate,
Wisner and Perel[75] reported that valproate concentrations
in the infants were 1.5% and 6%, respectively. The American
Academy of Neurology and American Academy of Pediatrics
support breastfeeding if the mother is taking valproate.[76,77]
Carbamazepine
Use of carbamazepine during the first trimester of
pregnancy has been shown to be associated with the risk of
neural tube defects at a rate of about 0.5–1.0%.[78,79] Infants
exposed to carbamazepine prenatally are also at increased
risk for craniofacial abnormalities, fingernail hypoplasia,
developmental delay, growth retardation, microcephaly,
spina bifida, and cardiac abnormalities.[47,80] Recent data
suggest that the risk increases in a dose–dependent pattern
with higher risk with doses 400 mg/day.[81] Transient hepatic
toxicity (cholestatic hepatitis and direct hyperbilirubinemia)
in neonates exposed to carbamazepine during pregnancy
has also been noted.[80,82] In terms of behavioral and
cognitive outcome, studies have shown that carbamazepine
exposure during pregnancy and neonatal period does not
lead to significant cognitive dysfunction in childhood.[83,84]
The data on serum concentrations of carbamazepine among
breastfeeding infants are largely based on assessment of
newborns of mothers who were on carbamazepine during
the pregnancy. Evidence suggests that in general the
concentration of carbamazepine in breast milk is much
lower than the maternal serum levels, with concentrations in
infants ranging from 6% to 65% of maternal levels.[85] Studies
that have evaluated carbamazepine exposure in nursing
infants have reported occasional cases of transient hepatic
dysfunction.[80,82] Both American Academy of Neurology and
American Academy of Pediatrics support breastfeeding if
the mother is taking carbamazepine.[76,77]
Oxcarbazepine
Oxcarbazepine, a congener of carbamazepine has been used
for the treatment of bipolar disorders. In a review of data,
Eisenschenk[86] reported that, in the 248 patients identified in
the literature as receiving oxcarbazepine during pregnancy,
6 malformations were reported; indicating a malformation
risk of 2.4%, which is within the 2–4% malformation rate
seen in the general population. It is noteworthy that in 4,
out of the 6 pregnancies with congenital malformation,
the mothers were also receiving adjunctive antiepileptics.
The malformations reported include major cardiac
malformation (adjunctive therapy with phenobarbital),
ventricular septal defects (1 monotherapy and 1 adjunctive
therapy with lamotrigine), facial malformations (cleft soft
S312 Indian J Psychiatry 57 (Supplement 2), July 2015
palate, facial dysmorphism, terminal transverse defect,
disproportion of head and trunk, and extrophia vesicae) in
1 case, congenital hydronephrosis (adjunctive therapy with
vigabatrin), major urinary tract defect (1 case) and 1 case of
spina bifida cystica and clubfoot (adjunctive therapy with
valproate and clobazam).
Lamotrigine
In recent time use of lamotrigine in bipolar disorders has
increased. However, most of the data about its safety in
pregnancy is available from its use in pregnant females
with epilepsy. Newport et  al.[87] pooled the data from
the available studies and reported 2.6% risk (78/2974) of
major fetal anomalies following first trimester exposure
to lamotrigine, which is within the range of anomalies
among births reported in the general population. The
obstetrical outcome information is maintained by the
International lamotrigine Pregnancy Registry. Cunnington
et al.[88] reported that of the 414 first trimester exposures
to lamotrigine monotherapy, about 3% (12 offspring) had
major birth defects which are similar to that in general
population. However, no distinctive pattern of major birth
defects was apparent among the birth defects detected
following exposures to lamotrigine monotherapy. They
found a higher rate of major birth defects (12.5%) in 88 first
trimester exposures to combination of lamotrigine and
valproate. Recently, some data have emerged to suggest
that exposure to LTG is associated with increase in the
risk of oral clefts. Holmes et al.[89] presented the data from
North American AED Pregnancy Registry with regard to
lamotrigine. Of the 684 infants exposed to lamotrigine,
16 (2.3%) had major malformations. Five infants (7.3/1000)
had oral clefts (isolated cleft palate [3 cases], isolated cleft
lip [1 case], and cleft lip and palate [1 case]). The rate among
the lamotrigine‑exposed infants was 10.4‑fold higher in
comparison to unexposed infants (n = 206,224) surveyed
at birth at Brigham and Women’s Hospital in Boston.
However, another study based on data from UK Epilepsy and
Pregnancy Register, did not confirm this finding. The authors
reported data of 1229 pregnancies exposed to lamotrigine
as monotherapy, resulting in 1151 live births. Twenty‑eight
major congenital malformations were reported with no
specific pattern; of which only one male infant was born with
nonsyndromic cleft lip and palate.[90] Recent data suggest
that the risk increases in a dose dependent pattern with
higher risk with doses 300 mg/day.[81] Studies in women with
bipolar disorder treated with lamotrigine during pregnancy
suggest lower serum level to dose ratios during pregnancy
than during the postpartum period.[91] Studies also suggest
higher clearance level of lamotrigine during pregnancy
and suggest the need for dose adjustment.[92] In terms of
neurobehavioral effects a follow‑up study of 23 infants,
reported no neurobehavioral effects with lamotrigine at
12 months of age.[93] However, one recent report suggested
behavioral outcomes comparable to valproate. The children
had reduced nonverbal IQ scores, along with lower scores
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
on motor and sensory measures, lower scores on executive
functions, behavioral measures and attentional measures as
per the parent‑report.[94]
Few case reports and case series reported mean milk/plasma
ratios ranging from 0.40 to 0.61 for lamotrigine.[95‑99] One
recently published study involving 30 lactating mothers and
their infants reported a mean milk/plasma ratio of 41.3%
with a range of 5.7–147%. The authors also reported higher
lamotrigine concentrations in breast milk 4 h after maternal
dose, although this finding was not statistically significant.
Compared with maternal plasma concentrations, the
plasma concentrations in infants were 18.3%. Based on
these findings authors reported infant lamotrigine dose
to be 0.51 mg/kg/day, and compared to maternal dose and
the relative infant lamotrigine dose was 9.2%. Almost all
infants (7 out of 8) were found to have mild thrombocytosis
at the time of serum sampling. No other adverse events
were observed or reported in the breast‑fed infants.[100]
Topiramate
Animal studies have demonstrated craniofacial and
skeletal abnormalities.[101,102] Kwarta et  al.[103] reported 2
malformations (micrognathia, phimosis) in 29 pregnancies
exposed to topiramate monotherapy. Hunt et al.[104] reported
pregnancy outcome in patients receiving topiramate
based on UK Epilepsy and Pregnancy Register. In the 70
pregnancies exposed to topiramate monotherapy, 3 major
malformations were seen; 2 infants had cleft lip and cleft
palate and 1 had hypospadias. It was also seen that women
who gave birth to neonates with major malformation were
receiving relatively higher doses (mean ‑ 400 mg vs. 238 mg)
compared to women who gave birth to children without
malformation. It was also seen that out of 61 cases exposed
to monotherapy and for whom data was available, 6 infants
were born at 37 weeks of gestation or less. Further, of the
56 cases exposed to monotherapy and for whom full data
on gestational age and birth weight was available, 8 (14.3%)
were small for gestational age. However, in women receiving
topiramate as part of polypharmacy, 13 major malformations
were reported. It was observed that major malformation
rates were higher when topiramate was given along with
valproate than with other antiepileptics. A large sample
study based on the Global Medical Safety database, reported
pregnancy outcome of 589 cases. The most common
outcome was a live birth, noted in 75.55% of pregnancies.
However, this outcome varied based on the diagnosis for
which topiramate was used, with highest proportion of live
births seen in patients with epilepsy.[105] The risk of major
malformation with topiramate has been reported to be
4.2–9%.[105,106] Among the major malformations reported
cleft lip or palate anomalies, limb, hand, or other skeletal
anomalies and respiratory or cardiovascular anomalies were
more frequently documented.[105] Other reports also suggest
association of first trimester use of topiramate and oral cleft
lip/palate anomalies.[107] Other abnormalities related with
Indian J Psychiatry 57 (Supplement 2), July 2015
topiramate use include small for gestational age[108-110] and
microcephaly.[109]
Gabapentin
Animal studies have demonstrated delayed bone ossification,
hydronephrosis and increased rates of hydroureter.[101] No
information is available regarding its possible teratogenic
effects in humans. Ohman et al.[111] evaluated the outcome
of 6 pregnancies in women receiving gabapentin during
pregnancy and reported uneventful deliveries with birth
to healthy children in 5 out of the 6 pregnancies. In 1
pregnancy, there was a premature delivery at 33 weeks
of gestation. In terms of postdelivery complications, mild
hypotonia and cyanosis was seen in 1 infant, which started
8 h after delivery. However, the infant was discharged from
hospital after 4 days in a completely normal state. One
recent study compared the pregnancy related outcome
of 223 gabapentin exposed pregnancies with unexposed
pregnancies and reported higher rate of preterm birth and
low birth weight with gabapentin. Further those neonates
who were exposed to gabapentin near the delivery more
frequently required neonatal intensive care treatment. Two
neonates exposed to gabapentin were also reported to have
suffered from poor neonatal adaptation.[112]
With regard to transplacental transfer of gabapentin Ohman
et al.[111] reported accumulation of gabapentin with umbilical
cord/maternal plasma concentration ratios ranging from
1.3 to 2.1 (mean ‑ 1.7). However, the gabapentin plasma
concentrations declined with an estimated half‑life of
14 h in the newborns. Studies which have estimated the
concentration of gabapentin in milk suggest that mean
milk/maternal plasma concentration ratio is 1.0 (range,
0.7–1.3) from 2 weeks to 3 months. Accordingly, the
infant dose is estimated to be 0.2–1.3 mg/kg/day, which is
about 1.3–3.8% of the dose received by the mother. When
the plasma concentrations in the breast‑fed infants were
estimated, it was reported that the concentration in the infant
was about 12% of the mother’s plasma levels. However, this
concentration was not associated with any adverse effects.
Atypical antipsychotics
Atypical antipsychotics are quite frequently evaluated
for the treatment of various phases of mood disorders.
However, there is relatively little data available with regard
to the safety of these agents in pregnancy and lactation.
In this section, the data with regard to use of atypical
antipsychotics in pregnancy and lactation is reviewed,
irrespective of the disorder in which these were evaluated.
Olanzapine
Animal studies done in rodents did not reveal any
evidence of teratogenicity with olanzapine despite the
use of doses higher than those used clinically. There are
few studies which have evaluated the use of olanzapine
during pregnancy. Goldstein et  al.[113] reported outcomes
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
of 37 olanzapine‑exposed pregnancies ascertained
prospectively. Of the 37 pregnancies, 14 were terminated by
therapeutic abortions with no abnormalities reported in the
fetus. In the rest of the pregnancies (n = 23), normal birth
without complications occurred in 16 cases; spontaneous
abortion occurred in 3; stillbirth in 1; prematurity in 1;
postmaturity in 2 cases, with one of new born developing
perinatal complications in the form of meconium aspiration
after cesarean section; and no major malformation in
any case. The rates of complications were less than or
comparable to the range of base rates for general population.
Additionally, the authors also reported 11 retrospectively
identified cases, in which major malformations in the form
of dysplastic kidney (1 case) and Down syndrome (1 case)
was found. There were 2 spontaneous abortions and 1
fetal death. Perinatal complications were noted in 3 cases
and postperinatal complications in 2 cases. Overall, out of
11 cases, no complications were observed in only 1 case.
In a review, Gentile[114] reviewed the data of 248 reported
cases on olanzapine maintained by the manufacturer (Eli
Lilly) up to December 2006. Among these, spontaneous
abortion was reported in 24 cases and perinatal
complications in 49 cases. Various malformations which
had been recorded include renal malformation (n = 5),
additional thumb digit (n = 2) and one case each of bilateral
talipes, spontaneous abortion of severe deformed fetus,
pretragus fibrochondroma, clubfoot, anencephaly, absent
heart, cleft palate, ventricular septum defect, albino infant,
esophageal atresia, myelomeningocele plus hydrocephalus,
and absent fingers. However, it was also noted that some
of the cases in which malformations were found had also
received other concomitant medications. Further, the
authors pointed out that the manufacturer concluded that
the prevalence of adverse pregnancy outcome did not differ
from that found in the general population. In a recent
review of data maintained by Eli Lilly, outcome of data of
610 pregnancies exposed to olanzapine was presented. The
authors reported normal birth in two‑third (65.7%) of cases,
premature birth in 9.8%, spontaneous abortion in 9.3% and
congenital anomalies in 4.4% of pregnancies and perinatal
complications were seen in 8% of pregnancies.[115]
Levinson et al.[116] found 8 live births with no malformations,
1 spontaneous abortion, and one stillbirth. In a study which
evaluated the outcome of 79 olanzapine exposed pregnancies,
major malformations in the form of craniosynostosis and
ureteral reflux (n = 1), hand/finger reduction (n = 1),
ventricular septum defect and upper alimentary tract
malformation (n = 1) were observed.[117] In another
study involving 60 pregnancies exposed to olanzapine,
1 case of major malformation (midline defects, cleft lip,
encephalocele, and aqueductal stenosis) was reported.[118]
Various other case reports and case series have also
reported birth of healthy infants without complications
despite prenatal exposure to olanzapine.[119‑132] A few case
S314 Indian J Psychiatry 57 (Supplement 2), July 2015
reports have reported defects in the form of atrioventricular
canal defect and unilateral clubfoot,[133] hip dysplasia,[134]
meningocele and ankyloblepharon[135] and microcephaly
and anophthalmos.[136] In some of these studies, case
series and case reports development or worsening of
gestational diabetes mellitus was also noted.[125‑127] Perinatal
syndrome reported with use of olanzapine in pregnancy
includes preterm delivery, low birth weight, hypotonia,
neonatal respiratory complications, neonatal cardiovascular
complications,[129] Erb’s palsy, jaundice[128] and high birth
weight/large for gestational age.[128,129] With respect to the
postnatal long‑term effects, Gati et  al.[137] did not find any
postnatal behavioral sequelae in children up to the age of
6–10 years.
Few studies have evaluated the excretion of olanzapine in
breast milk. The relative dose in infant has been reported
to be in the range of 0.66–1.19%.[138,139] Data from about
40 cases are available with respect to olanzapine use
during breast feeding. Goldstein et al.[140] reported 26 cases
in which breast feeding was continued for 1–8 months.
Four infants developed adverse reactions in the form of
jaundice and sedation (1 case), shaking, poor sucking and
lethargy (1 case), protruding tongue (1 case) and diaper rash,
diarrhea, and sleep disorder (1 case). Kirchheiner et  al.[120]
reported temporary motor delay in a case whose mother
took olanzapine 10 mg/day during the lactation. However,
other case reports and case series have not reported
any untoward effects on the infant with continuation of
olanzapine in the dose range of 2.5–20 mg/day during
breast feeding.[128,138,141,142] In the recently published study,
data were available for 102 newborns/infants exposed to
olanzapine through breast milk. Adverse outcome in the
neonate or infant were reported in 15.6%, with commonly
reported adverse events in the form of sedation (3.9%),
irritability (2%), tremors (2%) and insomnia in 2% of neonates/
infants.[115] Studies that have followed up children exposed
to olanzapine through breast milk at 1–2 years of age,
report no increase in adverse outcomes when compared to
control group.[143]
Risperidone
Animal studies in rats have shown increased incidence of
pup deaths and stillbirth with use of risperidone during
pregnancy.[101] Rosengarten and Quartermain[144] reported
impaired learning and disrupted short‑term retention in
adulthood with use of risperidone in dam during pregnancy.
In their study of 49 risperidone exposed pregnancies in
humans McKenna et  al.[118] did not report a single case of
major malformations. Similarly, many studies have reported
no major malformations with use of risperidone.[145‑150]
However, there are a few case reports of agenesis of corpus
callosum,[101] and spontaneous abortions.[116] Reis and
Källén[117] reported 1 case of major malformation (anal atresia
along with pulmonary malformation) in 51 risperidone
exposed pregnancies. The postmarketing surveillance data of
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
713 pregnancies (prospective data for 516 and retrospective
data for 197 pregnancies) exposed to risperidone was
reported. Majority of the adverse pregnancy and fetal/
neonatal outcomes were reported for pregnancies for which
retrospective data was available. Among the prospectively
reported, out of the 68 pregnancies with known outcome,
organ malformations were observed in 3.8% and spontaneous
abortions occurred in 16.9% pregnancies. When compared to
the general population, the rates were comparable.[151] Of the
retrospectively reported outcome major organ malformations
were reported in 12 pregnancies. Major malformations
reported included cleft lip/palate (n = 2), and one case each
of esophageal atresia along with ear pinna hypoplasia and
slight facial dysmorphia, Ivemark syndrome, Moyamoya
disease, ventricular cyst in the brain, patent foramen ovale,
hypoplastic left heart, dilated cardiomyopathy, right auricular
achondroplasia, mild talipes equinovarus, gastroschisis,
and Pierre‑Robin syndrome. However, it is important to
remember that in some cases in which major malformations
were seen, the mothers also received other concomitant
medications.[151] In terms of neonatal outcome, McKenna et al.
[118]
concluded that there was no difference in the prevalence
rate of poor pregnancy outcome and perinatal complications
between the risperidone exposed group and a control group
exposed to nonteratogens. In the postmarketing surveillance
study,[151] perinatal syndrome (in the form of tremor,
jitteriness, irritability, feeding problems) was reported in 37
pregnancies, of which 21 cases involved behavioral or motor
disorders. Other adverse pregnancy outcomes reported with
use of risperidone include oligohydraminos,[150] small for
date,[152] and gestational diabetes mellitus.[117] A case report
of neuroleptic malignant syndrome in a pregnant women
receiving risperidone has also been documented.[153]
With regard to use of risperidone during lactation, studies
suggest that relatively low infant dose (0.84–4.7%) of the
weight adjusted maternal dose[154,155] and an additional
3.46% of its metabolite are transferred to infant.[155] The
data does not suggest any untoward neurodevelopmental
problems with risperidone.[150,155,156]
Quetiapine
Delay in skeletal ossifications, reduced fetal weight, and
increased fetal and pup deaths have been reported with
use of quetiapine in pregnancy in animal models.[101] In
human studies, quetiapine has been shown to have the least
placental passage (23.8%) compared to both first generation
antipsychotics (haloperidol) and other second generation
antipsychotics (risperidone and olanzapine). Most of the
human studies have not reported any major malformation or
neonatal problems with use of quetiapine in pregnancy.[157‑168]
McKenna et al.,[118] reported on the data maintained by the
manufacturer till March 2005. A total of 446 pregnancies
were exposed to quetiapine. In terms of congenital
malformation, out of the 151 pregnancies for which outcome
was reported, 8 pregnancies had congenital malformations;
Indian J Psychiatry 57 (Supplement 2), July 2015
with no commonality between the malformations seen. It is
important to note that concurrent medications were used in 7
of the 8 cases with congenital anomalies. In a postmarketing
surveillance study, out of the 6 cases, spontaneous abortion
was reported in 2 cases.[157] McKenna et al.[118] also reported
the outcome of 36 pregnancies exposed to quetiapine.
Although the authors did not report any specific congenital
anomalies associated with quetiapine, they concluded
that compared to a control group of women exposed to
nonteratogenic agents, quetiapine was not associated with
an increase of teratogenic risk.
With regard to excretion of quetiapine in breast milk,
studies suggest relatively low dose (0.09–0.43%) of the
weight adjusted maternal dose in infant[161,169] and the
quetiapine concentration in infant’s plasma is estimated to
be about 6% of the maternal drug concentration.[169]
Amisulpiride
Data from animal studies on mice and rabbits show lack of
teratogenic effect of amisulpride with doses up to 4 times
the maximum recommended human dose.[114] However,
data on the effect of amisulpride on human pregnancies are
lacking.
Ziprasidone
Use of ziprasidone in animals suggests its association with
developmental delays, possible teratogenic effects (cardiac,
renal, and skeletal), and increased still births.[101] One case
report presented the association of ziprasidone with cleft
palate,[170] whereas another case report reported on adverse
outcome of use of ziprasidone along with citalopram during
pregnancy and lactation.[171]
Aripiprazole
In animal studies aripiprazole has shown developmental
toxicity, including possible teratogenic effects in rats and
rabbits. The main effects were delayed skeletal ossification
and decreased fetal weight with 3–10 times the maximum
recommended human dose.[172] Only 13 case reports and
1 small case series (3 cases) have discussed the outcome of
aripiprazole exposed human pregnancies.[173‑184] In all cases
except one, no teratogenic effects were reported. However
it is important to note that in 9 out of the 16 pregnancies
aripiprazole was started after first trimester of gestation.
In one case minimal hip dysplasia was documented.[184] In
terms of neonatal and obstetrical outcome, 1 case required
caesarean section due to development of unexplained fetal
tachycardia.[174]
Sparse data are available with regard to use of aripiprazole
during lactation. Animal studies suggest that aripiprazole is
excreted in milk. One case report suggests failure of lactation
in women treated with aripiprazole in pregnancy.[173]
Another case report suggested lack of aripiprazole secretion
in breast milk.[178]
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
Clozapine
Clozapine is the only antipsychotic which belongs
to category B of FDA classification. Animal studies in
rats and rabbits reveal no harm to the fetus with doses
of approximately 2–4 times higher than the human
dose (clozapine prescribing information).[114] Data with
regard to use of clozapine in human pregnancy is available
only in the form of case reports/series and occasional
review. Waldman and Safferman[185] reported at least 15
normal births following maternal exposure to clozapine
in pregnancy. Many others also suggest no definitive
association between maternal exposure and congenital
anomalies in humans.[186‑192] A study which reported
outcome of 61 pregnancies exposed to clozapine revealed
5 congenital malformations and 5 perinatal syndromes.
[193]
Various other associations reported with maternal
exposure are decreased variability of fetal heart rate,[194,195]
delayed peristalsis,[196] delayed speech acquisition,[197] floppy
infant syndrome,[188] gastroesopahgeal reflux disease,[198]
intrauterine growth retardation with oligohydramnios
and intrauterine death,[199] neonatal seizures[189] and new
onset or worsening of gestational diabetes mellitus with
shoulder dystocia.[185,187] However, many of these findings
have been complicated by the concomitant use of other
drugs, malnutrition or family history of diabetes mellitus.
Clozapine overdose during pregnancy has also been
shown to lead to fatal poisoning in the newborn[200] and to
be associated with absent fetal heart rate variability and
delayed peristalsis in the newborn.[201]
As with other antipsychotics, data with regard to use of
clozapine during lactation is sparse. In one case series, 2 out
of the 4 infants breast‑fed by mothers receiving clozapine,
developed adverse events. In a case report, delayed speech
acquisition was reported in the new born whose mother
received clozapine during pregnancy and lactation.
Benzodiazepines and pregnancy
Benzodiazepines are used commonly in subjects
with bipolar disorders as adjunctive medications for
mood stabilization, agitation, and sleep problems. All
benzodiazepine compounds diffuse readily across the
placenta to the fetus and are secreted in breast milk. The
amount excreted depends on the oral bioavailability, plasma
protein binding, maternal blood concentrations, ionization,
molecular weight, half‑life, degree of lipophilicity and
pharmacokinetics of each benzodiazepine.[202] The use of
benzodiazepines in pregnancy has been reviewed in detail
by Iqbal et al.[202] The most important issues associated with
use of benzodiazepines in pregnancy shall be discussed here.
The risk of malformation is highest if the fetal exposure
occurs between 2 and 8 weeks of pregnancy. Further if
benzodiazepines are given at or near term, they may cause
fetal dependence and eventual withdrawal symptoms.[202]
S316 Indian J Psychiatry 57 (Supplement 2), July 2015
Diazepam
In a review of 599 oral clefts it was shown that use of
anxiolytics, mostly diazepam, during the first trimester
of pregnancy was associated with development of
oral clefts.[203] However, this has not been a consistent
finding in the later studies, with some reporting similar
association,[204‑206] while others not finding the same.[207‑210]
There are case reports of other malformations, however,
some of these have been inconclusive because of use of
other medications along with diazepam.[202] Use of high
doses of diazepam (usually more than 30–40 mg/day)
during labor has been associated with withdrawal symptoms
starting within a few days to 3 weeks and lasting up to
several months in neonates. The withdrawal symptoms are
characterized by hypertonia, hyperreflexia, restlessness,
irritability, abnormal sleep patterns, inconsolable crying,
tremors or jerking of the extremities, bradycardia,
cyanosis, suckling difficulties, apnea, risk of aspiration
of feeds, diarrhea and vomiting, and growth retardation.
Other reports suggest that use of high doses may also be
associated with “floppy infant syndrome” characterized by
withdrawal symptoms, hypothermia, lethargy, respiratory
problems, and feeding difficulties.[202] Use of diazepam
during late pregnancy and labor has also been associated
with development of prolonged hyperbilirubinemia of the
newborn and potentially to kernicterus. This has been linked
to the preservative (sodium benzoate) in the diazepam
formulation, which competes with diazepam for plasma
protein binding.[202]
Although occasional reports have associated the therapeutic
use of diazepam with congenital malformation, the bulk
of the evidence indicates that the use of diazepam during
gestation has no adverse effects on the child’s development
if used in low doses.[202] However, it is to be remembered
that when it is used near term, the dosage should be
tapered off over weeks to avoid development of neonatal
withdrawal and floppy infant syndrome.
Low dose use of diazepam either just before the delivery or
during postpartum by the mother is associated with sedation
in the new born. In general, low concentration of diazepam
has been found in breast milk; however, the concentration
varies with maternal dose. Use of higher doses of diazepam
during breast feeding is associated with lethargy and weight
loss in the neonate, which improves after stopping breast
feeding. Hence, while using diazepam during pregnancy
or labor the treating doctors should be aware of the side
effects and must take appropriate measures.[202]
Clonazepam
Use of clonazepam in pregnancy has been shown to be
associated with apnea, bilateral inguinal hernia, congenital
heart disease, cyanosis, hip dislocation, hypotonia lethargy,
paralytic ileus of the small bowel, undescended testicle,
uteropelvic junction obstruction, and ventral septal
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
defect.[202] However, it is important to note that in most
cases clonazepam was used along with other antiepileptics
like phenytoin and barbiturates.
Use of clonazepam during lactation has also shown to be
associated with apnea, CNS depression, cyanosis, excessive
periodic breathing and hypotonia. Hence, clonazepam
should be used during pregnancy and lactation only when
the clinical benefit to the mother justifies the risks to the
fetus and newborn. If used, the fetus and the newborn
should be closely monitored.[202]
Lorazepam
Use of lorazepam during pregnancy has been associated with
anal atresia and neonatal withdrawal symptoms. The latter
can be severe, because of the short half‑life of lorazepam,
and are characterized by low Apgar scores, depressed
respiration, hypothermia, poor suckling and jaundice. Thus,
injectable lorazepam should be avoided during pregnancy
as far as possible.[202] Oral lorazepam should be used during
pregnancy only in life‑threatening situations or in cases of
severe disease for which other safer drugs cannot be used or
are ineffective.
In breast milk, lorazepam is secreted in low quantity and is
considered to be relatively safe.[202]
Alprazolam
Use of alprazolam in pregnancy has not been shown to
be associated with increased risk of major malformations.
However, it has been linked with malformations like ankle
inversion, cat’s eye with Pierre‑Robin syndrome, cleft
lip, congenital hip dislocation, cryptorchidism, Down’s
syndrome, fused lacrimal duct, hypospadias, inguinal
hernia, lipomeningocele, microcephaly, patent ductus
arteriosus, pyloric stenosis, strabismus, tracheoesophageal
fistula, umbilical hernia and neonatal withdrawal syndrome.
Thus, it should preferably not be used in first trimester and
during lactation.[202]
MANAGEMENT OF BIPOLAR DISORDERS IN
PREGNANCY AND LACTATION
Clinicians handling the bipolar disorders are usually faced
with the following situations:
• A patient of bipolar disorder on medications wanting to
conceive
• A patient of bipolar disorder already conceived (on/not
on medications), but the symptoms are under‑control
• A patient of bipolar disorder already conceived  (on/
not on medications), but the symptoms are present/
experiencing relpase
• First episode mania during the pregnancy
• First episode mania during the early postpartum period
• Continuation of medications during lactation.
Indian J Psychiatry 57 (Supplement 2), July 2015
There is no single answer to all the above situations. All
the decisions about continuation or initiation of treatment
during pregnancy in subjects with known bipolar disorders
must take into account: (i) The highly variable, but often
poorly quantified risks of fetal exposure to drugs (ii) the
substantial risks to the patient, fetus, and family from
untreated illness in the mother; and (iii) high risk of relapse
associated with discontinuation of maintenance treatment,
particularly if it is done abruptly. Each of these risks should
be discussed in detail with the patient and her spouse and
other close family members.
If a woman with bipolar disorder, who is on medication,
expresses her wish to conceive, the clinician should take
into consideration the illness history, acceptability and
estimated safety of specific clinical interventions, which
may be pharmacologic or nonpharmacologic. Specific
considerations include the frequency and severity of
previous episodes, past and current levels of functioning
or impairment, past and recent duration of clinical
stability with and without medication, the nature of
prodromal symptoms that indicate an impending relapse,
and average time to recovery following re‑introduction of
treatment. In the assessment process, it is also important
to assess the usefulness of previous medication trials
in terms of responses rate, adverse effects and effect of
discontinuation of treatment.[15] In addition to assessing
the illness and the effectiveness of current and past
treatments, clinicians should also take into consideration
other risk factors (e.g., poor nutrition, smoking, alcohol
use etc.), which can contribute to poor perinatal outcome.
Emphasis should also be on promotion of healthy behaviors
like adherence to a prenatal vitamin regimen and regular
prenatal checkups and healthy diet.[211]
If a woman with bipolar disorder plans to conceive, following
options can be considered: Discontinue the mood stabilizer
prior to conception, continue treatment until pregnancy is
verified or continue treatment throughout the pregnancy.
All these decisions would depend on the severity of illness
and past treatment response. Discontinuation of mood
stabilizer during the pregnancy phase may be considered
if there is past history of one or infrequent episodes with
long period of remission. If such an attempt is made it is
important to remember that the pharmacological agents
should be tapered off slowly and the women should be
closely monitored for conception and relapse of symptoms.
An alternative strategy is to continue treatment until
pregnancy is verified, and then gradually taper off the mood
stabilizer. Uteroplacental circulation is not established
until approximately 2 weeks postconception and the early
risk of fetal exposure is minimal. The advantages of this
strategy are that it minimizes fetal exposure to drugs
and extends the protective treatment up to the time of
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
conception.[15] However, it is important to remember
that this strategy may lead to relatively abrupt treatment
discontinuation, thereby placing the patient at increased
risk for relapse.[13,19,29]
In ideal situation, the patient should discuss about her
plan of pregnancy and this should be when the patient is
euthymic. Based on the patient’s history, decision should
be taken about continuation of medication during the
period before conception and during the first trimester. If
the patient is clinically stable an attempt to discontinue the
mood stabilizer prior to conception should be taken.
If there is recurrence of symptoms during the discontinuation
trial, then a difficult choice to continue taking medication
during pregnancy has to be made.[211]
If on the basis of history the illness is considered to be
severe (chances of relapse are high without medication),
then the psychiatrists should discuss with the patient and
the spouse about continuation of mood stabilizer during
the conception period also. In some cases, mood stabilizers
could be continued till the confirmation of conception
and then these could be withdrawn cautiously, but close
monitoring for relapse should be done.[211] For women with
severe forms of bipolar disorder, for example, multiple
severe episodes and especially with history of psychotic
symptoms and suicidal attempts, maintenance treatment
with a mood stabilizer before and during pregnancy may be
the safest option. In such a situation, lowest effective dose
of a medication must be used and medications which have
the least teratogenic potential should be selected. However,
in certain cases of refractory illness, in which the patient has
responded to a newer agent for which reproductive safety
data are not available or is sparse, the clinician should
consider to continue the same agent after explaining the
pros and cons of continuing the same medication to the
patient and family.[15]
If the patient is on lithium, valproate or carbamazepine
before conception, the risk should be discussed with
patient and spouse and wherever possible these should be
stopped during the first trimester or be replaced by other
safer options like a typical antipsychotic. It is important
to remember that typical antipsychotics increase prolactin
levels and thereby disrupt the menstrual cyclicity and hence
adversely affect fertility;[211] so whenever possible, an agent
with less effect on prolactin and better teratogenicity safety
profile should be preferred.
For women who tolerate discontinuation of maintenance
treatment, the decision when to restart the treatment
depends on the clinician and the patient. Some patients
and clinicians may prefer to wait for the initial signs and
symptoms to appear before restarting medication, while
others may prefer to limit risk of a major recurrence by
S318 Indian J Psychiatry 57 (Supplement 2), July 2015
restarting treatment after the first trimester of pregnancy.
If the treatment has to be restarted, the decision about
the mood stabilizer should take into consideration the
past history of response and the risk associated with a
particular agent during the second and third trimester.
It is generally considered that if a woman has done well
on a particular mood stabilizer then changing the mood
stabilizer for avoiding potential risk to offspring may risk
the woman stability and may not be a right decision. Hence,
continuation of the same mood stabilizer with informed
consent of the patient and spouse should be preferred.
If the recurrence of symptoms during pregnancy is in the
form of mild to moderate depression, psychotherapeutic
interventions may be tried before considering the mood
stabilizer depending on the patient’s motivation for such
therapy and past response. However, if the depression is
severe, antidepressants (a selective serotonin reuptake
inhibitor [but not paroxetine]) or electroconvulsive therapy
can be considered.[15]
Unplanned pregnancy
Unfortunately, about 50% of pregnancies in women with
bipolar disorders are unplanned. In many instances,
pregnancy is detected during or after the highest risk
period for some agents has passed. Discontinuation of the
medication after the risk period has passed may place the
woman at risk without conferring any appreciable benefit.
The variables which must be taken into account while
finalizing the treatment plan include the clinical stability
of the patient, duration of pregnancy, psychotropic agent
which the patient is taking and treatment preferences of
the patient.
If the patient has not completed the first trimester and
reports with confirmed pregnancy, the pros and cons
about the medication continuation and abrupt stoppage
of medication have to be discussed. If the patient is on
anticonvulsants, then a high dose of folic acid should be
prescribed for the woman. If it is not possible to stop the
medication then attempt should be made to reduce the
dose to minimum.
If the patient has completed the first trimester of pregnancy,
then the patient and the spouse should be explained about
the pros and cons of continuation of pregnancy, depending
on the agent, which the patient was taking. If the patient
had been on polypharmacy, then the additional risk should
be emphasized.
If the decision to continue the pregnancy is made, the
decision about the mood stabilizer should take past history
of response and the risk associated with a particular agent
during the second and third trimester. Continuation of the
same mood stabilizer with informed consent of the patient
and spouse should be preferred. However, some authors
suggest that if the woman is on valproate and if there is
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
no history of nonresponse to lithium, the switch to lithium
should be considered.[212]
Monitoring while continuation of mood stabilizers during
pregnancy
If mood stabilizers are continued during pregnancy,
prenatal screening for congenital malformation with a
high resolution ultrasound and fetal echocardiography is
recommended around 16–18 weeks of gestation to screen
for cardiac anomalies. The possibility of fetal neural tube
defects should be evaluated with maternal serum alpha
fetoprotein and ultrasonography. In addition, use of folic
acid is recommended prior to conception and during
the first trimester for women receiving anticonvulsants,
although it is unknown whether supplemental folic acid
can reduce the risk of neural tube defects in the setting
of anticonvulsant exposure.[49,213] For patients who are
continued on carbamazepine or oxcarbazepine, Vitamin K
supplementation (10 mg/day orally) during the last month
of pregnancy is recommended. The new born should also
receive 1 mg of Vitamin K intravenously or intramuscularly
on day 1 after delivery.[76]
Monitoring while continuation of mood stabilizers near
the term/labor
Some experts suggest that the dose of lithium should be
reduced at the onset of labor to avoid toxicity resulting
from the rapid reduction of vascular volume at delivery.[214]
Close monitoring of symptoms and serum lithium levels are
required to avoid relapse or toxicity during delivery and the
immediate postpartum period.[13,29]
Treatment during postpartum
Puerperium is the period of heightened risk of relapse
for subjects with bipolar disorders. Hence, restarting of
mood stabilizer during immediate postpartum should be
considered strongly in subjects with high risk of relapse, as
data show that use of lithium as a prophylactic agent in the
postpartum period reduces the rate of relapse from nearly
50% to <10%.[215,216]
First episode during pregnancy and puerperium
For women who develop first episode of mania during
pregnancy, the psychiatrist is called upon to decide about
which medication to start. In such a scenario, the decision
about the mood stabilizer is a tricky one and should take
into consideration the severity of symptoms, risk to the
mother and the fetus. If the patient has not completed first
trimester of pregnancy, typical high potency antipsychotic
or atypical antipsychotic like clozapine, olanzapine or
risperidone should be tried before considering lithium,
valproate or carbamazepine. If the women has completed
first trimester, then also antipsychotic should be
preferred over lithium (because of risk associated during
labor), valproate (long‑term cognitive side effects) and
carbamazepine. If one of these 3 agents has to be used
Indian J Psychiatry 57 (Supplement 2), July 2015
during the second or third trimester, lithium should be
preferred over carbamazepine and valproate. The patient
and the spouse should be explained about the risk with
such medications. If one has to use benzodiazepines, they
should be used for shortest possible duration in minimal
dose and should preferably be tapered off slowly with
monitoring of fetus.
Breast feeding with mood stabilizers
Whether to allow breast feeding while continuing mood
stabilizers is a difficult decision. Breast feeding is very
important for development of emotional bond and
attachment between the mother and the infant.[22,23] Further,
it confers many physical health benefits to the mother and
the newborn. Hence, risk benefit analysis should take into
consideration the physiological and psychological benefits
of breastfeeding, wishes of the mother, risk of infant
exposure to the medication, and the possibility that a
severely ill mother may forego treatment rather than give
up breastfeeding.[25]
While continuing breast feeding with mood stabilizers, the
infant should be clinically monitored to minimize the risk.
Before starting breast feeding, the infant should be evaluated
by a pediatrician for baseline behavior, sleep, feeding, and
alertness. Parents should be alerted to the side effect profile
of medications, and regular clinical monitoring should be
done by the pediatrician to ensure normal development.
It is to be remembered that metabolism and elimination
are more efficient in older infants, who generally sleep
for longer durations, permitting dosing of the mother just
after nursing and before the baby’s longest sleep interval.
A close liaison must be kept with the pediatrician who can
be educated about the potential side effects of medication
exposure and interactions with other medications typically
prescribed to infants (e.g., antibiotics, nonsteroidal
antiinflammatory agents, and acetaminophen).[25]
While using a mood stabilizer, the clinician should titrate the
dose to the minimum effective dose. However, in such an
attempt clinician should not end up in using ineffective dose
and exposing the neonate to the medication unnecessarily.
If any medication is used on as and when required basis
then short‑acting agents should be preferred. Further, it
is best to use medications in which the parent compound
does not metabolize into several generations of active
compounds.[25]
According to the American Academy of Pediatrics,
breastfeeding should be undertaken with caution by women
undergoing lithium treatment. The breast‑fed infant should
be monitored for serum lithium levels, electrocardiogram
and complete blood counts. With regard to valproate and
carbamazepine both American Academy of Neurology and
American Academy of Pediatrics support breastfeeding if the
mother is taking valproate,[76,77] but the liver function tests
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Grover and Avasthi: Mood stabilizers in pregnancy and lactation
and blood counts of the newborn need to be monitored.
With regard to lamotrigine, the emerging data suggest that
it may be relatively safe during breast feeding. It should
be used during lactation when other safer options are not
available. Data for other anticonvulsants is preliminary. Data
with regard to atypical antipsychotics are also preliminary
and inconclusive.
CONCLUSION
From the literature, it is evident that the safety of mood
stabilizers in pregnancy is still unresolved. The decision to
prescribe them during pregnancy should be taken in light of
severity of mental disease and drugs should be prescribed
only when the potential risk to the fetus from exposure to
medication is outweighed by the risk of untreated maternal
disorder. The choice of drug should depend on the balance
between safety and efficacy profile. Whenever patient is
on psychotropics, close and intensive monitoring should
be done. An algorithm of treatment options should take
into consideration the severity of illness and the individual
patient’s unique treatment needs.
REFERENCES
1. Sachs GS. Treatment‑resistant bipolar depression. Psychiatr Clin North
Am 1996;19:215‑36.
2. Bowden CL. New concepts in mood stabilization: Evidence for the
effectiveness of valproate and lamotrigine. Neuropsychopharmacology
1998;19:194‑9.
3. Ketter TA, Calabrese JR. Stabilization of mood from below versus above
baseline in bipolar disorder: A new nomenclature. J Clin Psychiatry
2002;63:146‑51.
4. Calabrese JR, Rapport DJ. Mood stabilizers and the evolution of
maintenance study designs in bipolar I disorder. J Clin Psychiatry
1999;60 Suppl 5:5‑13.
5. Bauer MS, Mitchner L. What is a “mood stabilizer”? An evidence‑based
response. Am J Psychiatry 2004;161:3‑18.
6. Yonkers KA, Wisner KL, Stowe Z, Leibenluft E, Cohen L, Miller L, et al.
Management of bipolar disorder during pregnancy the postpartum period.
Focus 2005;3:266‑79.
7. Freeman MP, Smith KW, Freeman SA, McElroy SL, Kmetz GE, Wright R,
et al. The impact of reproductive events on the course of bipolar disorder
in women. J Clin Psychiatry 2002;63:284‑7.
8. Jones I, Craddock N. Bipolar disorder and childbirth: The importance of
recognising risk. Br J Psychiatry 2005;186:453‑4.
9. Viguera  AC, Whitfield  T, Baldessarini  RJ, Newport  DJ, Stowe  Z,
Reminick A, et al. Risk of recurrence in women with bipolar disorder during
pregnancy: Prospective study of mood stabilizer discontinuation. Am J
Psychiatry 2007;164:1817‑24.
10. Pugh TF, Jerath BK, Schmidt WM, Reed RB. Rates of mental disease
related to childbearing. N Engl J Med 1963;268:1224‑8.
11. Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses.
Br J Psychiatry 1987;150:662‑73.
12. Terp IM, Mortensen PB. Post‑partum psychoses. Clinical diagnoses and
relative risk of admission after parturition. Br J Psychiatry 1998;172:521‑6.
13. Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini RJ.
Risk of recurrence of bipolar disorder in pregnant and nonpregnant
women after discontinuing lithium maintenance. Am J Psychiatry
2000;157:179‑84.
14. Jefferson JW, Greist J, Ackermann D. Lithium Encyclopaedia for Clinical
Practice. 2nd ed. Washington, DC: American Psychiatric Press; 1987.
p. 504‑25.
15. Viguera AC, Cohen LS, Baldessarini RJ, Nonacs R. Managing bipolar
disorder during pregnancy: Weighing the risks and benefits. Can J
Psychiatry 2002;47:426‑36.
16. Cordero JF, Oakley GP Jr. Drug exposure during pregnancy: Some
epidemiologic considerations. Clin Obstet Gynecol 1983;26:418‑28.
17. Food and Drug Administration. Labeling and prescription drug advertising:
S320 Indian J Psychiatry 57 (Supplement 2), July 2015
Content and format for labeling for human prescription drugs. Fed Regist
1979;44:37434‑67.
18. Key to FDA‑in‑use pregnancy ratings. In: Physicians’ Desk Reference.
49th ed. Montvale, NJ: Medical Economics Data Production Co.; 1995.
p. 2597.
19. Cohen LS, Rosenbaum JF. Psychotropic drug use during pregnancy:
Weighing the risks. J Clin Psychiatry 1998;59 Suppl 2:18‑28.
20. Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA,
et al. Update on new developments in the study of human teratogens.
Teratology 2002;65:153‑61.
21. American academy of paediatrics-section on breastfeeding. Breastfeeding
and the use of human milk. Pediatrics. 2012;129:e827-41.
22. Newton N, Newton M. Psychologic aspects of lactation. N Engl J Med
1967;277:1179‑88.
23. Britton JR, Britton HL, Gronwaldt V. Breastfeeding, sensitivity, and
attachment. Pediatrics 2006;118:e1436‑43.
24. Gartner LM, Morton J, Lawrence RA, Naylor AJ, O’Hare D,
Schanler RJ, et al. Breastfeeding and the use of human milk. Pediatrics
2005;115:496‑506.
25. Burt VK, Suri R, Altshuler L, Stowe Z, Hendrick VC, Muntean E. The
use of psychotropic medications during breast‑feeding. Am J Psychiatry
2001;158:1001‑9.
26. Beath SV. Hepatic function and physiology in the newborn. Semin
Neonatol 2003;8:337‑46.
27. Nora JJ, Nora AH, Toews WH. Letter: Lithium, Ebstein’s anomaly, and
other congenital heart defects. Lancet 1974;2:594‑5.
28. Schou M. Lithium treatment during pregnancy, delivery, and lactation: An
update. J Clin Psychiatry 1990;51:410‑3.
29. Weinstein MR. The international register of lithium babies. Drug Inf J
1976;10:94‑100.
30. Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML.
A reevaluation of risk of in utero exposure to lithium. JAMA 1994;271:146‑50.
31. Diav‑Citrin O, Shechtman S, Tahover E, Finkel‑Pekarsky V, Arnon J,
Kennedy D, et al. Pregnancy outcome following in utero exposure to
lithium: A prospective, comparative, observational study. Am J Psychiatry
2014;171:785‑94.
32. Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, et al.
Prospective multicentre study of pregnancy outcome after lithium
exposure during first trimester. Lancet 1992;339:530‑3.
33. Grover S, Gupta N. Lithium‑associated anencephaly. Can J Psychiatry
2005;50:185‑6.
34. Tekin M, Ellison J. Oromandibular‑limb hypogenesis spectrum and
maternal lithium use. Clin Dysmorphol 2000;9:139‑41.
35. Ellis DL, Guerra V, Pridjian G, Recto MR. Possible association between
maternal lithium therapy and premature closure of the arterial duct. A case
report. J Reprod Med 2013;58:181‑4.
36. Schou  M, Goldfield  MD, Weinstein  MR, Villeneuve  A. Lithium and
pregnancy. I. Report from the Register of Lithium Babies. Br Med J
1973;2:135‑6.
37. Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and management
of women with bipolar disorder during pregnancy and lactation. J Clin
Psychiatry 1998;59 Suppl 6:57‑64.
38. Yonkers KA, Little BB, March D. Lithium during pregnancy: Drug effects
and therapeutic implications. CNS Drugs 1998;4:261‑9.
39. Ananth J. Side effects on fetus and infant of psychotropic drug use during
pregnancy. Int Pharmacopsychiatry 1976;11:246‑60.
40. Schou M. What happened later to the lithium babies? A follow‑up study of
children born without malformations. Acta Psychiatr Scand 1976;54:193‑7.
41. Newport DJ, Viguera AC, Beach AJ, Ritchie JC, Cohen LS, Stowe ZN.
Lithium placental passage and obstetrical outcome: Implications for clinical
management during late pregnancy. Am J Psychiatry 2005;162:2162‑70.
42. Woody JN, London WL, Wilbanks GD Jr. Lithium toxicity in a newborn.
Pediatrics 1971;47:94‑6.
43. Tunnessen WW Jr, Hertz CG. Toxic effects of lithium in newborn infants:
A commentary. J Pediatr 1972;81:804‑7.
44. Horton S, Tuerk A, Cook D, Cook J, Dhurjati P. Maximum recommended
dosage of lithium for pregnant women based on a PBPK model for lithium
absorption. Adv Bioinformatics 2012;2012:352729.
45. Skausig OB, Schou M. Breast feeding during lithium therapy. Ugeskr
Laeger 1977;139:400‑1.
46. van der Lugt NM, van de Maat JS, van Kamp IL, Knoppert‑van der
Klein EA, Hovens JG, Walther FJ. Fetal, neonatal and developmental
outcomes of lithium‑exposed pregnancies. Early Hum Dev 2012;88:375‑8.
47. Yerby MS. Problems and management of the pregnant woman with
epilepsy. Epilepsia 1987;28 Suppl 3:S29‑36.
48. Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S,
Hayes AM, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med
2001;344:1132‑8.
49. Lindhout D, Omtzigt JG. Teratogenic effects of antiepileptic drugs:
Implications for the management of epilepsy in women of childbearing
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Grover and Avasthi: Mood stabilizers in pregnancy and lactation
age. Epilepsia 1994;35 Suppl 4:S19‑28.
50. Robert E, Guibaud P. Maternal valproic acid and congenital neural tube
defects. Lancet 1982;2:937.
51. Omtzigt JG, Los FJ, Grobbee DE, Pijpers L, Jahoda MG, Brandenburg H,
et al. The risk of spina bifida aperta after first‑trimester exposure to
valproate in a prenatal cohort. Neurology 1992;42:119‑25.
52. Kennedy D, Koren G. Valproic acid use in psychiatry: Issues in treating
women of reproductive age. J Psychiatry Neurosci 1998;23:223‑8.
53. Wyszynski DF, Nambisan M, Surve T, Alsdorf RM, Smith CR, Holmes LB,
et al. Increased rate of major malformations in offspring exposed to
valproate during pregnancy. Neurology 2005;64:961‑5.
54. Koch S, Lösche G, Jager‑Romän E, Jakob S, Rating D, Deichl A, et al.
Major and minor birth malformations and antiepileptic drugs. Neurology
1992;42 4 Suppl 5:83‑8.
55. Cole RL, Van Ross ER, Clayton‑Smith J. Fibular aplasia in a child exposed
to sodium valproate in pregnancy. Clin Dysmorphol 2009;18:37‑9.
56. Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, et al. Valproic
acid monotherapy in pregnancy and major congenital malformations.
N Engl J Med 2010;362:2185‑93.
57. Mawhinney E, Campbell J, Craig J, Russell A, Smithson W, Parsons L,
et al. Valproate and the risk for congenital malformations: Is formulation
and dosage regime important? Seizure 2012;21:215‑8.
58. Vajda FJ, O’Brien TJ, Graham JE, Lander CM, Eadie MJ. Dose
dependence of fetal malformations associated with valproate. Neurology
2013;81:999‑1003.
59. Campbell E, Kennedy F, Russell A, Smithson WH, Parsons L, Morrison PJ,
et al. Malformation risks of antiepileptic drug monotherapies in pregnancy:
Updated results from the UK and Ireland Epilepsy and Pregnancy
Registers. J Neurol Neurosurg Psychiatry 2014;85:1029‑34.
60. Jäger‑Roman E, Deichl A, Jakob S, Hartmann AM, Koch S, Rating D, et al.
Fetal growth, major malformations, and minor anomalies in infants born to
women receiving valproic acid. J Pediatr 1986;108:997‑1004.
61. Felding I, Rane A. Congenital liver damage after treatment of mother with
valproic acid and phenytoin? Acta Paediatr Scand 1984;73:565‑8.
62. Thisted E, Ebbesen F. Malformations, withdrawal manifestations, and
hypoglycaemia after exposure to valproate in utero. Arch Dis Child
1993;69:288‑91.
63. Majer RV, Green PJ. Neonatal afibrinogenaemia due to sodium valproate.
Lancet 1987;2:740‑1.
64. Meador KJ, Baker GA, Browning N, Clayton‑Smith J, Combs‑Cantrell DT,
Cohen M, et al. Cognitive function at 3 years of age after fetal exposure to
antiepileptic drugs. N Engl J Med 2009;360:1597‑605.
65. Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL,
Clayton‑Smith J, et al. Effects of fetal antiepileptic drug exposure:
Outcomes at age 4.5 years. Neurology 2012;78:1207‑14.
66. Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL,
Clayton‑Smith J, et al. Fetal antiepileptic drug exposure and cognitive
outcomes at age 6 years (NEAD study): A prospective observational study.
Lancet Neurol 2013;12:244‑52.
67. McVearry KM, Gaillard WD, VanMeter J, Meador KJ. A prospective
study of cognitive fluency and originality in children exposed in utero to
carbamazepine, lamotrigine, or valproate monotherapy. Epilepsy Behav
2009;16:609‑16.
68. Cummings C, Stewart M, Stevenson M, Morrow J, Nelson J.
Neurodevelopment of children exposed in utero to lamotrigine, sodium
valproate and carbamazepine. Arch Dis Child 2011;96:643‑7.
69. Shallcross R, Bromley RL, Irwin B, Bonnett LJ, Morrow J, Baker GA, et al.
Child development following in utero exposure: Levetiracetam vs sodium
valproate. Neurology 2011;76:383‑9.
70. Nadebaum C, Anderson VA, Vajda F, Reutens DC, Barton S, Wood AG.
Language skills of school‑aged children prenatally exposed to antiepileptic
drugs. Neurology 2011;76:719‑26.
71. Bromley RL, Mawer G, Clayton‑Smith J, Baker GA; Liverpool and
Manchester Neurodevelopment Group. Autism spectrum disorders
following in utero exposure to antiepileptic drugs. Neurology
2008;71:1923‑4.
72. Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET,
Pedersen LH, et al. Prenatal valproate exposure and risk of autism
spectrum disorders and childhood autism. JAMA 2013;309:1696‑703.
73. Gentile S. Risks of neurobehavioral teratogenicity associated with prenatal
exposure to valproate monotherapy: A systematic review with regulatory
repercussions. CNS Spectr 2014;19:305‑15.
74. Piontek CM, Baab S, Peindl KS, Wisner KL. Serum valproate levels in 6
breastfeeding mother‑infant pairs. J Clin Psychiatry 2000;61:170‑2.
75. Wisner KL, Perel JM. Serum levels of valproate and carbamazepine in
breastfeeding mother‑infant pairs. J Clin Psychopharmacol 1998;18:167‑9.
76. Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ,
et al. Practice parameter update: Management issues for women with
epilepsy – Focus on pregnancy (an evidence‑based review): Vitamin K,
folic acid, blood levels, and breastfeeding: Report of the Quality
Indian J Psychiatry 57 (Supplement 2), July 2015
Standards Subcommittee and Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology and American
Epilepsy Society. Neurology 2009;73:142‑9.
77. American Academy of Pediatrics Committee on Drugs. The transfer
of drugs and other chemical agents into human milk. Pediatrics
2001;108:776‑89.
78. Jones KL, Lacro RV, Johnson KA, Adams J. Pattern of malformations
in the children of women treated with carbamazepine during pregnancy.
N Engl J Med 1989;320:1661‑6.
79. Rosa FW. Spina bifida in infants of women treated with carbamazepine
during pregnancy. N Engl J Med 1991;324:674‑7.
80. Frey B, Schubiger G, Musy JP. Transient cholestatic hepatitis in a
neonate associated with carbamazepine exposure during pregnancy and
breast‑feeding. Eur J Pediatr 1990;150:136‑8.
81. Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al.
Dose‑dependent risk of malformations with antiepileptic drugs: An analysis
of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol
2011;10:609‑17.
82. Merlob P, Mor N, Litwin A. Transient hepatic dysfunction in an infant of
an epileptic mother treated with carbamazepine during pregnancy and
breastfeeding. Ann Pharmacother 1992;26:1563‑5.
83. Scolnik D, Nulman I, Rovet J, Gladstone D, Czuchta D, Gardner HA,
et al. Neurodevelopment of children exposed in utero to phenytoin and
carbamazepine monotherapy. JAMA 1994;271:767‑70.
84. Gaily E, Kantola‑Sorsa E, Hiilesmaa V, Isoaho M, Matila R, Kotila M, et al.
Normal intelligence in children with prenatal exposure to carbamazepine.
Neurology 2004;62:28‑32.
85. Chaudron LH, Jefferson JW. Mood stabilizers during breastfeeding: A
review. J Clin Psychiatry 2000;61:79‑90.
86. Eisenschenk S. Treatment with oxcarbazepine during pregnancy.
Neurologist 2006;12:249‑54.
87. Newport DJ, Stowe ZN, Viguera AC, Calamaras MR, Juric S, Knight B,
et al. Lamotrigine in bipolar disorder: Efficacy during pregnancy. Bipolar
Disord 2008;10:432‑6.
88. Cunnington M, Tennis P; International Lamotrigine Pregnancy Registry
Scientific Advisory Committee. Lamotrigine and the risk of malformations
in pregnancy. Neurology 2005;64:955‑60.
89. Holmes LB, Baldwin EJ, Smith CR, Habecker E, Glassman L, Wong SL,
et al. Increased frequency of isolated cleft palate in infants exposed to
lamotrigine during pregnancy. Neurology 2008;70 (22 Pt 2):2152‑8.
90. Dolk H, Jentink J, Loane M, Morris J, de Jong‑van den Berg LT; EUROCAT
Antiepileptic Drug Working Group. Does lamotrigine use in pregnancy
increase orofacial cleft risk relative to other malformations? Neurology
2008;71:714‑22.
91. Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for
pregnant patients with bipolar disorder. Am J Psychiatry 2013;170:1240‑7.
92. Polepally AR, Pennell PB, Brundage RC, Stowe ZN, Newport DJ,
Viguera AC, et al. Model‑based lamotrigine clearance changes during
pregnancy: Clinical implication. Ann Clin Transl Neurol 2014;1:99‑106.
93. Mackay FJ, Wilton LV, Pearce GL, Freemantle SN, Mann RD. Safety of
long‑term lamotrigine in epilepsy. Epilepsia 1997;38:881‑6.
94. Rihtman T, Parush S, Ornoy A. Developmental outcomes at preschool
age after fetal exposure to valproic acid and lamotrigine: Cognitive, motor,
sensory and behavioral function. Reprod Toxicol 2013;41:115‑25.
95. Rambeck B, Kurlemann G, Stodieck SR, May TW, Jürgens U.
Concentrations of lamotrigine in a mother on lamotrigine treatment and
her newborn child. Eur J Clin Pharmacol 1997;51:481‑4.
96. Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: Pharmacokinetics
during delivery, in the neonate, and during lactation. Epilepsia
2000;41:709‑13.
97. Tomson T, Ohman I, Vitols S. Lamotrigine in pregnancy and lactation:
A case report. Epilepsia 1997;38:1039‑41.
98. Liporace J, Kao A, D’Abreu A. Concerns regarding lamotrigine and
breast‑feeding. Epilepsy Behav 2004;5:102‑5.
99. Page‑Sharp M, Kristensen JH, Hackett LP, Beran RG, Rampono J,
Hale TW, et al. Transfer of lamotrigine into breast milk. Ann Pharmacother
2006;40:1470‑1.
100. Newport DJ, Pennell PB, Calamaras MR, Ritchie JC, Newman M, Knight B,
et al. Lamotrigine in breast milk and nursing infants: Determination of
exposure. Pediatrics 2008;122:e223‑31.
101. Medical Economics. Physician‘s Desk Reference. Montvale, NJ: Medical
Economics; 2001.
102. Fadel RA, Sequeira RP, Abu‑Hijleh MF, Obeidat M, Salem AH. Effect of
prenatal administration of therapeutic doses of topiramate on ossification of
ribs and vertebrae in rat fetuses. Rom J Morphol Embryol 2012;53:321‑7.
103. Kwarta RF, Hulihan JF, Schmider J, Nye JS. Pregnancy outcomes in
topiramate‑treated women. Epilepsia 2006; 47 Suppl 4:119‑204.
104. Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, et al.
Topiramate in pregnancy: Preliminary experience from the UK Epilepsy
and Pregnancy Register. Neurology 2008;71:272‑6.
S321
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Grover and Avasthi: Mood stabilizers in pregnancy and lactation
105. Castilla‑Puentes R, Ford L, Manera L, Kwarta RF Jr, Ascher S, Li Q.
Topiramate monotherapy use in women with and without epilepsy:
Pregnancy and neonatal outcomes. Epilepsy Res 2014;108:717‑24.
106. Hernández‑Díaz S, Smith CR, Shen A, Mittendorf R, Hauser WA,
Yerby M, et al. Comparative safety of antiepileptic drugs during pregnancy.
Neurology 2012;78:1692‑9.
107. Mines D, Tennis P, Curkendall SM, Li DK, Peterson C, Andrews EB,
et al. Topiramate use in pregnancy and the birth prevalence of oral clefts.
Pharmacoepidemiol Drug Saf 2014;23:1017‑25.
108. Hernández‑Díaz S, Mittendorf R, Smith CR, Hauser WA, Yerby M,
Holmes LB, et al. Association between topiramate and zonisamide use
during pregnancy and low birth weight. Obstet Gynecol 2014;123:21‑8.
109. Veiby G, Daltveit AK, Engelsen BA, Gilhus NE. Fetal growth restriction and
birth defects with newer and older antiepileptic drugs during pregnancy.
J Neurol 2014;261:579‑88.
110. Margulis AV, Mitchell AA, Gilboa SM, Werler MM, Mittleman MA, Glynn RJ,
et al. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet
Gynecol 2012;207:405.e1‑7.
111. Ohman I, Vitols S, Tomson T. Pharmacokinetics of gabapentin during
delivery, in the neonatal period, and lactation: Does a fetal accumulation
occur during pregnancy? Epilepsia 2005;46:1621‑4.
112. Fujii H, Goel A, Bernard N, Pistelli A, Yates LM, Stephens S, et al.
Pregnancy outcomes following gabapentin use: Results of a prospective
comparative cohort study. Neurology 2013;80:1565‑70.
113. Goldstein DJ, Corbin LA, Fung MC. Olanzapine‑exposed pregnancies and
lactation: Early experience. J Clin Psychopharmacol 2000;20:399‑403.
114. Gentile S. Antipsychotic therapy during early and late pregnancy.
A systematic review. Schizophr Bull 2010;36:518‑44.
115. Brunner E, Falk DM, Jones M, Dey DK, Shatapathy CC. Olanzapine
in pregnancy and breastfeeding: A review of data from global safety
surveillance. BMC Pharmacol Toxicol 2013;14:38.
116. Levinson AJ, McKenna AK, Koren G, Zipursky RB. Pregnancy outcome in
women receiving atypical antipsychotic drugs: A prospective, multicentre,
controlled study. Schizophr Res 2003;60 Suppl 1:361.
117. Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and
delivery outcome. J Clin Psychopharmacol 2008;28:279‑88.
118. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S, Diav‑Citrin O,
et al. Pregnancy outcome of women using atypical antipsychotic drugs: A
prospective comparative study. J Clin Psychiatry 2005;66:444‑9.
119. Nagy A, Tényi T, Lénárd K, Herold R, Wilhelm F, Trixler M. Olanzapine and
pregnancy. Orv Hetil 2001;142:137‑8.
120. Kirchheiner J, Berghöfer A, Bolk‑Weischedel D. Healthy outcome
under olanzapine treatment in a pregnant woman. Pharmacopsychiatry
2000;33:78‑80.
121. Neumann NU, Frasch K. Olanzapine and pregnancy 2 case reports.
Nervenarzt 2001;72:876‑8.
122. Malek‑Ahmadi P. Olanzapine in pregnancy. Ann Pharmacother
2001;35:1294‑5.
123. Lim LM. Olanzapine and pregnancy. Aust N Z J Psychiatry 2001;35:856‑7.
124. Mendhekar DN, War L, Sharma JB, Jiloha RC. Olanzapine and pregnancy.
Pharmacopsychiatry 2002;35:122‑3.
125. Littrell KH, Johnson CG, Peabody CD, Hilligoss N. Antipsychotics during
pregnancy. Am J Psychiatry 2000;157:1342.
126. Vemuri MP, Rasgon NL. A case of olanzapine‑induced gestational diabetes
mellitus in the absence of weight gain. J Clin Psychiatry 2007;68:1989.
127. Aichhorn W, Yazdi K, Kralovec K, Steiner H, Whitworth S, Stuppaeck C.
Olanzapine plasma concentration in a newborn. J Psychopharmacol
2008;22:923‑4.
128. Friedman SH, Rosenthal MB. Treatment of perinatal delusional disorder:
A case report. Int J Psychiatry Med 2003;33:391‑4.
129. Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S,
et al. Atypical antipsychotic administration during late pregnancy: Placental
passage and obstetrical outcomes. Am J Psychiatry 2007;164:1214‑20.
130. Dervaux A, Ichou P, Pierrot F, Devianne F, Bavoux F. Olanzapine and
pregnancy [abstract]. Eur Psychiatry 2007;22:S110.
131. Sharma V, Smith A, Mazmanian D. Olanzapine in the prevention of
postpartum psychosis and mood episodes in bipolar disorder. Bipolar
Disord 2006;8:400‑4.
132. Kulkarni J, McCauley‑Elsom K, Marston N, Gilbert H, Gurvich C,
de Castella A, et al. Preliminary findings from the National Register
of Antipsychotic Medication in Pregnancy. Aust N Z J Psychiatry
2008;42:38‑44.
133. Yeshayahu Y. The use of olanzapine in pregnancy and congenital cardiac
and musculoskeletal abnormalities. Am J Psychiatry 2007;164:1759‑60.
134. Spyropoulou AC, Zervas IM, Soldatos CR. Hip dysplasia following a
case of olanzapine exposed pregnancy: A questionable association. Arch
Womens Ment Health 2006;9:219‑22.
135. Arora M, Praharaj SK. Meningocele and ankyloblepharon following in
utero exposure to olanzapine. Eur Psychiatry 2006;21:345‑6.
136. Prakash S, Chadda RK. Teratogenicity with olanzapine. Indian J Psychol
S322 Indian J Psychiatry 57 (Supplement 2), July 2015
Med 2014;36:91‑3.
137. Gati A, Trixler M, Tenyi T. Pregnancy and atypical antipsychotics. Eur
Neuropsychopharmacol 2001;11 Suppl 3:S247.
138. Gardiner SJ, Kristensen JH, Begg EJ, Hackett LP, Wilson DA, Ilett KF,
et al. Transfer of olanzapine into breast milk, calculation of infant drug
dose, and effect on breast‑fed infants. Am J Psychiatry 2003;160:1428‑31.
139. Kasper SC, Mattiuz EL, Swanson SP, Chiu JA, Johnson JT, Garner CO.
Determination of olanzapine in human breast milk by high‑performance
liquid chromatography with electrochemical detection. J Chromatogr B
Biomed Sci Appl 1999;726:203‑9.
140. Goldstein DJ, Corbin LA, Whlreich K. Olanzapine use during breast
feeding (abstract). Schizophr Res 2002;53 3 Suppl 1:185.
141. Croke S, Buist A, Hackett LP, Ilett KF, Norman TR, Burrows GD.
Olanzapine excretion in human breast milk: Estimation of infant exposure.
Int J Neuropsychopharmacol 2002;5:243‑7.
142. Ambresin G, Berney P, Schulz P, Bryois C. Olanzapine excretion into
breast milk: A case report. J Clin Psychopharmacol 2004;24:93‑5.
143. Gilad O, Merlob P, Stahl B, Klinger G. Outcome of infants exposed to
olanzapine during breastfeeding. Breastfeed Med 2011;6:55‑8.
144. Rosengarten H, Quartermain D. Effect of prenatal administration of
haloperidol, risperidone, quetiapine and olanzapine on spatial learning
and retention in adult rats. Pharmacol Biochem Behav 2002;72:575‑9.
145. MacKay FJ, Wilton GL, Pearce SN, Freemantle SH, Mann RD. The
safety of risperidone: A post‑marketing study on 7684 patients. Hum
Psychopharmacol Clin Exp 1998;13:423‑8.
146. Ratnayake T, Libretto SE. No complications with risperidone treatment
before and throughout pregnancy and during the nursing period. J Clin
Psychiatry 2002;63:76‑7.
147. Kato R, Sato J, Suzuki H. Anesthesia for cesarean section in a parturient
taking risperidone and haloperidol. Masui 2005;54:301‑3.
148. Kim SW, Kim KM, Kim JM, Shin IS, Shin HY, Yang SJ, et al. Use of long‑acting
injectable risperidone before and throughout pregnancy in schizophrenia.
Prog Neuropsychopharmacol Biol Psychiatry 2007;31:543‑5.
149. Dabbert D, Heinze M. Follow‑up of a pregnancy with risperidone
microspheres. Pharmacopsychiatry 2006;39:235.
150. Grover S, Avasthi A. Risperidone in pregnancy: A case of oligohydramnios.
German J Psychiatry 2004;7:56‑7.
151. Coppola D, Russo LJ, Kwarta RF Jr, Varughese R, Schmider J. Evaluating
the postmarketing experience of risperidone use during pregnancy:
Pregnancy and neonatal outcomes. Drug Saf 2007;30:247‑64.
152. McCauley‑Elsom K, Kulkarni J. Managing psychosis in pregnancy. Aust N
Z J Psychiatry 2007;41:289‑92.
153. Ghaffari N, Dossett E, Lee RH, Aghajanian P. Antipsychotics leading
to neuroleptic malignant syndrome in pregnancy. Obstet Gynecol
2012;119 (2 Pt 2):436‑8.
154. Hill RC, McIvor RJ, Wojnar‑Horton RE, Hackett LP, Ilett KF. Risperidone
distribution and excretion into human milk: Case report and estimated infant
exposure during breast‑feeding. J Clin Psychopharmacol 2000;20:285‑6.
155. Ilett KF, Hackett LP, Kristensen JH, Vaddadi KS, Gardiner SJ, Begg EJ.
Transfer of risperidone and 9‑hydroxyrisperidone into human milk. Ann
Pharmacother 2004;38:273‑6.
156. Aichhorn W, Stuppaeck C, Whitworth AB. Risperidone and breast‑feeding.
J Psychopharmacol 2005;19:211‑3.
157. Twaites BR, Wilton LV, Shakir SA. The safety of quetiapine: Results
of a post‑marketing surveillance study on 1728 patients in England.
J Psychopharmacol 2007;21:392‑9.
158. Balke LD. Quetiapine is Effective in the Treatment of Bipolar Affective
Disorder during Pregnancy. Poster Session Presented at: 7th World
Congress of Biological Psychiatry; July 1‑6, 2001; Berlin, Germany.
159. Texnyi T, Trixler M, Kerestes Z. Quetiapine and pregnancy [letter]. Am J
Psychiatry 2002;159:674.
160. Pace A, D’Agostino F. Quetiapine in pregnancy: A case report. G Ital Ostet
Ginecol 2003;25:381‑5.
161. Lee A, Giesbrecht E, Dunn E, Ito S. Excretion of quetiapine in breast milk.
Am J Psychiatry 2004;161:1715‑6.
162. Gentile  S. Quetiapine‑fluvoxamine combination during pregnancy and
while breastfeeding. Arch Womens Ment Health 2006;9:158‑9.
163. Kruninger U, Meltzer V, Hiemke C, Herpich S. Pregnancy and lactation
under treatment with quetiapine. Psychiatr Prax 2007;34 Suppl: 75‑6.
164. Cabuk D, Sayin A, Derinöz O, Biri A. Quetiapine use for the treatment
of manic episode during pregnancy. Arch Womens Ment Health
2007;10:235‑6.
165. Kaya DF, Sayin A, Biri A. Quetiapine use in manic episode during
pregnancy: A case report. 1 Eur Psychiatry 2007;22:S166.
166. Frayne J, Nguyen T, Kohan R, De Felice N, Rampono J.The comprehensive
management of pregnant women with major mood disorders: A case study
involving phenelzine, lithium, and quetiapine. Arch Womens Ment Health
2014;17:73-5.
167. Grover S, Madan R. Successful use of quetiapine in two successive
pregnancies. J Neuropsychiatry Clin Neurosci 2012;24:E38.
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Grover and Avasthi: Mood stabilizers in pregnancy and lactation
168. Tényi T, Nagy Á, Herold R, Fekete S. Extended release quetiapine
fumarate and pregnancy. Neuropsychopharmacol Hung 2013;15:49‑50.
169. Rampono J, Kristensen JH, Ilett KF, Hackett LP, Kohan R. Quetiapine and
breast feeding. Ann Pharmacother 2007;41:711‑4.
170. Peitl MV, Petric D, Peitl V. Ziprasidone as a possible cause of cleft palate
in a newborn. Psychiatr Danub 2010;22:117‑9.
171. Werremeyer A. Ziprasidone and citalopram use in pregnancy and lactation
in a woman with psychotic depression. Am J Psychiatry 2009;166:1298.
172. Aripiprazole Prescribing Information. Bristol‑Myers Squibb Pharmaceuticals/
Otsuka Pharmaceutical Co Ltd.; 2003.
173. Mendhekar DN, Sunder KR, Andrade C. Aripiprazole use in a pregnant
schizoaffective woman. Bipolar Disord 2006;8:299‑300.
174. Mendhekar DN, Sharma JB, Srilakshmi P. Use of aripiprazole during
late pregnancy in a woman with psychotic illness. Ann Pharmacother
2006;40:575.
175. Doulgeraki G, Karadima D, Kalogiratos D, Grekiotis A, Magoula K.
Pregnancy, aripiprazole and psychotherapy. Eur Psychiatry 2007;22:S206.
176. Mervak B, Collins J, Valenstein M. Case report of aripiprazole usage
during pregnancy. Arch Womens Ment Health 2008;11:249‑50.
177. Wichman CL. Atypical antipsychotic use in pregnancy: A retrospective
review. Arch Womens Ment Health 2009;12:53‑7.
178. Lutz UC, Hiemke C, Wiatr G, Farger G, Arand J, Wildgruber D. Aripiprazole
in pregnancy and lactation: A case report. J Clin Psychopharmacol
2010;30:204‑5.
179. Gentile S, Tofani S, Bellantuono C. Aripiprazole and pregnancy: A case
report and literature review. J Clin Psychopharmacol 2011;31:531‑2.
180. Watanabe N, Kasahara M, Sugibayashi R, Nakamura T, Nakajima K,
Watanabe O, et al. Perinatal use of aripiprazole: A case report. J Clin
Psychopharmacol 2011;31:377‑9.
181. Nguyen T, Teoh S, Hackett LP, Ilett K. Placental transfer of aripiprazole.
Aust N Z J Psychiatry 2011;45:500‑1.
182. Widschwendter CG, Hofer A. Aripiprazole use in early pregnancy: A case
report. Pharmacopsychiatry 2012;45:299‑300.
183. Derganc M, Savs AP. The use of aripiprazole in pregnancy: A case report.
Abstract P002 at the 21st European Congress of Psychiatry EPA, April 6‑9,
2013; Nice, France.
184. Windhager E, Kim SW, Saria A, Zauner K, Amminger PG, Klier CM.
Perinatal use of aripiprazole: Plasma levels, placental transfer, and child
outcome in 3 new cases. J Clin Psychopharmacol 2014;34:637‑41.
185. Waldman MD, Safferman AZ. Pregnancy and clozapine. Am J Psychiatry
1993;150:168‑9.
186. Barnas C, Bergant A, Hummer M, Saria A, Fleischhacker WW. Clozapine
concentrations in maternal and fetal plasma, amniotic fluid, and breast
milk. Am J Psychiatry 1994;151:945.
187. Dickson RA, Hogg L. Pregnancy of a patient treated with clozapine.
Psychiatr Serv 1998;49:1081‑3.
188. Di Michele V, Ramenghi L, Sabatino G. Clozapine and lorazepam
administration in pregnancy. Eur Psychiatry 1996;11:214.
189. Stoner SC, Sommi RW Jr, Marken PA, Anya I, Vaughn J. Clozapine use in
two full‑term pregnancies. J Clin Psychiatry 1997;58:364‑5.
190. Tényi T, Trixler M, Vereczkey G, Dorka A. Use of clozapine during
pregnancy. Orv Hetil 1994;135:1967‑9.
191. Gupta N, Grover S. Safety of clozapine in 2 successive pregnancies. Can
J Psychiatry 2004;49:863.
192. Sethi S. Clozapine in pregnancy. Indian J Psychiatry 2006;48:196‑7.
193. Dev V, Knapp P. The side effects and safety of clozapine. Rev Contemp
Pharmacother 1995;6:197‑208.
194. Yogev Y, Ben‑Haroush A, Kaplan B. Maternal clozapine treatment and
decreased fetal heart rate variability. Int J Gynaecol Obstet 2002;79:259‑60.
195. Coston AL, Hoffmann P, Equy V, Sergent F, Vidal C. Fetal heart rate
variability and clozapine treatment. Gynecol Obstet Fertil 2012;40:549‑52.
Indian J Psychiatry 57 (Supplement 2), July 2015
196. Moreno‑Bruna MD, de Montgolfier I, Chabaud M, Dommergues M. Case
report: Neonatal delayed peristalsis after in‑utero exposure to clozapine.
Arch Pediatr 2012;19:913‑6.
197. Mendhekar DN. Possible delayed speech acquisition with clozapine
therapy during pregnancy and lactation. J Neuropsychiatry Clin Neurosci
2007;19:196‑7.
198. Baker RW, Chengappa KN. Gastroesophageal reflux as a possible result
of clozapine treatment. J Clin Psychiatry 1998;59:257.
199. Mendhekar DN, Sharma JB, Srivastava PK, War L. Clozapine and
pregnancy. J Clin Psychiatry 2003;64:850.
200. Klys M, Rojek S, Rzepecka‑Wozniak E. Neonatal death following clozapine
self‑poisoning in late pregnancy: An unusual case report. Forensic Sci Int
2007;171:e5‑10.
201. Novikova N, Chitnis M, Linder V, Hofmeyr GJ. Atypical
antipsychotic (clozapine) self‑poisoning in late pregnancy presenting
with absent fetal heart rate variability without acidosis and delayed
peristalsis in the newborn baby: A case report. Aust N Z J Obstet Gynaecol
2009;49:442‑4.
202. Iqbal MM, Sobhan T, Ryals T. Effects of commonly used benzodiazepines
on the fetus, the neonate, and the nursing infant. Psychiatr Serv
2002;53:39‑49.
203. Saxén I, Saxén L. Letter: Association between maternal intake of diazepam
and oral clefts. Lancet 1975;2:498.
204. Entman SS, Vaughn WK. Lack of relation of oral clefts to diazepam use in
pregnancy. N Engl J Med 1984;310:1121‑2.
205. Czeizel A. Letter: Diazepam, phenytoin, and aetiology of cleft lip and/or
cleft palate. Lancet 1976;1:810.
206. Saxén I. Epidemiology of cleft lip and palate. An attempt to rule out chance
correlations. Br J Prev Soc Med 1975;29:103‑10.
207. Czeizel A, Lendvay A. In utero exposure to benzodiazepines [letter].
Lancet 1987;1:628.
208. Shiono PH, Mills JL. Oral clefts and diazepam use during pregnancy.
N Engl J Med 1984;311:919‑20.
209. Czeizel A. Endpoints of reproductive dysfunction in an experimental
epidemiological model: Self‑poisoned pregnant women. In: Chambers PL,
Gehring P, Sakai F, editors. New Concepts and Developments in
Toxicology. Amsterdam: Elsevier; 1986.
210. Czeizel A, Pázsy A, Pusztai J, Nagy M. Aetiological monitor of congenital
abnormalities: A case‑control surveillance system. Acta Paediatr Hung
1983;24:91‑9.
211. Yonkers KA, Wisner KL, Stowe Z, Leibenluft E, Cohen L, Miller L, et al.
Management of bipolar disorder during pregnancy and the postpartum
period. Am J Psychiatry 2004;161:608‑20.
212. Curtis  V. Women are not the same as men: Specific clinical
issues for female patients with bipolar disorder. Bipolar Disord
2005;7 Suppl 1:16‑24.
213. Delgado‑Escueta AV, Janz D. Consensus guidelines: Preconception
counseling, management, and care of the pregnant woman with epilepsy.
Neurology 1992;42 4 Suppl 5:149‑60.
214. Weinstein MR. Lithium treatment of women during pregnancy and in the
post‑delivery period. In: Johnson FN, editor. Handbook of Lithum theraphy.
Park Pren: Baltimore University; 1980. p. 421‑9.
215. Stewart DE, Klompenhouwer JL, Kendell RE, van Hulst AM. Prophylactic
lithium in puerperal psychosis. The experience of three centres. Br J
Psychiatry 1991;158:393‑7.
216. Cohen LS, Sichel DA, Robertson LM, Heckscher E, Rosenbaum JF.
Postpartum prophylaxis for women with bipolar disorder. Am J Psychiatry
1995;152:1641‑5.
Source of Support: Nil, Conflict of Interest: None declared
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REVIEW ARTICLE

Antidepressants, anxiolytics, and hypnotics in pregnancy and lactation

Daya Ram, S. Gandotra1
Director, Central Institute of Psychiatry, 1Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi,
Jharkhand, India

ABSTRACT

Aims: Untreated perinatal depression and anxiety disorders are known to have significant negative impact on both maternal
and fetal health. Dilemmas still remain regarding the use and safety of psychotropics in pregnant and lactating women
suffering from perinatal depression and anxiety disorders. The aim of the current paper was to review the existing evidence
base on the exposure and consequences of antidepressants, anxiolytics, and hypnotics in women during pregnancy and
lactation and to make recommendations for clinical decision making in management of these cases.
Materials and Methods: We undertook a bibliographic search of Medline/PubMed  (1972 through 2014), Science
Direct  (1972 through 2014), Archives of Indian Journal of Psychiatry databases was done. References of retrieved
articles, reference books, and dedicated websites were also checked.
Results and Conclusions: The existing evidence base is extensive in studying multiple outcomes of the antidepressant
or anxiolytic exposure in neonates, and some of the findings appear conflicting. Selective serotonin reuptake inhibitors
are the most researched antidepressants in pregnancy and lactation. The available literature is criticized mostly on the
lack of rigorous well designed controlled studies as well as lacunae in the methodologies, interpretation of statistical
information, knowledge transfer, and translation of information. Research in this area in the Indian context is strikingly
scarce. Appropriate risk‑benefit analysis of untreated mental illness versus medication exposure, tailor‑made to each
patient’s past response and preference within in the context of the available evidence should guide clinical decision
making.

Key words: Antidepressants, anxiolytics, birth outcomes, lactation, pregnancy, psychotropic

INTRODUCTION psychotropic medications to the fetus and mother must be

Drug management of pregnant and breastfeeding women
afflicted with comorbid psychiatric disorders offers a potential
challenge for management. Perinatal psychiatry is emerging
as an important consultation subspecialty considering a
growing number of pregnancies in women with more severe
and chronic mental disorders and up to one‑third of women
being exposed to psychotropics during pregnancy.[1]
A risk‑benefit assessment in terms of risks of untreated
psychiatric symptoms against those due to adverse effects of
considered.[2] This risk may present as spontaneous abortion
or premature labor, toxicity or withdrawal symptoms to the
fetus, morphological teratogenicity, and risk of breastfeeding
while on psychotropic. Psychiatric illness impairs the level
of functioning and ability for the woman who is pregnant
to care for herself and fetus. It may lead to malnutrition,
refusal or inability to participate in prenatal care, premature
delivery, intended harm to the fetus or neonate through
suicide or neonaticide, precipitous delivery or high‑risk
delivery.[3‑8]

Access this article online

Address for correspondence: Dr. Sachin Gandotra,
Mental Health Foundation St. Maarten, Dutch Caribbean, Quick Response Code
Ex‑Faculty Central Institute of Psychiatry, Ranchi, Jharkhand, India. Website:
E‑mail: sachincip@gmail.com www.indianjpsychiatry.org

How to cite this article: Ram D, Gandotra S. Antidepressants, DOI:

anxiolytics, and hypnotics in pregnancy and lactation. Indian J
10.4103/0019-5545.161504
Psychiatry 2015;57:354-71.

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 Ram and Gandotra: Psychotropics in pregnancy and lactation
The purpose of this paper was to present a complete review of
the literature and guide clinical decision making for the use of
antidepressants, anxiolytics, and hypnotics during the pregnant
state and postpartum during lactation. A bibliographic search
of Medline/PubMed (1975 through 2014), Science Direct (1975
through 2014), Archives of Indian Journal of Psychiatry
databases was done. References of retrieved articles, reference
books, and dedicated websites were also checked. The paper
will present the usage of these psychotropics in two sections,
one devoted to the state of pregnancy, and the other to the
postpartum state, primarily lactation.
SECTION 1
Issues related to psychotropic drug use in pregnancy
Pharmacokinetic changes in pregnancy
Adverse drug events are often linked to the pharmacokinetic
variations in maternal, placental, or fetal variables.[9]
Physiological changes in maternal absorption include
slower gastric emptying, increased mucus production,
decreased acid secretion. There is increased intravascular
and extravascular volume of distribution, decreased plasma
binding concentration, and albumin binding capacity.
Microsomal liver enzymes get induced by circulating steroids,
and there is biliary stasis. Glomerular filtration rate and renal
blood flow are increased. Finally, nonionized, lipid‑soluble,
low molecular weight drugs have a better transplacental
absorption. Vulnerability factors for the fetus include small
total plasma volume, decreased albumin with increased
levels of free drugs, decreased hepatic enzyme formation,
decreased GFR, and immature blood‑brain barrier.[9]
The change in psychotropic dose can be complex depending
on the trimester(s) of exposure. For example, to maintain
serum levels within the therapeutic range, particularly in the
third trimester, the dose of tricyclic antidepressant (TCA)
must be increased 1.6 times the mean dose required
when the patients are not pregnant.[10] In addition, some
drugs tend to concentrate in the fetus, and their effects
may be prolonged even after delivery.[10] It is advisable
to monitor the effectiveness of treatment throughout
pregnancy to achieve the lowest effective dose of any
agent, and further, to discontinue psychoactive drug(s) by
tapering the dose, especially for antianxiety drugs, 2 weeks
before the estimated delivery date to minimize neonatal
effects. However, in patients with the severe disease, it
may precipitate discontinuation syndromes or recurrence
of signs and symptoms. Consultation liaison with other
physicians (e.g., psychiatrist, pediatrician, or obstetrician),
is always advisable.[8]
Why are we so less informed about psychotropic drug
usage in pregnancy?
Case reports or retrospective cohort epidemiologic studies
happen to be the primary source for risk estimation
of psychotropic drug exposure during pregnancy. The
Indian J Psychiatry 57 (Supplement 2), July 2015
bottlenecks in such evidence base include possible reporting
bias and the many confounding variables, such as lack of
accounting for nutritional and health status; maternal age;
use of alcohol, tobacco, or illicit drugs; environmental
toxins; history of miscarriages and stillbirths; genetic
history; use of multiple drugs including nonprescription
drugs; gestational age at time of drug exposure; compliance;
total dose; and the effects of the psychiatric illness or other
illnesses present.
Prospective, randomized, and well‑controlled investigational
studies[11] on the risks of exposure to psychoactive drugs
during pregnancy are neither feasible nor ethical. Doses
used in prehuman animal trials do not reliably predict the
human response.[8]
Overestimation of the fetal risk to a specific drug or a
combination of medications is possible. Case reports do not
establish causation.
It is necessary to distinguish between the natural prevalence
rate and the rate at which the defect occurs in a population
and the additional risk potentially attributable to a drug.
Studies of large populations are required, yet usually
unattainable, to determine the relative risk from specific
potential teratogens.
Assessing neurobehavioral effects from in utero exposure
to centrally acting drugs, especially beyond the immediate
neonatal period should consider the dose, offspring’s age
and gender, and behavior test system.[12]
In view of such events[13] as the thalidomide crisis in the
1960’s and the teratogenic effects of diethylstilbestrol in
1979, US Food and Drug Administration (FDA) developed
strict guidelines regarding drug labeling,[14] use of
medications in pregnancy with safety parameters before it
was marketed [Table 1]. Some recommend that FDA ratings
be replaced by narrative statements that summarize and
interpret available data regarding hazards of developmental
toxicity and provide estimates of teratogenic risk.
In the backdrop of these limitations, we proceed to share
the available data in usage of some specific categories of
psychotropic agents.
Antidepressant medications in pregnancy
Antidepressant exposure during pregnancy may manifest in
terms of one of the four outcomes:[15]
Pregnancy loss due to miscarriage
Psychotropic drug exposure during pregnancy might lead to
miscarriage or abortions.
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
Table 1: FDA use‑in‑pregnancy ratings
Category Interpretation
A Controlled studies show no risk. Adequate, well‑controlled studies
in pregnant women have failed to demonstrate risk to the fetus
B No evidence of risk in humans. Either animal findings show risk,
but human findings do not, or if no adequate human studies have
been done, animal findings are negative
C Risk cannot be ruled out. Human studies are lacking, and animal
studies are either positive for fetal risk or lacking as well.
However, potential benefits may justify the potential risk
D Positive evidence of risk. Investigational or postmarketing data
show risk to the fetus. Nevertheless, potential benefits may
outweigh the potential risk
X Contraindicated in pregnancy. Studies in animals or humans, or
investigational or postmarketing reports have shown fetal risk that
clearly outweighs any possible benefit to the patient
FDA – Food and Drug Administration
Risk of teratogenesis
Of the major birth defects studied in association with
antidepressant use, omphalocele occurs in 1 per 5386
births, gastroschisis occurs in 1 per 2229, anencephaly 1 in
every 4859, and craniosynostosis in 4–10 per 10,000 births
in the general population.[16] A teratogen is defined as an
agent that interferes with the process of organogenesis and
produces some type of organ malformation or dysfunction.[15]
Exposure to a toxic agent before 2 weeks of gestation is
not associated with congenital malformations.[17] For each
organ or organ system, there exists a critical period during
which development takes place and may be susceptible to
the effects of a teratogen.[18]
Neonatal toxicity
Refers to a spectrum of physical and behavioral symptoms
observed in the acute neonatal period that are attributed to
drug exposure at or near the time of delivery.
Long‑term neurobehavioral sequelae
Manifest as insults that occur after neural tube
closure produce changes in behavior and function, as
opposed to gross structural abnormalities. Behavioral
teratogenesis refers to the potential of a psychotropic drug
administered prenatally to cause long‑term neurobehavioral
sequelae.[15]
During gestation, the degree of fetal antidepressant
exposure is largely dictated by the placental passage of
the medication. Although formal data are limited, it is
assumed that all antidepressants cross the placenta.[19]
Transfer across the placenta has been grouped into three
categories: (1) Type I, complete transfer. These medications
rapidly equilibrate in concentration between the maternal
and fetal compartments; (2) Type II, excessive transfer. The
umbilical cord concentrations are greater than maternal
serum concentrations; (3) Type III, incomplete transfer. The
umbilical cord concentration is less than maternal serum
concentration.[20]
S356 Indian J Psychiatry 57 (Supplement 2), July 2015
Drugs included
Iron
Clozapine, fluoxetine, sertraline, paroxetine, bupropion, zolpidem
Haloperidol, chlorpromazine, olanzapine, risperidone, quetiapine, amitriptaline,
imipramine, desipramine, nortriptiline, duloxetine, fluvoxamine, escitalopram,
venlafaxine, mirtazapine, lamotrigine, topiramate, trihexyphenidyl
Lithium, carbamazepine, diazepam, clonazepam, lorazepam, alprazolam
Valproate, thalidomide
Preliminary data in terms of case reports[21,22] exist that
medication levels decrease as the pregnancy progresses.
Other case reports[21‑26] focusing on the disparity between
the placental passage of TCA and selective serotonin
reuptake inhibitor (SSRI) based on in vivo case series and
ex vivo perfusion data yield controversial results. Whether
or not such exposure accounts for purported withdrawal
symptoms in the neonate is unclear.
Lately research evidence is being generated to ascertain
the link between SSRI pharmacogenetics and specific fetal/
neonatal outcomes.[27] The scientific inquiry is toward
individual gene sequencing may provide more knowledge
for safe maternal pharmacotherapies on an individualized
basis and therefore contributing to better stratify the risk
for the possible adverse neonatal outcome.
Tricyclic antidepressants
Pregnancy loss
The available data do not seem to have addressed the issue
of miscarriage due to the prenatal exposure to TCAs. In
general, most case reports[8] do not support an increased
risk of miscarriage following antidepressant use, but these
assess SSRI risk than that of TCA.
Teratogenic potential
Three prospective and more than 10 retrospective
studies[28‑31] have examined the risk of organ dysgenesis
in over 400 cases of first‑trimester exposure to TCAs.
Pooled data from these studies defy the findings of early
case reports suggesting a possible association between
first‑trimester exposure to TCAs and limb malformation.
Among the TCAs, desipramine and nortriptyline are
preferred because they are less anticholinergic and the
least likely to exacerbate orthostatic hypotension that
occurs during pregnancy.[15]
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
Neonatal toxicity
A TCA withdrawal syndrome with characteristic symptoms
of jitteriness, irritability, and less commonly, the seizure
has been observed.[32‑36] Withdrawal seizures have been
reported only with clomipramine.[32‑36] These symptoms
have been given the rubric of postneonatal adaptation
syndrome (PNAS). More recent reports have indicated that
of all the infants exposed to TCAs in utero, 20–50% develop
PNAS,[37‑39] In addition, transient neonatal toxicity attributed
to the anticholinergic effect of TCAs, including symptoms
of functional bowel obstruction and urinary retention, have
also been reported.[40‑42]
Neurobehavioral sequelae
Animal studies[43,44] demonstrate changes in behavior and
neurotransmitter function after prenatal exposure to
various psychotropic agents. The findings are difficult to
extrapolate to humans. The data regarding neurobehavioral
abnormalities following fluoxetine or TCAs exposure
during pregnancy are limited but reassuring. In a landmark
study, Nulman et al.[45] followed a cohort of children
up to preschool age who had been exposed to either
TCAs (n = 80) or fluoxetine (n = 55) during pregnancy (most
commonly during the first trimester) and compared these
subjects to a cohort of nonexposed controls (n = 84).
No significant differences in IQ, temperament, behavior,
reactivity, mood, distractibility, or activity level between
exposed and nonexposed children were observed. A more
recent report[46] from the same group followed a cohort of
children exposed to fluoxetine (n = 40) or TCAs (n = 47)
for the entire duration of the pregnancy and yielded similar
results. Simon et al.[47] conducted a long‑term case‑control
study that followed prenatal and developmental outcomes
of 209 infants exposed to TCA during in utero and found
results comparable to normal controls and even better than
for SSRI exposed group in some aspects. However, these
data are preliminary and further investigation into the
long‑term neurobehavioral effects of prenatal exposure to
antidepressants, as well as other psychotropic medications,
is warranted.
Selective serotonin reuptake inhibitor
Pregnancy loss
The evidence regarding the safety of SSRIs in pregnancy has
shown a change in the findings in the literature reported
before and after 2005.[39] Majority of the studies done before
2005[48‑51] report no significant association of poor fetal
or pregnancy outcomes with SSRIs especially fluoxetine
use, however, the literature reported after 2005[52‑55] have
unearthed some such associations. However, several
reports[12,56] describe small increases in rates of spontaneous
abortion among women treated during the first trimester
of pregnancy with SSRIs or dual action agents (selective
norepinephrine reuptake inhibitors [SNRIs]). This shift in
literature has been attributed to limitations in statistical
inference in rates of miscarriage between exposed
Indian J Psychiatry 57 (Supplement 2), July 2015
and nonexposed women, insufficient statistical power,
confounding by the depression itself that may contribute
to increasing risk of spontaneous abortion, reporting bias
of miscarriage when some subjects might have opted for
termination of pregnancy.[39,57]
Teratogenic potential
Data reported earlier[49,51,57] have evaluated rates of congenital
malformation in approximately 1100 fluoxetine‑exposed
infants and did not suggest an increased risk of congenital
malformations with in utero exposure to SSRIs. Chambers
et al.[49] noted an increase in risk for multiple minor
malformations in fluoxetine‑exposed infants. This study
had several methodological limitations as, unexplained
significant difference in terms of important variables, such
as age, presence of psychiatric illness, and exposure to
other medications between the fluoxetine‑exposed women
and control groups, nonblinded raters were used, and
selection bias.[58,59] The post marketing surveillance registry
data[30,47] from the manufacturer of fluoxetine and two other
retrospective studies support these findings. These data
collected from over 2500 cases indicate no increase in the
risk of major congenital malformation in fluoxetine‑exposed
infants. A meta‑analyses[48] combining studies with
exposures to TCAs and SSRIs did not demonstrate an
increase in the risk of congenital malformation. One
prospective study[60] of 531 infants with first‑trimester
exposure to SSRIs (mostly citalopram, n = 375) did not
demonstrate an increased risk of organ malformation. In
a retrospective study[61] of 63 infants with first‑trimester
exposure to paroxetine, no increase in teratogenic risk
was observed. In a prospective, controlled cohort study,
Kulin et al.[56] reported on outcomes in neonates exposed
in utero to fluvoxamine (n = 26), paroxetine (n = 97),
and sertraline (n = 147). Pregnancy outcomes did not
differ between the exposed and nonexposed groups in
terms of risk for congenital malformation. Birth weights
and gestational age were similar in both groups. Though
this information on these SSRIs is reassuring, one of the
major limitations of this study is that the analysis grouped
the three antidepressants together versus analyzing each
antidepressant separately for teratogenic risk.
More recent data reports findings which are inconsistent
and make it difficult to implicate individual SSRIs associated
with risk of congenital malformations. Two studies Alwan
et al.[62] and Louik et al.[63] have linked the use of SSRI drugs
to rare malformations, but both studies have limitations of
recall bias and a high rate of nonresponders.
Some studies such as by Wogelius et  al.[64] identified
malformations from discharge diagnoses in women with
and without intrauterine SSRI exposure. Limitations in this
study included surveillance bias and overestimation of risks
due to the identification of less serious malformations.
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
Isolated reports have found malformation risks with some
specific SSRI exposure in utero. These include hypertrophic
stenosis,[65] congenital heart defects, and other major
abnormalities[66‑69] with fluoxetine, omphalocele,[63,69‑71]
and cardiac septal defects[63,69,71] with sertraline, and
omphalocele[63,69‑71] congenital heart defects,[63,69,71] and
neural tube defects[68] with citalopram. Other studies
however, have not suggested an association between
fluoxetine,[63,64,69‑77] sertraline,[54,66,72‑77] or citalopram[66,73‑75,77]
and major congenital abnormalities. While the data are very
limited, escitalopram has not been associated with risk of
major malformation.[63,68,75,78]
Paroxetine has emerged as one of the most notorious
SSRIs in terms of reported risks of malformation and
recommendations in pregnancy. Strings of evidence have
accumulated in this respect with a small study performed
by GlaxoSmithKline in 2005[79] which suggested an increase
in cardiac malformations in infants exposed to paroxetine
in utero compared with controls. Thereafter, multiple
studies[54,62,65,66,68,72,80,81] although not all[67,74] have found an
association between prenatal paroxetine exposure and
an increased risk of congenital malformations (atrial and
ventricular septal defects), yet the causality and magnitude
of that risk are unclear. A recent meta‑analysis found that
paroxetine was associated with a 1.7‑fold risk increase of
cardiac malformation.[82] This finding was criticized due
to the limitations in the methodology of the published
studies.[83] Another meta‑analysis that examined 37 studies
from January of 1992 to September 2008, linking an increased
risk of major congenital malformations with paroxetine
exposure concluded that first trimester paroxetine exposure
is associated with an increased prevalence of combined
cardiac defects (prevalence odds ratio (POR) =1.46%;
95% confidence interval [CI]: 1.17–1.82) and aggregated
defects (POR = 1.24; 95% CI: 1.08–1.43).[39,81]
To overcome the limitation of the inadequate power of
individual studies, evidence from meta‑analysis might
be more reliable. Five meta‑analyses have investigated
the risk for major malformations in association with
antidepressant use during pregnancy. Four of these studies
found no statistically significant increased risk of major
malformations in the first trimester of pregnancy.[48,84‑86]
The fifth meta‑analysis found an increased risk of cardiac
malformations in infants exposed to paroxetine in the
first‑trimester.[82]
Neonatal toxicity
Case reports[87‑90] and prospective studies[47,49] have
described perinatal complications in fluoxetine exposed
infants, including poor neonatal adaptation, respiratory
distress, feeding problems, and jitteriness. Several other
studies[46,50,51,56] have not observed perinatal distress in
infants exposed to fluoxetine. Limitations of these reports
are that the effects of an antenatal mood disorder on
S358 Indian J Psychiatry 57 (Supplement 2), July 2015
the neonatal outcome are not taken into account given
the absence of measurement of maternal mood across
pregnancy. Case reports[91‑96] of neonatal withdrawal in
neonates exposed to paroxetine have been published. In a
prospectively ascertained sample[91] of 55 neonates exposed
to paroxetine proximate to delivery (dose range 10–60 mg,
median 20 mg), 22% (n = 12) had complications necessitating
intensive treatment. The most common symptoms included
respiratory distress (n = 9), hypoglycemia (n = 2), and
jaundice (n = 1), all of which resolved over 1–2 weeks
without specific intervention. Other prospective studies[97‑101]
have similar findings. While the available evidence is
conflicting, the overall data suggest that PNAS can occur in
neonates exposed to SSRIs and SNRIs, yet have most often
been reported after exposure to paroxetine, fluoxetine,
and venlafaxine.[39] Furthermore, it is crucial to investigate
other factors that modulate vulnerability to neonatal toxicity
(e.g., prematurity and low birth weight).[20]
Another major association of in utero SSRI exposure is
the risk of persistent pulmonary hypertension of the
newborn (PPHN). Various prospective and case‑control
studies[49,102‑106] have implicated an association with
multiple SSRIs with the risk of development of PPHN.
These include fluoxetine, paroxetine, TCAs, monoamine
oxidase inhibitors (MAOI) and SNRIs. In 2006, based on data
reported at that time, the FDA published a Public Health
Advisory regarding an increased risk of PPHN associated
with the use of SSRIs after the 20th week of pregnancy. This
was repealed in December 2011 when the FDA released a
Drug Safety Communication[107] which stated that there is
insufficient evidence that antidepressant exposure during
pregnancy causes PPHN. This is a result of the current
evidence base which has reported either a small association
between PPHN and maternal antidepressant use during
pregnancy or no association.[39]
Neurobehavioral sequelae
One study[46] evaluated the long‑term sequelae of exposure
to fluoxetine during pregnancy and found no effect on
cognition, language development, or the treatment of
preschool and early‑school children. Another small study[108]
followed up 31 infants exposed in utero to different SSRIs up
to 6–40 months found lower scores in Bayley psychomotor
development index. A more recent study[109] aiming to
explore whether infants’ language development is altered
by prenatal exposure to SRIs and whether such effects differ
from exposure to maternal mood disturbances were studied
at 36 week gestation (while still in utero) on a consonant and
vowel discrimination task and at 6 and 10 months of age on
a nonnative speech and visual language discrimination task.
Whereas the control infants (non‑SRI‑treated mothers with
little or no depression) responded as expected (success
at 6 months and failure at 10 months) the SRI‑exposed
infants (mothers depressed and treated with SSRI) failed
to discriminate the language differences at both age and
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
the depressed‑only infants (Mothers depressed but non
SSRI treated) succeeded at 10 months instead of 6 months.
Fetuses at 36‑week gestation in the control condition
performed as expected, with a response on vowel but
not consonant discrimination, whereas the SRI‑exposed
fetuses showed accelerated perceptual development by
discriminating both vowels and consonants. The authors
concluded that prenatal depressed maternal mood and SRI
exposure were found to shift developmental milestones
bi‑directionally on infant speech perception tasks.
More recent studies[110] are linking in utero exposure to SSRI
and MAOI to an increased risk of autism spectrum disorders,
particularly without intellectual disability. These data
come from a Swedish Stockholm county population‑based
nested case‑control study[110] with 4429 cases of autism
spectrum disorder (1828 with and 2601 without intellectual
disability) and 43,277 age and sex matched controls in the
full sample (1679 cases of autism spectrum disorder and
16,845 controls with data on maternal anti‑depressant use
nested within a cohort (n = 589,114) of young people aged
0–17 years. Similar results are obtained in a recent rodent
study.[111]
Monoamine oxidase inhibitors
A study[112] on 21 prenatal exposures to monoamine oxidase
inhibitors (MAOIs) found a relative risk of 3.4 for congenital
malformations. In contrast, a case report[113] of phenelzine
use throughout pregnancy described a healthy outcome
for the patient and her infant. In some of more recent
studies,[66,76] MAOI have been studied in conjunction with
other SSRIs and SNRIs. One such retrospective case‑control
study[76] did not report adverse fetal outcomes with MAOI
use. However, in another population‑based prospective
cohort study, MAOI along with other SSRIs have been
found to be associated with increased risk of PPHN for
early exposure in pregnancy (relative risks [RR] =2.30),
for later exposure (RR = 2.56) and for both early and later
exposure (RR = 3.44) Nevertheless, MAOIs are best avoided
in pregnant women because of the risk of hypertensive
crisis.
Newer antidepressants
Some efforts were made in 2006[114] to review this issue. The
data is presented below.
Venlafaxine
Only two studies have evaluated the use of venlafaxine in
pregnancy. In one study,[57] venlafaxine was used in 150
women, and incidence of major malformations was similar
to the expected rate of 1–3%. In the second study,[115] 10
subjects who received venlafaxine during pregnancy
gave birth to healthy babies. A large prospective cohort
study[74] that included venlafaxine and other non‑SSRI
antidepressants found that the prevalence of cardiac
malformations was well below the prevalence rate at 0.6%
Indian J Psychiatry 57 (Supplement 2), July 2015
in the antidepressants as a group. Data obtained from the
Swedish Medical Birth Registry[116] also do not suggest an
increased risk of congenital malformations after exposure
to SNRI/NRIs. The limitations in terms of small sample
confounded interpretations.
Mirtazapine
A small case series[117] (n = 7) of mirtazapine use in
pregnancy found no perinatal complications or congenital
malformations in the infants. In another prospective
comparative study,[118] aiming to explore the teratogenic
potential of mirtazapine found that it was not associated
with a risk for major malformations.
Nefazodone, trazodone, and vilazodone
Einarson et al.[119] evaluated the effect of prenatal exposure
to nefazodone and trazodone, and found no significant
difference in the number of major congenital malformation.
No data on vilazodone could be found.[39]
Bupropion
In a study,[120] 136 women exposed to bupropion during the
first trimester of pregnancy were taken and there were 105
live births with no major malformations, however, this study
was plagued with a small sample size. Recent data have been
surfacing for bupropion safety. The Bupropion pregnancy
register final report[121] by GlaxoSmithKilne reported 3.6%
and 1.3% of infants exposed to bupropion were reported to
have congenital abnormalities and congenital heart defects,
respectively, from 1997 to 2008. A retrospective case‑control
study[122] that examined the risk of bupropion exposure
1‑month prior to conception until 3 months after conception
found that exposed infants were more likely to have left
outflow tract heart defects, but not other defects (odds
ratio [OR] =2.6; 95% CI: 1.2–5.7). Another case‑control
study[123] did not find an increased risk of congenital
malformations when they compared first‑trimester
bupropion exposure to first‑trimester exposure to other
antidepressants; and to bupropion exposure outside the first
trimester. A recent review[39] points out that even with the
possible increased of congenital heart defects the absolute
risk of a congenital heart defect remains low at 2.1/1000
births in exposed infants when compared to the estimated
prevalence of 0.82/1000 births in the general population.[52]
Guidelines to clinical decision making for antidepressant
use in pregnancy
General principles in reducing the risk of an adverse outcome
in pregnancy exposed to any psychotropic would include
adequate planning for pregnancy. One should consider
the pregnancy as “high‑risk pregnancy,” consider informed
consent, use the lowest effective dose for the shortest
period of time necessary, while focusing on psychotropic
medications, clinicians should not ignore other risk factors
for poor perinatal outcome, such as obesity, smoking, and
the use of alcohol or other substances of abuse and healthy
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
behavior, including adherence to a prenatal vitamin regimen
and to a schedule of prenatal care visits and maintenance of
a healthy diet must be supported.[8]
Management of depression during pregnancy depends on
the severity of the disorder. Mild depressive symptoms
during pregnancy may improve with nonpharmacological
treatments (interpersonal therapy). Pharmacological
intervention is warranted in pregnant women with severe
depression, including diminished oral intake, incapacitating
vegetative symptoms, suicidality, and presence of psychotic
symptoms.[22] Poor response to psychotherapy and patients
who cannot devote time to psychotherapy sessions due
to overwhelming demands of work, child‑care, single
parenthood, and financial strain also form candidates for
pharmacotherapy.[124]
For women who are stable and from the past history appear
to remain well for at least several months without taking
the medications discontinuation of an antidepressant prior
to conception might be thought of. Another reasonable
approach is to continue antidepressants until conception is
confirmed as by that time developing embryo will receive
minimal medication exposure since the uteroplacental
circulation does not form until 10–12 days postconception.[125]
For new‑onset depression in pregnancy, an SSRI is
generally accepted as the first line due to the fact that
they are well‑characterized and even though risks are
reported the volume of data is reassuring, and further
absolute risks interpreted are minimal.[39] However, if a
patient has had a positive response to any specific agent
from any class of antidepressants that agent should be
strongly considered.[124] Women may be more likely to have
a response to serotonergic agents, such as the SSRIs and
venlafaxine, than to nonserotonergic TCAs. Slow increases
in the dose are helpful in managing side effects. Dosages of
certain drugs (i.e. TCAs, lithium) may need to be increased
in the third trimester.
If possible, the MAOIs should be avoided for reasons cited in
the text. Data are too limited to provide a recommendation
for some newer antidepressants, but literature is emerging
for caution especially for paroxetine and bupropion use.
Short‑term discontinuation of an antidepressant may
produce withdrawal symptoms[124] is associated with a 75%
risk of relapse during pregnancy.[119,126] Therapy should be
tailor made to the patient taking into account the number
and severity of previous episodes and the time to relapse
after previous attempts at medication discontinuation.
For women with histories of rapid and severe relapses
after medication discontinuation, antidepressants need
to be maintained throughout the pregnancy. Overall,
in order to provide optimal clinical care to women and
their developing child, it is imperative to consider risks of
S360 Indian J Psychiatry 57 (Supplement 2), July 2015
treatment in the context of illness severity, consequences
of no treatment, under‑treatment, and individual
treatment preferences.[39]
Anxiolytics and hypnotics in pregnancy
The literature on the pharmacological treatment of anxiety
disorders occurring in pregnancy is very limited; what
is available focuses on treatments of panic disorder and
obsessive‑compulsive disorder (OCD). Pharmacological
agents such as SSRI (fluoxetine), TCA (imipramine), and
MAOI (phenelzine) and benzodiazepine agonists (alprazolam,
lorazepam, clonazepam, and diazepam) are the mainstay
in the management of panic disorders, whereas primary
anti‑obsessional agents include clomipramine, fluoxetine,
fluvoxamine, and sertraline.[8]
The effects due to the use of primary antidepressants as
anxiolytics have already been covered in the section on
antidepressant use during pregnancy. Since larger doses of
TCAs are generally required in the management of OCD, the
likelihood of withdrawal syndrome is increased. A withdrawal
syndrome has been reported with clomipramine.[127‑129]
A growing controversy is the possibility of perinatal
syndromes related to SSRI use during the third trimester
of pregnancy. In Summer 2004, the FDA opted to instruct
the makers of the SSRI and SNRI antidepressants to place
warnings on the package inserts describing the possible
occurrence of neurobehavioral symptoms in neonates
exposed to these medications late in the third trimester
and through labor and delivery. The subcommittee[130] also
recommended changes to the dosage and administration
section of the drug label advising physicians to consider
taper and discontinuation of these agents prior to labor
and delivery. Recent studies[55,131] have challenged this
notion pointing that there is no evidence suggesting this
approach reduces the incidence of PNAS or improves infant
outcomes. It also carries the risk of precipitating relapse or
postpartum depression and anxiety, particularly in high‑risk
individuals.
Benzodiazepine agonists in pregnancy
All major classes of benzodiazepine compounds diffuse
readily across the placenta to the fetus.[114]
Neonatal effects
The major neonatal side effects of benzodiazepines
include sedation and dependence with withdrawal signs.
A benzodiazepine‑induced “floppy infant syndrome”
characterized by muscular hypotonia, low Apgar
scores, hypothermia, impaired response to cold, and
neurologic depression can occur at the time of delivery in
benzodiazepine‑dependent neonates, even with the lower
doses used to treat anxiety disorders. Withdrawal signs
include hypertonia, hyper‑reflexia, restlessness, irritability,
seizures, abnormal sleep patterns, inconsolable crying,
tremors or jerking of the extremities, bradycardia, cyanosis,
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
chewing movements, and abdominal distention. These signs
can appear shortly after delivery to 3 weeks after birth and last
up to several months depending on the degree of dependence
and the pharmacokinetic profile of the benzodiazepine.[114]
Teratogenic effects
The data regarding the teratogenic potential of
benzodiazepines when pooled suggests adequate
reproductive safety.[114]
Neurobehavioral toxicity
Animal studies[132‑135] have suggested its occurrence with
some of the benzodiazepines. In humans, the findings
were mixed, no motor or cognitive deficits were observed
in children at 8 months of age, and no effects on IQ were
observed at 4 years of age.[136] Conversely, delayed motor
development and mental retardation were reported
in 7 of 8 children with in utero exposure to various
benzodiazepines.[137]
Salient issues relevant to individual agents are as follows
Diazepam
Diazepam has a long‑acting metabolite, dimethyldiazepam,
whose mean elimination half‑life is 73 (30–100) hours in
adults. The evidence that diazepam causes congenital
malformations, especially cleft lip/palate is controversial,[138]
however, association with floppy infant syndrome and PNAS
has been reported.[66,139]
Clonazepam
Clonazepam has the longest mean elimination half‑life of
23 (18–50) hours in adults. A limited surveillance study[140]
revealed three major birth defects (0.8 expected) in
19 pregnant women exposed to clonazepam. Other effects
attributed to this molecule include congenital heart disease,
ventral septal defect, hip dislocation, uteropelvic junction
obstruction, bilateral inguinal hernia, undescended testicle,
paralytic ileus of the small bowel, cyanosis, lethargy,
hypotonia, and apnea.[141] But in most cases, clonazepam
was used along with other antiepileptics like phenytoin
and barbiturates. In a large study[142] of 10,698 infants with
congenital anomalies, maternal use of clonazepam during
pregnancy was not significantly represented. Targeted
sonography for anomaly screening is recommended at
18–20 weeks of gestation.[114]
Lorazepam
Exposure to lorazepam has been linked to anal atresia and
neonatal withdrawal symptoms, such as low Apgar scores,
depressed respiration, hypothermia, poor suckling,
and jaundice. The neonatal withdrawal symptoms
can be severe because of shorter half‑life. Hence,
whenever possible lorazepam should be avoided during
pregnancy.[141]
Indian J Psychiatry 57 (Supplement 2), July 2015
Alprazolam
Use of alprazolam in pregnancy does not increase the risk of
major malformations. It has been linked with malformations
like cleft lip, inguinal hernia, hypospadias, cryptorchidism,
tracheoesophageal fistula, patent ductus arteriosus,
microcephaly, strabismus, congenital hip dislocation, fused
lacrimal duct, Down’s syndrome, cat’s eye with Pierre
Robin syndrome, pyloric stenosis, umbilical hernia, ankle
inversion, lipomeningocele, neonatal withdrawal syndrome.
Whenever possible, its use should be avoided in the first
trimester.[141]
Guidelines for clinical decision making in the use of anxiolytics
and hypnotics during pregnancy
Exposure to any type of benzodiazepine during the first
3 months of pregnancy should be avoided. However, its
use during pregnancy is not absolutely contraindicated.
For many anxiety disorders, nonpharmacological treatment
are the first line, however, when medications are indicated
physicians should use the benzodiazepines that have long
safety records and should prescribe a benzodiazepine as
monotherapy at the lowest effective dosage for the shortest
possible duration. Furthermore, high peak concentrations
of the drugs should be avoided by dividing the daily
dosage into at least two doses. Finally, the best means of
monitoring the safety and efficacy of therapy should be
determined.[141]
From the viewpoint of the fetus, SSRI is recommended for
preventive therapy for panic disorder during pregnancy.
When a benzodiazepine is indicated for the treatment of an
acute panic disorder in the pregnant patient, shorter half‑life
agents such as oxazepam, temazepam, lormetazepam are
preferred during pregnancy to longer‑acting diazepam and
clonazepam. According to some lorazepam is preferred
over alprazolam for preventive therapy, because it has
a somewhat longer duration of action, it lacks active
metabolites, and it does not seem to be associated with
an immediate and as severe a withdrawal syndrome in the
neonate.[8]
An SSRI is recommended first line for the treatment of OCD
during pregnancy with adequate risk‑benefit assessment.[56]
Indian contribution
Clinical evidence from India in the estimation of risk
following exposure to psychotropic drugs in general and
antidepressants or anxiolytics and hypnotics, in particular,
is very scarce. Probably, it is due to the nonmaintenance
of pregnancy register in the country that the adverse drug
exposures fail to be reported.
Sethi and Manchanda[143] analyzed all the neonates with one
or more congenital abnormality during the 15‑month period
at the Queens Mary Hospital, KGMC Lucknow. Retrospective
inquiry into the antenatal period of the mothers was
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
conducted to gain information for the psychotropic
drug history during pregnancy. Of 3825 births during
15 months, congenital abnormalities were observed in 58
neonates (incidence, 1.5%). 41 (70.7%) had a single defect
and 17 (29.3%) had more than one defect. Of the drugs
reportedly used during pregnancy, history of diazepam
and chlorpromazine was available in one patient each
during the second and third trimester only. History of other
drugs in first trimester included hormonal preparations
(5), analgesics (3), antiemetics (2), benzathine penicillin
(1), ergot (1), Ayurvedic and Homeopathic compounds
(1 each).
Other studies[144‑146] done even earlier reported regarding
the incidence of congenital malformations with varied
molecules not limited to psychotropics. Some studies
reported an incidence of 2–4%, while others of 1.4%.
This area has been relatively little explored thereafter.
The reasons could be many ranging from ethical concerns
regarding the designs of the study to poor recording and
reporting of adverse outcomes due to lack of pregnancy
register. The gap in the knowledge is huge, especially when
the work done across the globe has improvised significantly
both in terms of awareness of the psychiatric comorbidities
in pregnancy and design of the prospective longitudinal
studies which are methodologically sound to answer the
clinical conundrums associated with decision making in this
high‑risk population.
SECTION 2
Issues related to psychotropic use during lactation
Maternal and neonatal pharmacokinetics
According to Buist et  al.,[147] psychotropic drug exposure
during lactation involves three distinct processes: The
pharmacokinetics of the mother, transport of the drug into
breast milk, and the pharmacokinetics of the developing
infant.
Maternal factors include ionization fraction, protein binding
of the drugs, dosage, frequency of drug administration, and
the absorption of the dose by the mother. Blood flow to the
breast, breast metabolism of the drug and milk composition
also exert an influence.[147]
Neonatal absorption is influenced by pH of the breast milk;
distribution is affected by differing fat/muscle/extracellular
and total body water ratios. As well, neonates have less
plasma protein and lipolysis occurring shortly after birth
that brings about an increase in free fatty acids which
compete with the drugs for protein binding.[147]
Neonates have a reduced capacity to metabolize and
excrete drugs and drug metabolites can accumulate in the
infant’s system and though only a very small amount of drug
S362 Indian J Psychiatry 57 (Supplement 2), July 2015
may cross from mother to infant at any one feed, over time
this may lead to potentially toxic levels. Hepatic metabolic
processes of oxidation and glucuronidation are usually
impaired in neonates. Finally, the process of breastfeeding
itself can influence how much drug enters the infant’s
system. Suckling, time on each breast, amount consumed
per feed, feeding intervals, and the interval between drug
consumption and feeding all need to be considered.[130]
Antidepressants exposure during lactation
There is extensive literature focusing on antidepressants
exposure in nursing mothers. The available database in this
respect is provided in Table 2.
Guidelines for antidepressant use in lactation
The data tabulated above have been synthesized by
many comprehensive reviews and practice guidelines by
some scientific organizations[203‑211] which provide some
recommendations in clinical decision making.
Basic recommendation of risk‑benefit analysis is always
upheld and the pointers for consideration include risk of
untreated maternal illness for the mother and the infant,
the risk/benefit of the specific treatment for the mother
and the infant, the risk/benefit of being breastfed or not
for the infant, the possible maternal risks of renouncing
breastfeeding, and the mother’s desire to breastfeed.
Nonpharmacological interventions such as psychotherapy
should be considered, particularly for mild to moderate
depression but for moderate to severe depression and in
some cases also with an anxiety disorder, pharmacotherapy
is indicated. Moreover, for women with previous
postpartum depression or women who have been treated
with antidepressants during pregnancy, antidepressants are
the preferred mode of treatment in the prophylaxis or new
episodes/relapses.
It is usually recommended that paroxetine and sertraline
should be preferred over other SSRIs due to the low infant
exposure for these drugs. When possible, fluoxetine and
citalopram should be avoided or used with caution due to
the higher infant plasma levels than for other drugs and the
possible risk of adverse effects in the infant.[204‑206] However, in
case of prior effective treatment with fluoxetine or citalopram,
or if the mother has used one of these drugs during pregnancy,
it could also be used in the postpartum period.[204,205] Berle
and Spigset[211] suggest that when antidepressant treatment
is indicated in the postpartum period, the women should
generally not be advised to discontinue breastfeeding.
Scarce data exist for drugs such as fluvoxamine, venlafaxine,
duloxetine, reboxetine, bupropion, and mirtazapine and
should not be considered as first‑line therapies, but they
can be used in special cases.[204,205,209]
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Table 2: Maternal dose, infant plasma concentrations of antidepressants after breast milk excretion and observed
Study (reference)
TCA
Amitriptyline
Erickson et al.[148]
Bader and Newman[149]
Brixen‑Rasmussen
et al.[150]
Pittard and O’Neal[151]
Imipramine
Sovner and Orsulak[152]
Desipramine
Stancer and Reed[153]
Doxepin
Kemp et al.[154]
Matheson et al.[155]
Frey et al., 1999[156]
Dothiepin
Rees et al.[157]
Amoxapine
Gelenberg, 1979[158]
Clomipramine
Schimmel et al., 1991[34]
Trazodone
Verbeeck et al.,[159]
SSRI
Sertraline
Altshuler et al.,1995[160]
Mammen et al., 1997[161]
Stowe et al., 1997[162]
Wisner et al., 1998[163]
Kristensen et al., 1998[164]
Birnbaum et al., 1999[165]
Dodd et al., 2001[166]
Epperson et al., 2001[167]
Hendrick et al., 2001[168]
Stowe et al., 2003[169]
Fluoxetine
Burch and Wells 1992[170]
Lester et al., 1993[171]
Taddio et al., 1996[172]
Yoshida et al., 1998[173]
 Ram and Gandotra: Psychotropics in pregnancy and lactation
effects on infants
Sample size Maternal dose Infant‑serum concentration Comments
1 150 mg/d ND Concentration in fetal blood was equal to that
in maternal plasma
1 100 mg/d 50 µg/kg Concentration in fetal blood was in excess to
that in maternal plasma
1 75 10 µg/kg N/A
1 100 ND No adverse effect reported
1 200 20 µg/kg Concentration in excess in fetal blood
1 300 70 µg/kg No adverse effect reported
1 150 50 µg/kg N/A
1 75 20 µg/kg N/A
1 75 Low but therapeutic levels metabolite Poor suck, swallow, hypotonia, vomiting
of desmethyldoxepin reported
2 75 2 µg/kg No adverse effect noted
1 N/A 0.07% of maternal dose N/A
n=3 75-150 mg >10% of maternal plasma dose Caution to be used
6 50 1% of maternal dose N/A
n=1 100 mg Sertraline: ND No adverse effects reported; mother was also
Desmethylsertraline: ND taking nortriptyline
n=3 50-100 mg Sertraline: <2.0 ng/mL Benign neonatal sleep myoclonus reported in
Desmethylsertraline: <2.0 ng/mL one infant, resolved by 6 months
n=11 25-150 mg Sertraline: ND to 3 ng/mL No adverse effects reported; very low infant
Desmethylsertraline: ND to 10 ng/mL blood levels
n=9 50-200 mg Sertraline: ND to 3 ng/mL No adverse effects were reported
Desmethylsertraline: ND to 6 ng/mL
1 and 2 infants had unusually high
sertraline and desmethyl sertraline
levels, respectively
n=8 1.05 mg/kg/day Sertraline: ND MWAD: ~0.2-1.32%; no adverse effects
Desmethylsertraline: ND reported
n=3 50-100 mg Sertraline: <5 ng/mL No adverse effects reported
Desmethylsertraline: <5 ng/mL
n=10 50-150 mg Sertraline levels were below No adverse effects reported
the detection limit of 2 ng/mL in all
infants
n=14 25-200 mg Sertraline: ND Infants experienced little to no blockade of
Desmethylsertraline: ND platelet serotonin reuptake
n=30 25-200 mg Sertraline: <1-8 ng/mL No adverse effects reported
Desmethylsertraline: <12 ng/mL
n=26 25-200 mg Sertraline: ND to 3 ng/mL MWAD: ~5.4%, during lactation
Desmethylsertraline: ND to 10 ng/mL
n=1 20 mg N/A No adverse effects reported
n=1 20 mg Fluoxetine: 340 ng/mL High infant drug levels correlated with
symptoms
n=10 0.39 mg/kg/day Infant daily dose estimated to be MWAD: 10.8%; no adverse effects reported
0.65 mg
n=4 20-40 mg Fluoxetine: ND MWAD: 3-10%; no adverse effects reported
Norfluoxetine: ND
Contd...
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Table 2: Maternal dose, infant plasma concentrations of antidepressants after breast milk excretion and observed
Study (reference)
Brent and Wisner
1998[174]
Birnbaum et al., 1999[165]
Chambers et al., 1999[175]
Kristensen et al., 1999[176]
Hendrick et al., 2001[168]
Suri et al., 2002[177]
Epperson et al., 2003[178]
Paroxetine
Spigset et al., 1996[179]
Begg et al., 1999[180]
Ohman et al., 1999[181]
Misri et al., 2000[182]
Birnbaum et al., 1999[165]
Hendrick et al., 2000[183]
Stowe et al., 2000[184]
Merlob et al., 1992[185]
Citalopram
Jensen et al., 1997[186]
Spigset et al., 1997[187]
Schmidt et al., 2000[188]
Rampono et al., 2000[189]
Heikkinen et al., 2002[190]
Lee et al., 2004[191]
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
effects on infants
Sample size Maternal dose Infant‑serum concentration Comments
n=1 20 mg Fluoxetine: 61 ng/mL Transient seizure‑like activity and one
Norfluoxetine: 57 ng/mL episode peripheral cyanosis reported
by mother (all unwitnessed by medical
personnel); mother was also taking
carbamazepine and buspirone
n=13 20-80 mg Fluoxetine: ND‑82 ng/mL No adverse effects reported; detectable
concentrations of fluoxetine and/or
norfluoxetine were noted in 78% of exposed
infants; all but three infants were exposed
in utero as well as during lactation; one
infant also exposed to a TCA, another to
clonazepam, and another to clonazepam and
valproic acid
n=26 20-40 mg N/A Evidence of reduced growth curves in
fluoxetine‑exposed infants; no behavioral
effects reported; retrospective cohort study
design
n=14 0.51 mg/kg/day Fluoxetine: 20-252 ng/L MWAD: average was 6.81% (range 2.15-
Norfluoxetine: 17-187 ng/L 12%); colic was reported in two infants
n=19 10-60 mg Fluoxetine: <1-84 ng/mL No adverse effects reported; infants of
Norfluoxetine: <1-265 ng/mL mothers taking<20 mg/day likely to have
very low blood levels
n=10 Mean dose Fluoxetine: ND‑84 ng/mL Using several methods of calculation of
34±12.8 mg Norfluoxetine: ND‑39 ng/mL infant exposure, maximum infant dose over
an entire year of nursing would appear to
equal approximately 120 mg
n=11 N/A N/A Measured platelet serotonin levels before and
during maternal treatment with fluoxetine.
No effects seen in 10 of the 11 infants
n=1 20 mg N/A No adverse effects reported
n=10 10-30 mg ND MWAD: 1.3%; no adverse effects reported
n=6 20-40 mg N/A MWAD: 0.7-2.9%; no adverse effects
reported
n=24 10-40 mg <2.0 ng/mL MWAD: 1.1%; no adverse effects reported
n=2 30 mg <20 ng/mL No adverse effects reported; one infant
exposed in utero and during lactation, the
other exclusively during lactation but also
exposed to clonazepam in utero and during
lactation
n=16 5-30 mg ND No adverse effects reported
n=16 Average=23.1 <2.0 ng/mL No adverse effects reported
mg
n=27 20 mg N/A Irritability reported in one infant; prospective
cohort study design
n=1 20 mg Citalopram: 7 nM MWAD: ~5%, during lactation; no adverse
Desmethylcitalopram: <10 nM effects reported
n=3 20-40 mg N/A MWAD: 0.7-5.9% during lactation;
single‑dose citalopram; no adverse effects
reported
n=1 40 mg Citalopram: 12.7 ng/mL MWAD: 5.4% during lactation; sleep
disturbance in infant, improved with decrease
to 20 mg daily
n=7 20-40 mg Citalopram: <2.3 mg/mL MWAD: 4.4-5.1% during lactation
Desmethylcitalopram: <2.2 mg/mL
n=11 20-40 mg Citalopram: ~3.3 mg/mL MWAD: 0.2-0.3% during lactation
Desmethylcitalopram: ~2.8 mg/mL at
2 months old
n=31 10-60 mg N/A Prospective cohort study; one report of
decreased sleep and restlessness in infant
after citalopram use initiated
Contd...
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 Ram and Gandotra: Psychotropics in pregnancy and lactation

Table 2: Maternal dose, infant plasma concentrations of antidepressants after breast milk excretion and observed
effects on infants
Study (reference) Sample size Maternal dose Infant‑serum concentration Comments
Fluvoxamine
Wright et al., 1991[192] n=1 200 mg N/A No adverse effects reported
Yoshida et al., 1997[193] n=1 100 mg N/A No adverse effects reported
Hendrick et al., 2001[168] n=50 100-150 mg ND No adverse effects reported
Piontek et al., 2001[194] n=2 50-300 mg ND No adverse effects reported up to 3 years
after exposure
Kristensen et al., 2002[195] n=2 50-150 mg N/A MWAD: 0.8-1.38%; no adverse effects
reported
Bupropion
Briggs et al., 1993[196] n=1 300 mg ND No adverse effects reported
Baab et al., 2002[197] n=2 75 mg/bid Below limit of detection No adverse effects reported
150 mg/d
Chaudron and n=1 150 mg (SR) Drug blood level not obtained 6 months infant had seizure after exposure
Schoenecker 2004[198] Infant was not febrile during seizure to two doses. Infant evaluated in pediatric
which was witnessed by the mother. seizure clinic, laboratory test and
The description of the behavior was electroencephalogram unremarkable
consistent with seizures of a 6 months
infant
Venlafaxine
Hendrick et al., 2001[199] n=2 75 mg, 150 mg Limit of detection was Metabolite is measurable in infants. No
10 ng/mL. Parent drug not detectable. adverse effects were reported
Metabolite O‑desmethyl venlafaxine
was 16 ng/mL in one infant and
12 ng/mL in the other
Ilett et al., 2002[200] n=6 225-300 mg 5 mg/L in one infant MWAD: 5.5-7.3%; no adverse effects
ND in five other infants reported
Hendrick et al., 2003[201] n=78 infants Difference in body weight compared to
whose mothers normative population was assessed, and no
were treated difference was found
with SSRI
(n=75) and on
venlafaxine (n=3)
Newport et al., 2009[202] n=13 The theoretical infant venlafaxine/ No adverse events were observed in the
desvenlafaxine dose was nursing infants
0.208 mg/kg/d, and the relative infant
venlafaxine/desvenlafaxine dose was
8.1%. The theoretical and relative
infant doses for desvenlafaxine were
197% and 224% higher, respectively,
than those for venlafaxine
Source: Modified from Epperson CN, Ballew J. Postpartum depression: A common complication of childbirth. In: Hendrick V, Editor. Psychiatric Disorders in Pregnancy
and Postpartum: Principles and Treatment. Totowa, New Jersey: Humana Press; 2006. p. 41‑83. ND – Nondetectable; MWAD – Maternal weight‑adjusted dose;
N/A – Not applicable; TCA – Tricyclic antidepressant; SSRI – Selective serotonin reuptake inhibitor

Some of the reviews and guidelines recommend infant
monitoring, particularly if the infant is sick, premature or
has a low body weight.[204,205,209]
Routine breast milk and/or infant serum sampling
for drug concentration analysis are generally not
recommended.[204,205,207] It can, however, be helpful if the
infant has signs that may be indicative of drug exposure.[208]
Pumping and discarding breast milk to reduce the
exposure has been suggested to be of little value. It is
important to reinforce the importance of breastfeeding
and its benefits but not at all costs; we need to present a
balanced view.
Limitations of the studies estimating drug concentrations
in infant
There is no definitive consensus as to the best means to
monitor the nursing infant’s antidepressant exposure in the
clinical setting. Monitoring infant serum concentrations is
poorly reliable due to the fact that the laboratory assays
do not have the sensitivity required to detect the typical
serum concentrations of breastfeeding infants, further,
in the absence of meaningful clinical correlation, even a
detectable infant serum concentration is uninterpretable.[19]
Mathematical models to forecast risk exposure via lactation
are available but are derived from the collection of a single
random breast milk sample and ignore pharmacokinetics of
medications in the fetus.[19]

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 Ram and Gandotra: Psychotropics in pregnancy and lactation
Gentile[206] recently proposed a specific safety index
for antidepressant use in breastfeeding mothers. The
index is expressed as the ratio between the reported
number of infants with adverse events after exposure to
an antidepressant through milk and the reported total
number of exposed infants for the same antidepressant,
multiplied by 100. It is suggested that a value <2
indicates that the drug is relatively safe; a value of 2.1–10
indicates that the drug should be used with great caution,
and a value above 10 indicates that the drug should be
contraindicated in breastfeeding mothers. The index has
some bottlenecks in terms of low reliability with less
sample size, less reliable interpretations depending on
the quality of raw data.[203,204]
Benzodiazepine anxiolytics during lactation
Benzodiazepines are commonly used medications in
postpartum psychiatric disorders. Well‑controlled studies
in this respect are lacking, and much of the evidence is
based on case reports.
In one such report,[212] oxazepam was identified in the
urine of an 8‑day‑old breastfed infant whose mother had
received diazepam 30 mg/day for 3 days. The child became
lethargic, lost weight, and showed electroencephalogram
changes consistent with a sedative drug. In another
study,[213] oxazepam has been measured in the breast milk
of a 33‑year‑old patient who received 30 mg/day of the
drug for 3 days. Samples of oxazepam determination were
collected each morning and evening and then 10 and 34 h
after the final dose. In both plasma and milk, the half‑life
was 12 h, and the milk plasma ratio was between 0.1 and
0.3 throughout the sampling period. It was calculated that
a suckling baby would be exposed to <1/1000th of the
maternal dose. Other studies[213‑215] show excretion data as
low as 1% with oxazepam and up to 8% with alprazolam.
Erkkola and Kanto[216] estimated diazepam and its major
metabolite, N‑desmethyldiazepam, in the milk and the
infants’ plasma of three women who received 30 mg/day of
diazepam for 6 days after parturition. While there was an
increase in the concentration of parent drug and metabolite
from day 4 to 6 in the mothers’ milk and plasma, the
concentration in the infants’ plasma declined which was
attributed to the maturation of the infants’ drug metabolizing
capacity. A similar type of study was conducted by Brandt[217]
and the metabolite levels (N‑desmethyldiazepam) always
exceeded those of the parent drug which was explained
by the difference in the protein binding between two
compounds.
Studies[218‑220] have also shown the passage of lorazepam,
lormetazepam, and quazepam into breast milk.
Whitelaw et al.[221] examined the effects of lorazepam on the
children born to 51 women treated for up to 5 days after
S366 Indian J Psychiatry 57 (Supplement 2), July 2015
delivery with either an oral (n = 35) or an intravenous (n = 16)
preparation. Plasma, cord blood, and urine samples were
measured in 26 deliveries and breast milk samples in one
patient. Neonatal excretion of lorazepam was gradual.
Elimination in preterm babies was much slower than in
full‑term children. According to these authors, the low
concentrations of drug involved were not associated with
obvious adverse effects except for sedation lasting about 48 h.
The hypnotics such as nitrazepam and flunitrazepam have
also been observed to be distributed into milk.[222,223]
Two small studies[224,225] have suggested that the
nonbenzodiazepine hypnotics zolpidem and zaleplon are
safe in nursing.
Guidelines for benzodiazepine use in lactation
In general, short‑term, low‑dose use of benzodiazepines
is considered fairly safe during lactation. No long‑term
adverse effects have been reported in exclusively breastfed
children whose mothers were taking benzodiazepines on a
regular basis,[165] but there have been a few case reports[226]
of transient sedation in breastfed infants, which improved
on cessation of breastfeeding. In cases where high doses
are to be used or repeated administration will be needed
then breastfeeding should probably be discontinued. The
shorter‑acting benzodiazepines (alprazolam, lorazepam)
are favored over those with longer half‑lives (clonazepam,
diazepam). Moreover, the minimum dosage required for
symptom relief should be used, and the infant should be
monitored regularly. Single doses of benzodiazepines do
not require any limitation on breastfeeding.
Work done in India
The literature in this field is again sparse, and the
authors did not come across any study that attempted to
address this issue. The literature worldwide is deficient
in many ways to guide clinical decision making in cases
with psychotropic use in lactation. It appears that the
enlightened community in India will have to consider
these research limitations and undertake steps to push for
building research evidence base to make the best possible
clinical judgment in these cases. The work at global level
is considering elucidating the neurodevelopmental and
genetic models to unearth the least exposure pathways
to the fetus during lactation[227] and in this respect, our
country seems to be at a very nascent stage where even
the basic pregnancy register or even crude fetal drug
estimation studies are not in place.
CONCLUSIONS
A pregnant patient with comorbid mental illness would
require a careful evaluation of the risk‑benefit assessment
of psychotropic drug exposure leading to maternal benefit
versus fetal harm and vice versa. The available evidence both
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 Ram and Gandotra: Psychotropics in pregnancy and lactation
during pregnancy and lactation does not report gross harm
due to drug exposure in pooled data and provides some
cautions concerning safety of use of some molecules. The
available evidence needs to be viewed with an element of
caution in the absence of well‑designed controlled studies.
Further, it is unlikely that such kind of studies would be
forthcoming due to legal and ethical considerations.
Similarly, during lactation, psychotropic drug not detected
in the fetus does not completely abort the risk to the
neonate and an approach of least possible drug exposure to
the fetus should be followed. The guidelines that have been
presented following an extensive review of the literature
would help to guide clinical decision making both during
pregnancy and lactation to minimize risk to the mother as
well as the fetus. The research evidence in this aspect in
India is miniscule, and a proper plan needs to be in place
starting from the establishment of pregnancy registers to
designing of studies to build an evidence base.
Future directions
Future efforts at the global level include attempts to
delineate the neurobiological and neurodevelopmental and
pharmacogenetic avenues in exploring psychotropic drug
exposure in the treated mother and information on this issue
can allow further re‑evaluation of risk‑benefit assessment in
this respect.[19,227] Attempts are also being made at the level of
regulatory agencies to improvise existing drug labeling and
information policies. Pregnancy labels of the future likely will
address areas such as clinical considerations, summary risk
assessment, and data to support the assessment. The goals of
the initiative are to highlight clinical considerations relevant
to making prescribing decisions for a particular medication
for pregnant women, including disease risk and the risk of
no treatment. This label also will include information that
may assist clinicians when counseling women whose fetuses
are inadvertently exposed to medications in early gestation.
The summary risk assessment section may be a narrative
text that articulates, as best can be determined, the risk of
exposure based on animal and human data.[15]
Effective perinatal services in India need to start from the scratch.
The attempt to gain insight into the research evidence regarding
psychotropic drug exposure in pregnancy and lactation might
start with a scientific and political will to establish pregnancy
registers. Issues related to the ethical conduct of pregnancy
registry research, including informed consent, and the timing
and circumstances of outcome reporting are clearly complex,
but this initiative would mark a welcome beginning in gathering
clinical evidence. Further awareness and cooperation among
the clinical experts including pediatricians, gynecologists, and
physicians would be required for the better care of this high‑risk
population. The researchers in India need to develop a potential
insight into developmental pharmacology and biology that can
be gained through the careful study of adverse effects of drug
exposure to the fetus.
Indian J Psychiatry 57 (Supplement 2), July 2015
REFERENCES
1. Janicak PG, Davis JM, Preskorn SH, Ayd FJ. Principles and Practice of
Psychopharmacotherapy. 3rd  ed. Philadelphia: Lippincott, William and
Wilkins; 2001.
2. Miller  LJ. Clinical strategies for the use of psychotropic drugs during
pregnancy. Psychiatr Med 1991;9:275‑98.
3. Miller LJ. Pharmacotherapy during the perinatal period. The Hatherleigh
Guide to Psychopharmacology. New York: Hatherleigh Press; 1999.
4. Wintz CJ. Difficult decisions: Women of childbearing age, mental illness,
and psychopharmacologic therapy. J  Am Psychiatr Nurses Assoc
1999;5:5‑14.
5. Stowe  ZN, Strader  J, James  R, Nemeroff  CB. Psychopharmacology
during pregnancy and lactation. In: Schatzberg AF, Nemeroff CB, editors.
Textbook of Psychopharmacology. 2nd  ed. Washington, DC: American
Psychiatric Press, Inc; 1998.
6. Gjere  NA. Psychopharmacology in pregnancy. J  Perinat Neonatal Nurs
2001;14:12‑25.
7. Wisner  KL, Perel  JM, Wheeler  SB. Tricyclic dose requirements across
pregnancy. Am J Psychiatry 1993;150:1541‑2.
8. Use of psychoactive medication during pregnancy and possible effects
on the fetus and newborn. Committee on Drugs. American Academy of
Pediatrics. Pediatrics 2000;105 (4 Pt 1):880‑7.
9. Ward  RM. Pharmacology of the maternal‑placental‑fetal‑unit and fetal
therapy. Prog Pediatr Cardiol 1996;5:79‑89.
10. Kerns  LL. Treatment of mental disorders in pregnancy. A  review of
psychotropic drug risks and benefits. J Nerv Ment Dis 1986;174:652‑9.
11. Shader  RI, Greenblatt  DJ. More on drugs and pregnancy. J  Clin
Psychopharmacol 1995;15:1‑2.
12. Pastuszak  A, Schick‑Boschetto  B, Zuber  C, Feldkamp  M, Pinelli  M,
Sihn S, et al. Pregnancy outcome following first‑trimester exposure to
fluoxetine (Prozac). JAMA 1993;269:2246‑8.
13. Meltolan  MW. Take two aspirin tablets or not? Risk of medication use
during pregnancy. Mother Baby J 1999;4:25‑32.
14. Sachdeva P, Patel BG, Patel BK. Drug use in pregnancy; a point to ponder!
Indian J Pharm Sci 2009;71:1‑7.
15. Nonacs  R, Cohen  LS. Assessment and treatment of depression during
pregnancy: An update. Psychiatr Clin North Am 2003;26:547‑62.
16. Centers for Disease Control and Prevention  (CDC). Update on overall
prevalence of major birth defects – Atlanta, Georgia, 1978‑2005. MMWR
Morb Mortal Wkly Rep 2008;57:1‑5.
17. Langman J. Human development‑normal and abnormals. In: Langman J,
editor. Medical Embryology. Baltimore: Williams and Wilkins; 1985. p. 123.
18. Moore  K, Persaud  T. The Developing Human: Clinically Oriented
Embryology. Philadelphia: W.B. Saunders; 1993.
19. Newport  DJ, Wilcox  MM, Stowe  ZN. Antidepressants during pregnancy
and lactation: Defining exposure and treatment issues. Semin Perinatol
2001;25:177‑90.
20. Pacifici  GM, Nottoli  R. Placental transfer of drugs administered to the
mother. Clin Pharmacokinet 1995;28:235‑69.
21. Altshuler  LL, Hendrick  VC. Pregnancy and psychotropic medication:
Changes in blood levels. J Clin Psychopharmacol 1996;16:78‑80.
22. Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J. Pharmacologic
management of psychiatric illness during pregnancy: Dilemmas and
guidelines. Am J Psychiatry 1996;153:592‑606.
23. Sjoqvist F, Bergfors PG, Borga O, Lind M, Ygge H. Plasma disappearance
of nortriptyline in a newborn infant following placental transfer from an
intoxicated mother: Evidence for drug metabolism. Br J Clin Pharmacol
1972;80:496‑500.
24. Heikkine  T, Ekblad  U, Laine  K. Transplacental transfer of citalopram,
fluoxetine and their primary demethylated metabolites in isolated perfused
human placenta. BJOG 2002;109:1003‑8.
25. Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D. Placental
passage of antidepressant medications. Am J Psychiatry 2003;160:993‑6.
26. Loughhead  AM, Stowe  ZN, Newport  DJ, Ritchie  JC, DeVane  CL,
Owens MJ. Placental passage of tricyclic antidepressants. Biol Psychiatry
2006;59:287‑90.
27. Giudici V, Pogliani L, Cattaneo D, Dilillo D, Zuccotti GV. Serotonin reuptake
inhibitors in pregnancy: Can genes help us in predicting neonatal adverse
outcome? Biomed Res Int 2014;2014:276918.
28. Cohen  L, Altshuler  L. Pharmacologic management of psychiatric illness
during pregnancy and the postpartum period. In: Rosenbaum  J, editor.
Psychiatric Clinics of North America: Annual of Drug Therapy. Philadelphia:
WB Saunders; 1997. p. 21‑60.
29. Loebstein  R, Koren  G. Pregnancy outcome and neurodevelopment
of children exposed in utero to psychoactive drugs: The Motherisk
experience. J Psychiatry Neurosci 1997;22:192‑6.
30. McElhatton PR, Garbis HM, Eléfant E, Vial T, Bellemin B, Mastroiacovo P,
et al. The outcome of pregnancy in 689 women exposed to therapeutic
S367
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
 Ram and Gandotra: Psychotropics in pregnancy and lactation
doses of antidepressants. A collaborative study of the European Network of
Teratology Information Services (ENTIS). Reprod Toxicol 1996;10:285‑94.
31. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation: A preliminary
report. Int J Psychiatry Med 1991;21:157‑71.
32. Cowe L, Lloyd DJ, Dawling S. Neonatal convulsions caused by withdrawal
from maternal clomipramine. Br Med J (Clin Res Ed) 1982;284:1837‑8.
33. Eggermont E. Withdrawal symptoms in neonates associated with maternal
imipramine therapy. Lancet 1973;2:680.
34. Schimmell MS, Katz EZ, Shaag Y, Pastuszak A, Koren G. Toxic neonatal
effects following maternal clomipramine therapy. J Toxicol Clin Toxicol
1991;29:479-84.
35. Webster PA. Withdrawal symptoms in neonates associated with maternal
antidepressant therapy. Lancet 1973;2:318‑9.
36. Bromiker  R, Kaplan  M. Apparent intrauterine fetal withdrawal from
clomipramine hydrochloride. JAMA 1994;272:1722‑3.
37. Ter Horst  PG, Jansman  FG, van Lingen  RA, Smit  JP,
de  Jong‑van  den  Berg  LT, Brouwers  JR. Pharmacological aspects of
neonatal antidepressant withdrawal. Obstet Gynecol Surv 2008;63:267‑79.
38. Kieviet  N, Dolman  KM, Honig  A. The use of psychotropic medication
during pregnancy: How about the newborn? Neuropsychiatr Dis Treat
2013;9:1257‑66.
39. Byatt N, Deligiannidis KM, Freeman MP. Antidepressant use in pregnancy:
A critical review focused on risks and controversies. Acta Psychiatr Scand
2013;127:94‑114.
40. Falterman CG, Richardson CJ. Small left colon syndrome associated with
maternal ingestion of psychotropic drugs. J Pediatr 1980;97:308‑10.
41. Shearer WT, Schreiner RL, Marshall RE. Urinary retention in a neonate
secondary to maternal ingestion of nortriptyline. J Pediatr 1972;81:570‑2.
42. Ali SF, Buelke‑Sam J, Newport GD, Slikker W Jr. Early neurobehavioral
and neurochemical alterations in rats prenatally exposed to imipramine.
Neurotoxicology 1986;7:365‑80.
43. Vorhees CV, Brunner RL, Butcher RE. Psychotropic drugs as behavioral
teratogens. Science 1979;205:1220‑5.
44. Vernadakis  A, Parker  KK. Drugs and the developing central nervous
system. Pharmacol Ther 1980;11:593‑647.
45. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, et al.
Neurodevelopment of children exposed in utero to antidepressant drugs.
N Engl J Med 1997;336:258‑62.
46. Nulman  I, Rovet  J, Stewart  DE, Wolpin  J, Pace‑Asciak  P, Shuhaiber  S,
et al. Child development following exposure to tricyclic antidepressants
or fluoxetine throughout fetal life: A prospective, controlled study. Am J
Psychiatry 2002;159:1889‑95.
47. Simon  GE, Cunningham  ML, Davis  RL. Outcomes of prenatal
antidepressant exposure. Am J Psychiatry 2002;159:2055‑61.
48. Addis  A, Koren  G. Safety of fluoxetine during the first trimester of
pregnancy: A meta‑analytical review of epidemiological studies. Psychol
Med 2000;30:89‑94.
49. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes
in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010‑5.
50. Cohen LS, Heller VL, Bailey JW, Grush L, Ablon JS, Bouffard SM. Birth
outcomes following prenatal exposure to fluoxetine. Biol Psychiatry
2000;48:996‑1000.
51. Goldstein DJ. Effects of third trimester fluoxetine exposure on the newborn.
J Clin Psychopharmacol 1995;15:417‑20.
52. Reller  MD, Strickland  MJ, Riehle‑Colarusso  T, Mahle  WT, Correa  A.
Prevalence of congenital heart defects in metropolitan Atlanta, 1998‑2005.
J Pediatr 2008;153:807‑13.
53. Källén B, Nilsson E, Olausson PO. Antidepressant use during pregnancy:
Comparison of data obtained from a prescription register and from
antenatal care records. Eur J Clin Pharmacol 2011;67:839‑45.
54. Källén BA, Otterblad Olausson  P. Maternal use of selective serotonin
re‑uptake inhibitors in early pregnancy and infant congenital malformations.
Birth Defects Res A Clin Mol Teratol 2007;79:301‑8.
55. Warburton W, Hertzman C, Oberlander TF. A register study of the impact
of stopping third trimester selective serotonin reuptake inhibitor exposure
on neonatal health. Acta Psychiatr Scand 2010;121:471‑9.
56. Kulin  NA, Pastuszak  A, Sage  SR, Schick‑Boschetto  B, Spivey  G,
Feldkamp  M, et al. Pregnancy outcome following maternal use of the
new selective serotonin reuptake inhibitors: A prospective controlled
multicenter study. JAMA 1998;279:609‑10.
57. Einarson  A, Fatoye  B, Sarkar  M, Lavigne  SV, Brochu  J, Chambers  C,
et al. Pregnancy outcome following gestational exposure to
venlafaxine: A multicenter prospective controlled study. Am J Psychiatry
2001;158:1728‑30.
58. Cohen LS, Rosenbaum JF. Fluoxetine in pregnancy [letter]. N Engl J Med
1997;336:872.
59. Robert  E. Treatment depression in pregnancy. N  Engl J Med
1996;335:1056‑8.
60. Ericson  A, Källén B, Wiholm  B. Delivery outcome after the use of
antidepressants in early pregnancy. Eur J Clin Pharmacol 1999;55:503‑8.
S368 Indian J Psychiatry 57 (Supplement 2), July 2015
61. Inman W, Kobotu K, Pearce G, Wilton L. Prescription event monitoring of
paroxetine. PEM Reports 1993;1206:1-44.
62. Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM, National
Birth Defects Prevention Study. Use of selective serotonin‑reuptake
inhibitors in pregnancy and the risk of birth defects. N  Engl J Med
2007;356:2684‑92.
63. Louik C, Lin AE, Werler MM, Hernández‑Díaz S, Mitchell AA. First‑trimester
use of selective serotonin‑reuptake inhibitors and the risk of birth defects.
N Engl J Med 2007;356:2675‑83.
64. Wogelius P, Nørgaard M, Gislum M, Pedersen L, Munk E, Mortensen PB,
et al. Maternal use of selective serotonin reuptake inhibitors and risk of
congenital malformations. Epidemiology 2006;17:701‑4.
65. Bakker MK, De Walle HE, Wilffert B, de Jong‑Van den Berg LT. Fluoxetine
and infantile hypertrophic pylorus stenosis: A signal from a birth
defects‑drug exposure surveillance study. Pharmacoepidemiol Drug Saf
2010;19:808‑13.
66. Reis M, Källén B. Delivery outcome after maternal use of antidepressant
drugs in pregnancy: An update using Swedish data. Psychol Med
2010;40:1723‑33.
67. Diav‑Citrin  O, Shechtman  S, Weinbaum  D, Wajnberg  R, Avgil  M,
Di Gianantonio  E, et al. Paroxetine and fluoxetine in pregnancy: A
prospective, multicentre, controlled, observational study. Br J Clin
Pharmacol 2008;66:695‑705.
68. Malm H, Artama M, Gissler M, Ritvanen A. Selective serotonin reuptake
inhibitors and risk for major congenital anomalies. Obstet Gynecol
2011;118:111‑20.
69. Oberlander TF, Warburton W, Misri S, Riggs W, Aghajanian J, Hertzman C.
Major congenital malformations following prenatal exposure to serotonin
reuptake inhibitors and benzodiazepines using population‑based health
data. Birth Defects Res B Dev Reprod Toxicol 2008;83:68‑76.
70. Kornum JB, Nielsen RB, Pedersen L, Mortensen PB, Nørgaard M. Use of
selective serotonin‑reuptake inhibitors during early pregnancy and risk of
congenital malformations: Updated analysis. Clin Epidemiol 2010;2:29‑36.
71. Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH. Selective
serotonin reuptake inhibitors in pregnancy and congenital malformations:
Population based cohort study. BMJ 2009;339:b3569.
72. Bérard A, Ramos E, Rey E, Blais L, St‑André M, Oraichi D. First trimester
exposure to paroxetine and risk of cardiac malformations in infants:
The importance of dosage. Birth Defects Res B Dev Reprod Toxicol
2007;80:18‑27.
73. Wen SW, Yang Q, Garner P, Fraser W, Olatunbosun O, Nimrod C, et al.
Selective serotonin reuptake inhibitors and adverse pregnancy outcomes.
Am J Obstet Gynecol 2006;194:961‑6.
74. Einarson A, Choi J, Einarson TR, Koren G. Incidence of major malformations
in infants following antidepressant exposure in pregnancy: Results of a
large prospective cohort study. Can J Psychiatry 2009;54:242‑6.
75. Einarson A, Choi J, Koren G, Einarson T. Outcomes of infants exposed
to multiple antidepressants during pregnancy: Results of a cohort study.
J Popul Ther Clin Pharmacol 2011;18:e390‑6.
76. Ramos  E, St‑André M, Rey  E, Oraichi  D, Bérard A. Duration of
antidepressant use during pregnancy and risk of major congenital
malformations. Br J Psychiatry 2008;192:344‑50.
77. Wisner KL, Sit DK, Hanusa BH, Moses‑Kolko EL, Bogen DL, Hunker DF,
et al. Major depression and antidepressant treatment: Impact on
pregnancy and neonatal outcomes. Am J Psychiatry 2009;166:557‑66.
78. Klieger‑Grossmann  C, Weitzner  B, Panchaud  A, Pistelli  A, Einarson  T,
Koren  G, et al. Pregnancy outcomes following use of escitalopram: A
prospective comparative cohort study. J Clin Pharmacol 2012;52:766‑70.
79. Williams M, Wooltorton E. Paroxetine (Paxil) and congenital malformations.
CMAJ 2005;173:1320‑1.
80. Cole  JA, Ephross  SA, Cosmatos  IS, Walker  AM. Paroxetine in
the first trimester and the prevalence of congenital malformations.
Pharmacoepidemiol Drug Saf 2007;16:1075‑85.
81. Wurst  KE, Poole  C, Ephross  SA, Olshan AF. First trimester paroxetine
use and the prevalence of congenital, specifically cardiac, defects:
A meta‑analysis of epidemiological studies. Birth Defects Res A Clin Mol
Teratol 2010;88:159‑70.
82. Bar‑Oz  B, Einarson  T, Einarson  A, Boskovic  R, O’Brien  L, Malm  H,
et al. Paroxetine and congenital malformations: Meta‑analysis and
consideration of potential confounding factors. Clin Ther 2007;29:918‑26.
83. Gentile S, Bellantuono C. Selective serotonin reuptake inhibitor exposure
during early pregnancy and the risk of fetal major malformations: Focus on
paroxetine. J Clin Psychiatry 2009;70:414‑22.
84. Einarson TR, Einarson A. Newer antidepressants in pregnancy and rates
of major malformations: A meta‑analysis of prospective comparative
studies. Pharmacoepidemiol Drug Saf 2005;14:823‑7.
85. O’Brien L, Einarson TR, Sarkar M, Einarson A, Koren G. Does paroxetine
cause cardiac malformations? J Obstet Gynaecol Can 2008;30:696‑701.
86. Rahimi R, Nikfar S, Abdollahi M. Pregnancy outcomes following exposure
to serotonin reuptake inhibitors: A meta‑analysis of clinical trials. Reprod
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
 Ram and Gandotra: Psychotropics in pregnancy and lactation
Toxicol 2006;22:571‑5.
87. Spencer  MJ. Fluoxetine hydrochloride  (Prozac) toxicity in a neonate.
Pediatrics 1993;92:721‑2.
88. Kwon P, Lefkowitz W. Poor neonatal adaptation in term infant. Fluoxetine
toxicity. Pediatr Ann 2008;37:131‑3.
89. Mhanna MJ, Bennet JB 2nd, Izatt SD. Potential fluoxetine chloride (Prozac)
toxicity in a newborn. Pediatrics 1997;100:158‑9.
90. Mohan CG, Moore JJ. Fluoxetine toxicity in a preterm infant. J Perinatol
2000;20:445‑6.
91. Stiskal JA, Kulin N, Koren G, Ho T, Ito S. Neonatal paroxetine withdrawal
syndrome. Arch Dis Child Fetal Neonatal Ed 2001;84:F134‑5.
92. Costei AM, Kozer  E, Ho T, Ito  S, Koren  G. Perinatal outcome following
third trimester exposure to paroxetine. Arch Pediatr Adolesc Med
2002;156:1129‑32.
93. Dahl  ML, Olhager  E, Ahlner  J. Paroxetine withdrawal syndrome in a
neonate. Br J Psychiatry 1997;171:391‑2.
94. Nordeng H, Lindemann R, Perminov KV, Reikvam A. Neonatal withdrawal
syndrome after in utero exposure to selective serotonin reuptake inhibitors.
Acta Paediatr 2001;90:288‑91.
95. Boucher N, Bairam A, Beaulac‑Baillargeon L. A new look at the neonate’s
clinical presentation after in utero exposure to antidepressants in late
pregnancy. J Clin Psychopharmacol 2008;28:334‑9.
96. Herbst  F, Gortner  L. Paroxetine withdrawal syndrome as differential
diagnosis of acute neonatal encephalopathy? Z Geburtshilfe Neonatol
2003;207:232‑4.
97. Galbally M, Lewis AJ, Lum J, Buist A. Serotonin discontinuation syndrome
following in utero exposure to antidepressant medication: Prospective
controlled study. Aust N Z J Psychiatry 2009;43:846‑54.
98. Suri  R, Altshuler  L, Hendrick  V, Rasgon  N, Lee  E, Mintz  J. The impact
of depression and fluoxetine treatment on obstetrical outcome. Arch
Womens Ment Health 2004;7:193‑200.
99. Maschi  S, Clavenna  A, Campi  R, Schiavetti  B, Bernat  M, Bonati  M.
Neonatal outcome following pregnancy exposure to antidepressants: A
prospective controlled cohort study. BJOG 2008;115:283‑9.
100. Consortium on Safe Labor, Hibbard  JU, Wilkins  I, Sun  L, Gregory  K,
Haberman  S, et al. Respiratory morbidity in late preterm births. JAMA
2010;304:419‑25.
101. Administration. UFAD. FDA Medwatch Drug Alert on
Effexor  (venlafaxine HCL) and Effecor XR  (venlafaxine HCL);
2004. Available from: http://www.fda.gov/Safety/MedWatch/
SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154975.
htm.[Last cited on 2011 Dec 22].
102. Chambers CD, Hernandez‑Diaz S, Van Marter LJ, Werler MM, Louik C,
Jones  KL, et al. Selective serotonin‑reuptake inhibitors and risk of
persistent pulmonary hypertension of the newborn. N  Engl J Med
2006;354:579‑87.
103. Källén B, Olausson  PO. Maternal use of selective serotonin re‑uptake
inhibitors and persistent pulmonary hypertension of the newborn.
Pharmacoepidemiol Drug Saf 2008;17:801‑6.
104. Heritage  CK, Cunningham  MD. Association of elective repeat cesarean
delivery and persistent pulmonary hypertension of the newborn. Am J
Obstet Gynecol 1985;152:627‑9.
105. Hernández‑Díaz S, Van Marter LJ, Werler MM, Louik C, Mitchell AA. Risk
factors for persistent pulmonary hypertension of the newborn. Pediatrics
2007;120:e272‑82.
106. Kieler  H, Artama  M, Engeland A, Ericsson  O, Furu  K, Gissler  M, et al.
Selective serotonin reuptake inhibitors during pregnancy and risk of
persistent pulmonary hypertension in the newborn: Population based
cohort study from the five Nordic countries. BMJ 2012;344:d8012.
107. Administration USFAD. FDA Drug Safety Communication: Selective
serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy
and reports of a rare heart and lung condition in newborn babies. 2011.
Available from: http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm.
[Last accessed on 2015 Mar 07]. [12/4/11 ed].
108. Hallberg P, Sjöblom V. The use of selective serotonin reuptake inhibitors
during pregnancy and breast‑feeding: A review and clinical aspects. J Clin
Psychopharmacol 2005;25:59‑73.
109. Weikum WM, Oberlander TF, Hensch TK, Werker JF. Prenatal exposure
to antidepressants and depressed maternal mood alter trajectory of infant
speech perception. Proc Natl Acad Sci U S A 2012;109 Suppl 2:17221‑7.
110. Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C. Parental
depression, maternal antidepressant use during pregnancy, and risk of
autism spectrum disorders: Population based case‑control study. BMJ
2013;346:f2059.
111. Simpson KL, Weaver KJ, de Villers‑Sidani E, Lu JY, Cai Z, Pang Y, et al.
Perinatal antidepressant exposure alters cortical network function in
rodents. Proc Natl Acad Sci U S A 2011;108:18465‑70.
112. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy.
Littleton, Mass: Publishing Science Group; 1977.
113. Gracious  BL, Wisner  KL. Phenelzine use throughout pregnancy and
Indian J Psychiatry 57 (Supplement 2), July 2015
the puerperium: Case report, review of the literature, and management
recommendations. Depress Anxiety 1997;6:124‑8.
114. Grover S, Avasthi A, Sharma Y. Psychotropics in pregnancy: Weighing the
risks. Indian J Med Res 2006;123:497‑512.
115. Yaris F, Kadioglu M, Kesim M, Ulku C, Yaris E, Kalyoncu NI, et al. Newer
antidepressants in pregnancy: Prospective outcome of a case series.
Reprod Toxicol 2004;19:235‑8.
116. Lennestål R, Källén B. Delivery outcome in relation to maternal use of
some recently introduced antidepressants. J  Clin Psychopharmacol
2007;27:607‑13.
117. Saks BR. Mirtazapine: Treatment of depression, anxiety, and hyperemesis
gravidarum in the pregnant patient: A report of 7  cases. Arch Womens
Ment Health 2001;4:165‑70.
118. Djulus J, Koren G, Einarson TR, Wilton L, Shakir S, Diav‑Citrin O, et al.
Exposure to mirtazapine during pregnancy: A prospective, comparative
study of birth outcomes. J Clin Psychiatry 2006;67:1280‑4.
119. Einarson A, Bonari  L, Voyer‑Lavigne  S, Addis A, Matsui  D, Johnson  Y,
et al. A multicentre prospective controlled study to determine the safety
of trazodone and nefazodone use during pregnancy. Can J Psychiatry
2003;48:106‑10.
120. Chun‑Fai‑Chan  B, Koren  G, Fayez  I, Kalra  S, Voyer‑Lavigne  S,
Boshier  A, et al. Pregnancy outcome of women exposed to bupropion
during pregnancy: A prospective comparative study. Am J Obstet Gynecol
2005;192:932‑6.
121. Glaxosmithkline. The Bupropion Pregnancy Registry Final Report; 2008.
Available from: http://www.pregnancyregistry.gsk.com/documents/bup_
report_final_2008.pdf. [Last accessed on 2015 Mar 07].
122. Alwan S, Reefhuis J, Botto LD, Rasmussen SA, Correa A, Friedman JM,
et al. Maternal use of bupropion and risk for congenital heart defects. Am
J Obstet Gynecol 2010;203:52.e1‑6.
123. Cole  JA, Modell  JG, Haight  BR, Cosmatos  IS, Stoler  JM, Walker  AM.
Bupropion in pregnancy and the prevalence of congenital malformations.
Pharmacoepidemiol Drug Saf 2007;16:474‑84.
124. Berga  SL, Parry  BL, Moses‑Kolko  EL. Psychiatry and reproductive
medicine. In: Saddock  BJ, Saddock  VA, Ruiz  P, editors. Kaplan and
Sadocks’s Comprehensive Text Book of Psychiatry. 9th  ed., Vol. II.
New York: Lippinkot William and Wilkins; 2009. p. 2539‑62.
125. Creasy RK, Resnik R. Maternal‑Fetal Medicine: Principles and Practice.
3rd ed. Philadelphia: WB Saunders; 1994. p. 96‑7.
126. Rosenbaum  JF, Fava  M, Hoog  SL, Ascroft  RC, Krebs  WB. Selective
serotonin reuptake inhibitor discontinuation syndrome: A randomized
clinical trial. Biol Psychiatry 1998;44:77‑87.
127. Cohen LS, Nonacs RM, Bailey JW, Viguera AC, Reminick AM, Altshuler LL,
et al. Relapse of depression during pregnancy following antidepressant
discontinuation: A preliminary prospective study. Arch Womens Ment
Health 2004;7:217‑21.
128. Singh  S, Gulati  S, Narang  A, Bhakoo  ON. Non‑narcotic withdrawal
syndrome in a neonate due to maternal clomipramine therapy. J Paediatr
Child Health 1990;26:110.
129. Schimmell MS, Katz EZ, Shaag Y, Pastuszak A, Koren G. Toxic neonatal
effects following maternal clomipramine therapy. J  Toxicol Clin Toxicol
1991;29:479‑84.
130. Epperson CN, Ballew J. Postpartum depression: A common complication
of childbirth. In: Hendrick  V, editor. Psychiatric Disorders in Pregnancy
and Postpartum: Principles and Treatment. Totowa, New Jersey: Humana
Press; 2006. p. 41‑83.
131. Moses‑Kolko  EL, Bogen  D, Perel  J, Bregar  A, Uhl  K, Levin  B, et al.
Neonatal signs after late in utero exposure to serotonin reuptake
inhibitors: Literature review and implications for clinical applications. JAMA
2005;293:2372‑83.
132. Brioni JD, Orsingher OA. Operant behavior and reactivity to the anticonflict
effect of diazepam in perinatally undernourished rats. Physiol Behav
1988;44:193‑8.
133. Kellogg  CK. Benzodiazepines: Influence on the developing brain. Prog
Brain Res 1988;73:207‑28.
134. Deutch AY, Gruen RJ, Roth RH. The effects of perinatal diazepam exposure
on stress‑induced activation of the mesotelencephalic dopamine system.
Neuropsychopharmacology 1989;2:105‑14.
135. De Salvia  MA, Cagiano  R, Lacomba  C, Cuomo  V. Neurobehavioral
changes produced by developmental exposure to benzodiazepines. Dev
Pharmacol Ther 1990;15:173‑7.
136. Hartz SC, Heinonen OP, Shapiro S, Siskind V, Slone D. Antenatal exposure
to meprobamate and chlordiazepoxide in relation to malformations, mental
development, and childhood mortality. N Engl J Med 1975;292:726‑8.
137. Laegreid L. Clinical observations in children after prenatal benzodiazepine
exposure. Dev Pharmacol Ther 1990;15:186‑8.
138. Briggs  GG, Freeman  RK, Yaffe  SJ, editors. Drugs in Pregnancy and
Lactation: A Reference Guide to Fetal and Neonatal Risk. 4th ed. Baltimore,
MD: Williams and Wilkins; 1994.
139. Uzun S, Kozumplik O, Jakovljevic M, Sedic B. Side effects of treatment
S369
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
 Ram and Gandotra: Psychotropics in pregnancy and lactation
with benzodiazepines. Psychiatr Danub 2010;22:90‑3.
140. Rosa  FW, Baum  C. Computerized on‑line pharmaceutical surveillance
system (COMPASS) teratology. Reprod Toxicol 1993;7:639‑40.
141. Iqbal MM, Sobhan T, Ryals T. Effects of commonly used benzodiazepines
on the fetus, the neonate, and the nursing infant. Psychiatr Serv
2002;53:39‑49.
142. Czeizel AE, Bod M, Halász P. Evaluation of anticonvulsant drugs during
pregnancy in a population‑based Hungarian study. Eur J Epidemiol
1992;8:122‑7.
143. Sethi  N, Manchana  M. Maternal drug histories and congenital
abnormalities. Indian J Psychiatry 1978;20:191‑2.
144. Ghosh S, Bali L. Congenital malformations in the newborn. Indian J Child
Health 1963;12:448‑52.
145. Saifullah S, Chandra RK, Pathak IC, Dhall GI. Congenital malformations
in new born. A prospective longitudinal study. A preliminary report on 1000
consecutive births. Indian Pediatr 1967;4:251‑61.
146. Sharma  B, Bajpai  PC, Sharma  NL. Some observations on congenital
malformations. Indian J Pediatr 1972;39:286‑92.
147. Buist  A, Norman  TR, Dennerstein  L. Breastfeeding and the use of
psychotropic medication: A review. J Affect Disord 1990;19:197‑206.
148. Erickson SH, Smith GH, Heidrich F. Tricyclics and breast feeding. Am J
Psychiatry 1979;136:1483‑4.
149. Bader TF, Newman K. Amitriptyline in human breast milk and the nursing
infant’s serum. Am J Psychiatry 1980;137:855‑6.
150. Brixen‑Rasmussen  L, Halgrener  J, Jørgensen A. Amitriptyline and
nortriptyline excretion in human breast milk. Psychopharmacology (Berl)
1982;76:94‑5.
151. Pittard WB 3rd, O’Neal W Jr. Amitriptyline excretion in human milk. J Clin
Psychopharmacol 1986;6:383‑4.
152. Sovner R, Orsulak PJ. Excretion of imipramine and desipramine in human
breast milk. Am J Psychiatry 1979;136:451‑2.
153. Stancer  HC, Reed  KL. Desipramine and 2‑hydroxydesipramine in
human breast milk and the nursing infant’s serum. Am J Psychiatry
1986;143:1597‑600.
154. Kemp  J, Ilett  KF, Booth  J, Hackett  LP. Excretion of doxepin and
N‑desmethyldoxepin in human milk. Br J Clin Pharmacol 1985;20:497‑9.
155. Matheson  I, Pande  H, Alertsen  AR. Respiratory depression caused by
N‑desmethyldoxepin in breast milk. Lancet 1985;2:1124.
156. Frey  OR, Scheidt  P, von Brenndorff  AI. Adverse effects in a newborn
infant breast‑fed by a mother treated with doxepin. Ann Pharmacother
1999;33:690‑3.
157. Rees JA, Glass RC, Spome GA. Serum and breast milk concentrations of
dothiepin. Practitioner 1976;217:686.
158. Gelenberg  AJ. Single case study. Amoxapine, a new antidepressant,
appears in human milk. J Nerv Ment Dis 1979;167:635‑6.
159. Verbeeck RK, Ross SG, McKenna EA. Excretion of trazodone in breast
milk. Br J Clin Pharmacol 1986;22:367‑70.
160. Altshuler  LL, Burt  VK, McMullen  M, Hendrick  V. Breastfeeding and
sertraline: A 24‑hour analysis. J Clin Psychiatry 1995;56:243‑5.
161. Mammen  OK, Perel  JM, Rudolph  G, Foglia  JP, Wheeler  SB. Sertraline
and norsertraline levels in three breastfed infants. J  Clin Psychiatry
1997;58:100‑3.
162. Stowe  ZN, Owens  MJ, Landry  JC, Kilts  CD, Ely  T, Llewellyn  A, et al.
Sertraline and desmethylsertraline in human breast milk and nursing
infants. Am J Psychiatry 1997;154:1255‑60.
163. Wisner KL, Perel JM, Blumer J. Serum sertraline and N‑desmethylsertraline
levels in breast‑feeding mother‑infant pairs. Am J Psychiatry
1998;155:690‑2.
164. Kristensen JH, Ilett KF, Dusci LJ, Hackett LP, Yapp P, Wojnar‑Horton RE,
et al. Distribution and excretion of sertraline and N‑desmethylsertraline in
human milk. Br J Clin Pharmacol 1998;45:453‑7.
165. Birnbaum CS, Cohen LS, Bailey JW, Grush LR, Robertson LM, Stowe ZN.
Serum concentrations of antidepressants and benzodiazepines in nursing
infants: A case series. Pediatrics 1999;104:e11.
166. Dodd S, Stocky A, Buist A, Burrows GD, Norman TR. Sertraline analysis
in the plasma of breast‑fed infants. Aust N Z J Psychiatry 2001;35:545‑6.
167. Epperson N, Czarkowski KA, Ward‑O’Brien D, Weiss E, Gueorguieva R,
Jatlow  P, et al. Maternal sertraline treatment and serotonin transport in
breast‑feeding mother‑infant pairs. Am J Psychiatry 2001;158:1631‑7.
168. Hendrick  V, Fukuchi  A, Altshuler  L, Widawski  M, Wertheimer  A,
Brunhuber MV. Use of sertraline, paroxetine and fluvoxamine by nursing
women. Br J Psychiatry 2001;179:163‑6.
169. Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC, Sternberg K, Cohen LS,
et al. The pharmacokinetics of sertraline excretion into human breast
milk: Determinants of infant serum concentrations. J  Clin Psychiatry
2003;64:73‑80.
170. Burch  KJ, Wells  BG. Fluoxetine/norfluoxetine concentrations in human
milk. Pediatrics 1992;89 (4 Pt 1):676‑7.
171. Lester BM, Cucca J, Andreozzi L, Flanagan P, Oh W. Possible association
between fluoxetine hydrochloride and colic in an infant. J Am Acad Child
S370 Indian J Psychiatry 57 (Supplement 2), July 2015
Adolesc Psychiatry 1993;32:1253‑5.
172. Taddio  A, Ito  S, Koren  G. Excretion of fluoxetine and its metabolite,
norfluoxetine, in human breast milk. J Clin Pharmacol 1996;36:42‑7.
173. Yoshida  K, Smith  B, Craggs  M, Kumar  RC. Fluoxetine in breast‑milk
and developmental outcome of breast‑fed infants. Br J Psychiatry
1998;172:175‑8.
174. Brent NB, Wisner KL. Fluoxetine and carbamazepine concentrations in a
nursing mother/infant pair. Clin Pediatr (Phila) 1998;37:41‑4.
175. Chambers CD, Anderson PO, Thomas RG, Dick LM, Felix RJ, Johnson KA,
et al. Weight gain in infants breastfed by mothers who take fluoxetine.
Pediatrics 1999;104:e61.
176. Kristensen JH, Ilett KF, Hackett LP, Yapp P, Paech M, Begg EJ. Distribution
and excretion of fluoxetine and norfluoxetine in human milk. Br J Clin
Pharmacol 1999;48:521‑7.
177. Suri  R, Stowe  ZN, Hendrick  V, Hostetter  A, Widawski  M, Altshuler  LL.
Estimates of nursing infant daily dose of fluoxetine through breast milk.
Biol Psychiatry 2002;52:446‑51.
178. Epperson CN, Jatlow PI, Czarkowski K, Anderson GM. Maternal fluoxetine
treatment in the postpartum period: Effects on platelet serotonin and
plasma drug levels in breastfeeding mother‑infant pairs. Pediatrics
2003;112:e425.
179. Spigset  O, Carleborg  L, Norström A, Sandlund  M. Paroxetine level in
breast milk. J Clin Psychiatry 1996;57:39.
180. Begg  EJ, Duffull  SB, Saunders  DA, Buttimore  RC, Ilett  KF, Hackett  LP,
et al. Paroxetine in human milk. Br J Clin Pharmacol 1999;48:142‑7.
181. Ohman R, Hägg S, Carleborg L, Spigset O. Excretion of paroxetine into
breast milk. J Clin Psychiatry 1999;60:519‑23.
182. Misri  S, Kim  J, Riggs  KW, Kostaras  X. Paroxetine levels in postpartum
depressed women, breast milk, and infant serum. J  Clin Psychiatry
2000;61:828‑32.
183. Hendrick  V, Stowe ZN, Altshuler LL, Hostetter A, Fukuchi A. Paroxetine
use during breast‑feeding. J Clin Psychopharmacol 2000;20:587‑9.
184. Stowe ZN, Cohen LS, Hostetter A, Ritchie JC, Owens MJ, Nemeroff CB.
Paroxetine in human breast milk and nursing infants. Am J Psychiatry
2000;157:185‑9.
185. Merlob  P, Mor  N, Litwin A. Transient hepatic dysfunction in an infant of
an epileptic mother treated with carbamazepine during pregnancy and
breastfeeding. Ann Pharmacother 1992;26:1563‑5.
186. Jensen  PN, Olesen  OV, Bertelsen  A, Linnet  K. Citalopram and
desmethylcitalopram concentrations in breast milk and in serum of mother
and infant. Ther Drug Monit 1997;19:236‑9.
187. Spigset O, Carieborg L, Ohman R, Norström A. Excretion of citalopram in
breast milk. Br J Clin Pharmacol 1997;44:295‑8.
188. Schmidt K, Olesen OV, Jensen PN. Citalopram and breast‑feeding: Serum
concentration and side effects in the infant. Biol Psychiatry 2000;47:164‑5.
189. Rampono  J, Kristensen  JH, Hackett  LP, Paech  M, Kohan  R, Ilett  KF.
Citalopram and demethylcitalopram in human milk; distribution, excretion
and effects in breast fed infants. Br J Clin Pharmacol 2000;50:263‑8.
190. Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K. Citalopram in pregnancy
and lactation. Clin Pharmacol Ther 2002;72:184‑91.
191. Lee  A, Woo  J, Ito  S. Frequency of infant adverse events that are
associated with citalopram use during breast‑feeding. Am J Obstet
Gynecol 2004;190:218‑21.
192. Wright S, Dawling S, Ashford JJ. Excretion of fluvoxamine in breast milk.
Br J Clin Pharmacol 1991;31:209.
193. Yoshida  K, Smith  B, Craggs  M, Kumar  RC. Investigation of
pharmacokinetics and of possible adverse effects in infants exposed to
tricyclic antidepressants in breast‑milk. J Affect Disord 1997;43:225‑37.
194. Piontek CM, Wisner KL, Perel JM, Peindl KS. Serum fluvoxamine levels in
breastfed infants. J Clin Psychiatry 2001;62:111‑3.
195. Kristensen  JH, Hackett  LP, Kohan  R, Paech  M, Ilett  KF. The amount of
fluvoxamine in milk is unlikely to be a cause of adverse effects in breastfed
infants. J Hum Lact 2002;18:139‑43.
196. Briggs  GG, Samson  JH, Ambrose  PJ, Schroeder  DH. Excretion of
bupropion in breast milk. Ann Pharmacother 1993;27:431‑3.
197. Baab SW, Peindl KS, Piontek CM, Wisner KL. Serum bupropion levels in
2 breastfeeding mother‑infant pairs. J Clin Psychiatry 2002;63:910‑1.
198. Chaudron LH, Schoenecker CJ. Bupropion and breastfeeding: A case of a
possible infant seizure. J Clin Psychiatry 2004;65:881‑2.
199. Hendrick  V, Altshuler  L, Wertheimer  A, Dunn  WA. Venlafaxine and
breast‑feeding. Am J Psychiatry 2001;158:2089‑90.
200. Ilett  KF, Kristensen  JH, Hackett  LP, Paech  M, Kohan  R, Rampono  J.
Distribution of venlafaxine and its O‑desmethyl metabolite in human milk
and their effects in breastfed infants. Br J Clin Pharmacol 2002;53:17‑22.
201. Hendrick  V, Smith  LM, Hwang  S, Altshuler  LL, Haynes  D. Weight gain
in breastfed infants of mothers taking antidepressant medications. J Clin
Psychiatry 2003;64:410‑2.
202. Newport  DJ, Ritchie  JC, Knight  BT, Glover  BA, Zach  EB, Stowe  ZN.
Venlafaxine in human breast milk and nursing infant plasma: Determination
of exposure. J Clin Psychiatry 2009;70:1304‑10.
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
 Ram and Gandotra: Psychotropics in pregnancy and lactation
203. Weissman AM, Levy BT, Hartz AJ, Bentler S, Donohue M, Ellingrod VL,
et al. Pooled analysis of antidepressant levels in lactating mothers, breast
milk, and nursing infants. Am J Psychiatry 2004;161:1066‑78.
204. Lanza di Scalea  T, Wisner  KL. Antidepressant medication use during
breastfeeding. Clin Obstet Gynecol 2009;52:483‑97.
205. Berle JØ, Spigset O. Maternal antidepressant use and breastfeeding. Curr
Med Lit Psychiatry 2008;19:33‑7.
206. Gentile S. Use of contemporary antidepressants during breastfeeding: A
proposal for a specific safety index. Drug Saf 2007;30:107‑21.
207. Ragan  K, Stowe  ZN, Newport  DJ. Use of antidepressants and mood
stabilizers in breast‑feeding women. In: Cohen LS, Nonacs RM, editors.
Mood and Anxiety Disorders During Pregnancy and Postpartum.(Review
of Psychiatry Series, Volume 24, Number 4; Oldham JM and Riba  MB,
series editors). Washington, DC: American Psychiatric Publishing; 2005.
p. 105‑44.
208. National Collaborating Centre for Mental Health. NICE Guideline on
Clinical Management and Service Guidance. Antenatal and Postnatal
Mental Health. No.  45; 2007. Available from: http://www.nice.org.uk/
nicemedia/pdf/CG45fullguideline.pdf. [Last accessed on 2010 Jan 31].
209. Academy of Breastfeeding Medicine Protocol Committee. ABM clinical
protocol #18: Use of antidepressants in nursing mothers. Breastfeed Med
2008;3:44‑52.
210. ACOG Committee on Practice Bulletins  –  Obstetrics. ACOG practice
bulletin: Clinical management guidelines for obstetrician‑gynecologists
number 92, April 2008 (replaces practice bulletin number 87, November
2007). Use of psychiatric medications during pregnancy and lactation.
Obstet Gynecol 2008;111:1001‑20.
211. Berle  JO, Spigset  O. Antidepressant use during breastfeeding. Curr
Womens Health Rev 2011;7:28‑34.
212. Patrick MJ, Tilstone WJ, Reavey P. Diazepam and breast‑feeding. Lancet
1972;1:542‑3.
213. Wretlind M. Excretion of oxazepam in breast milk. Eur J Clin Pharmacol
1987;33:209‑10.
214. Stebler  T, Guentert  TW. Determination of diazepam and nordazepam
in milk and plasma in the presence of oxazepam and temazepam.
J Chromatogr 1991;564:330‑7.
Indian J Psychiatry 57 (Supplement 2), July 2015
215. Oo CY, Kuhn RJ, Desai N, Wright CE, McNamara PJ. Pharmacokinetics
in lactating women: Prediction of alprazolam transfer into milk. Br J Clin
Pharmacol 1995;40:231‑6.
216. Erkkola R, Kanto J. Diazepam and breast‑feeding. Lancet 1972;1:1235‑6.
217. Brandt R. Passage of diazepam and desmethyldiazepam into breast milk.
Arzneimittelforschung 1976;26:454‑7.
218. Summerfield RJ, Nielsen MS. Excretion of lorazepam into breast milk. Br
J Anaesth 1985;57:1042‑3.
219. Hümpel M, Stoppelli  I, Milia  S, Rainer  E. Pharmacokinetics and
biotransformation of the new benzodiazepine, lormetazepam, in man. III.
Repeated administration and transfer to neonates via breast milk. Eur J
Clin Pharmacol 1982;21:421‑5.
220. Hilbert  JM, Gural  RP, Symchowicz  S, Zampaglione  N. Excretion of
quazepam into human breast milk. J Clin Pharmacol 1984;24:457‑62.
221. Whitelaw AG, Cummings AJ, McFadyen IR. Effect of maternal lorazepam
on the neonate. Br Med J (Clin Res Ed) 1981;282:1106‑8.
222. Reider  J, Wendt  G. Pharmacokinetics and metabolism of the hypnotic
nitrazepam. In: Garattini  S, Mussini  E, Randall  LO, editors. The
Benzodiazepines. New York, NY: Raven Press; 1973. p. 99‑127.
223. Kanto J, Aaltonen L, Kangas L, Erkkola R, Pitkanen Y. Placental transfer
and breast milk levels of flunitrazepam. Curr Ther Res 1979;26:539‑46.
224. Pons G, Francoual C, Guillet P, Moran C, Hermann P, Bianchetti G, et al.
Zolpidem excretion in breast milk. Eur J Clin Pharmacol 1989;37:245‑8.
225. Darwish M, Martin PT, Cevallos WH, Tse S, Wheeler S, Troy SM. Rapid
disappearance of zaleplon from breast milk after oral administration to
lactating women. J Clin Pharmacol 1999;39:670‑4.
226. Dusci  LJ, Good  SM, Hall  RW, Ilett  KF. Excretion of diazepam and its
metabolites in human milk during withdrawal from combination high dose
diazepam and oxazepam. Br J Clin Pharmacol 1990;29:123‑6.
227. Homberg  JR, Schubert  D, Gaspar  P. New perspectives on the
neurodevelopmental effects of SSRIs. Trends Pharmacol Sci 2010;31:60‑5.
Source of Support: Nil, Conflict of Interest: None declared
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REVIEW ARTICLE

Antipsychotics in pregnancy and lactation

Girish N. Babu, Geetha Desai1, Prabha S. Chandra1
SDM College of Medical Sciences and Hospital, Dharwad, 1Department of Psychiatry, NIMHANS, Bengaluru, Karnataka,
India

ABSTRACT

Research on psychotropic medications during pregnancy and lactation is limited as often involves complex ethical
issues. Information on safety of psychotropic drugs during these critical phases is either inconclusive or undetermined.
Many women with severe mental illness have unplanned pregnancies and require antipsychotic medication during
pregnancy and lactation. Multiple issues have to be considered while choosing safe treatments for pregnant and lactating
women and the best approach is to individualize the treatment. Medication should be guided primarily by its safety data
and by the psychiatric history of the patient. Important issues to be kept in mind include pre-pregnancy counseling for all
women, including planning pregnancies; folate supplementation, discussion with patient and family regarding options,
and active liaison with obstetricians, ultrasonologists and pediatricians. Whenever possible, non-pharmacological
approaches should be used in addition.

Key words: Antipsychotic, atypical antipsychotic, lactation, neonatal toxicity, neurotoxicity, pregnancy, teratogen

GENERAL PRINCIPLES
Research on psychotropic medications during pregnancy is
complicated by numerous factors, often involving complex
ethical issues.[1] Published literature on pharmacotherapy
during pregnancy largely consists of case reports and
observational studies with numerous confounding factors.
Since many pregnancies are unplanned[8] and many
women with mental illness do not experience symptom
improvement during pregnancy, it is important to be
aware about the approaches to and risks associated with
medication treatment during pregnancy. The management
of mental illness in pregnancy requires a sound knowledge
of the psychiatric disease, clinical acumen and perhaps
importantly, common sense.
Research‑based knowledge on the fetal safety of psychotropic
agents is limited since pregnant women have been excluded
from drug trials understandably for ethical reasons.[1]
Hence, we need to rely on animal studies, case reports,
and observational studies for the safety of the medication.
The effects on the fetus to psychotropic exposure can be
classified as teratogenicity, neonatal toxicity, and behavioral
teratogenicity. Several classifications have been proposed
for classifying the teratogenic risks of medications. Among
them are US Food and Drug Administration, the Australian
Drug Evaluation Committee, and the Swedish Catalog of
Approved Drugs. However, these classificatory systems
have limitations in terms of not specifying the dose or
duration of gestational exposure that may be associated
with teratogenic risk.
ISSUES RELATED TO PREGNANCY
The first four embryonic weeks are described as the
period of blastogenesis[2] it is the period of formation of
the blastocyst, implantation and subsequently followed
by the development of primitive streak. The next 4 weeks
that is from 5th to 8th week of gestation is the period of
Access this article online

Address for correspondence: Dr. Prabha S. Chandra, Quick Response Code

Department of Psychiatry, NIMHANS, Bengaluru, Karnataka, India. Website:
E‑mail: chandra@nimhans.kar.nic.in www.indianjpsychiatry.org

How to cite this article: Babu GN, Desai G, Chandra PS. DOI:
Antipsychotics in pregnancy and lactation. Indian J Psychiatry
10.4103/0019-5545.161497
2015;57:303-7.

Indian J Psychiatry 57 (Supplement 2), July 2015 S303

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Babu, et al.: Antipsychotics in pregnancy and lactation
organogenesis.[3] It is during this period that drug exposure
in the mother has maximum effect on the outcome of
pregnancy.
The pharmacokinetics and pharmacodynamics changes
during pregnancy include delayed gastric emptying,
decreased albumin levels (decreased drug‑protein binding),
increased vascular volume hence reduced serum levels
of drugs, enhanced hepatic metabolism and increased
renal clearance, all of which may can significantly affect
drug levels in the body. The fetus has low levels of drug
binding to plasma proteins, immature hepatic metabolism,
a relatively permeable blood brain barrier and difficulties
in transporting drug metabolites back to the maternal
circulation combined with the reduced ability of the fetus
to metabolize drugs to produce higher drug concentrations
in fetal than maternal blood.[3] Hence at one end adequate
levels of medication have to be maintained in the maternal
serum, at the same level it has to be less in the fetal
circulation.
During pregnancy, the placenta serves several critical
physiological functions. Among these is an important barrier
role to minimize fetal exposure to drugs taken by the mother
and other chemicals in the maternal environment.[4] The
fetal‑placental circulation is established by 21 days’ gestation
and is fully formed by the end of the 4th month of gestation.[4]
The protective role of the placenta as a barrier and for removal
of end products of metabolism is vital as the fetal hepatic and
renal systems have immature and insufficient metabolic and
excretory capacity.[5] In a study on placental passage ratio of
antipsychotics medications, highest passage ration was for
olanzapine (mean = 72.1%, standard deviation [SD] =42.0%),
followed by haloperidol (mean = 65.5%, SD = 40.3%),
risperidone (mean = 49.2%, SD = 33.9%), and lowest for
quetiapine (mean = 23.8%, SD = 11.0%).[6] In a recent
study among the atypical antipsychotics quetiapine and
risperidone were relatively good P‑glycoprotein (P‑gp)
substrates whereas, olanzapine showed intermediate affinity
and clozapine showed the least affinity of the drugs studied.[7]
Drugs that are avid substrates of a transporter responsible for
drug efflux (e.g., P‑gp) should have reduced passage across
the placenta; while drugs that are poor substrates of the
efflux transporter will not be affected by this physiological
mechanism and may reach the fetus more easily dependent
upon their lipid solubility, maternal dose, gestational age, and
other disposition‑related variables. Ideally, the drug should
possess a high protein binding, a short elimination half‑life
and a small volume of distribution. Identification of drugs
which interact with placental efflux transporters will allow
the possibility of minimizing fetal exposure in the treatment
of maternal conditions. For pregnancy, future drugs should
be sought which can effectively treat the maternal condition,
all the while minimizing fetal exposure. Ultimately, this may
allow for drugs specifically designed for pregnancy to come
into being.
S304 Indian J Psychiatry 57 (Supplement 2), July 2015
A large number of pregnancies in mentally ill continue to be
unplanned.[8] Hence, the chance of fetal exposure to psychotropic
drugs, especially in the first trimester is high. With current
pharmacological treatment being mostly symptom based,
polytherapy is a rule rather than an exception.[7-9] This in turn
increases the chance of women with unplanned pregnancies
being on multiple drugs. There is ample evidence of an
increase in teratogenicity with polypharmacy (Malm et al., 2003
and 2004; Headley et al., 2004; Peindl et al., 2007).[10-13] Hence
planning pregnancy is of foremost importance in preventing
the fetal exposure to multiple psychotropics.
There has been a decline in birth defects, mainly due to the
introduction of ultrasound screening as part of routine prenatal
care and followed by therapeutic termination of pregnancies.
Primary prevention through folic acid supplementation during
early pregnancy has been found by many epidemiological
studies mostly in preventing neural tube defects.[14] During
the second and third trimesters, many drugs may have
deleterious effects on growth and/or functional development
and toxic effects.[3] Hence, the clinician has to be vigilant
during pregnancy and perinatal period.
ANTIPSYCHOTICS
Antipsychotics are routinely used in treating severe mental
illnesses. Both first generation and second generation
antipsychotics (FGAs and SGAs) are used in the treatment
of serious and severe mental illness.[16]
Second generation antipsychotic agents
Evidence with regard to the safety of atypical antipsychotic
agents is limited, although two recent cohort studies
have revealed no evidence of any increased risk of major
malformations in infants exposed to clozapine, olanzapine,
risperidone and quetiapine.[15]
Many of these agents, however, induce maternal
hyperglycemia, impaired glucose tolerance, weight gain and
increase in birthweight (Newham et al., 2008)[16] all of which
predispose to unfavorable obstetric outcomes and long‑term
maternal complications (Newham et  al., 2001).[16] Studies
have demonstrated increased risk of low birth weight,[17]
while some have shown higher incidence of large for
gestational age (Newham et al., 2008)[16] in infants exposed
to atypical antipsychotics.
Olanzapine is often used in the treatment of severe mental
illness both in schizophrenia and bipolar disorders. This
drug has the increasing data of its use in pregnancy.
Various congenital malformations have been reported after
its use in pregnancy including four cases of neural tube
defects.[18] However, there was the use of concomitant
medication. Furthermore, recent reports of increased birth
weight have been reported with the use of olanzapine
during pregnancy (Newham et al., 2001).[16]
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Babu, et al.: Antipsychotics in pregnancy and lactation
Risperidone is also one of the commonly used SGA.
Reports of congenital anomalies of known typology have
been observed, but there are no recurrent patterns of
anomalies.[19] Perinatal complications have described
with risperidone which range from transient withdrawal
reactions to seizures. Paliperidone which it is chemically
the active metabolite of risperidone, no data concerning
the use of paliperidone in pregnancy is yet available.[18]
One case of the use of long‑acting injectable risperidone in
pregnancy has been reported in the literature, in which the
baby was born normal and healthy and continued to be so
at 8 months of age when the report was done.[20]
More data is available now regarding the use of quetiapine.
Of the 227 reports of pregnancies, there were eight
reports of major malformations of unknown typology
have been observed.[18] In a retrospective chart review,
16 women who were treated with atypical antipsychotics
were analyzed.[21] Among them, quetiapine was the most
frequently prescribed atypical antipsychotic (58.82% of all
exposures) with risperidone, aripiprazole, and ziprasidone
in declining order. Average birth weight was appropriate
for gestational age with one major malformation was noted
which was with the use of aripiprazole.[21]
Little published evidence exists with regard to the
safety profiles of newer agents such as aripiprazole and
ziprasidone, though animal studies have shown teratogenic
effects, delays in skeletal ossification, reduced fetal weight
and increased mortality.[18]
The data on the safety of aripiprazole is limited to case
reports. In one case report, transient unwanted side
effects on the neonatal cardiac rhythm were observed.[18]
There is a lack of human data on the safety of amisulpride,
ziprasidone, and sertindole.
Among SGA, gestational metabolic complications like
gestational diabetes have been observed with use of
olanzapine and clozapine.[18] There is a report of risperidone
induced gestational diabetes. There are reports increased
birth weights in infants with the use of SGA mainly
olanzapine and clozapine.[22]
It is important to monitor the women for gestational
diabetes who are on typical antipsychotics. There is a lack
of information on the long‑term cognitive and behavioral
outcome in the infants exposed to atypical antipsychotics.
First generation antipsychotic agents
With the advent of SGAs, the use of FGA has been limited.
Phenothiazines and butyrophenones have historically been
used to treat hyperemesis gravidarum, nausea, and less
commonly, psychotic disorders in pregnant women. FGA
agents are often prescribed with anticholinergic agents
such as benztropine mesylate or trihexyphenidyl despite
Indian J Psychiatry 57 (Supplement 2), July 2015
the lack of studies on the safety of anticholinergics in
pregnancy.[18]
High‑potency conventional antipsychotic agents such
as haloperidol do not appear to increase the risk of
teratogenicity, whilst low‑potency antipsychotic agents such
as chlorpromazine have a small, but statistically significant
increased risk of nonspecific teratogenic effects with first
trimester exposure.[22‑25] There have been reports of limb
anomalies associated with haloperidol in the first trimester[26]
though larger case series have not supported this.[18]
However, in a survey of more than 50,000 mother‑child pairs
that identified 142 first trimester exposures and 284 total
exposures to chlorpromazine, there was no elevation in the
rate of physical malformations with chlorpromazine.[22] The
same study also suggests that related compounds, including
trifluoperazine, perphenazine, and prochlorperazine, are
similarly not associated with higher than expected rates of
malformations.[22] A meta‑analytic study of first trimester
exposure to low‑potency neuroleptics found an increase
of one case of malformation for every 250 pregnancies in
which exposure occurred.[18]
Transient complications have been documented in the
neonate, including withdrawal symptoms, extrapyramidal
signs (abnormalities of tone and underdeveloped
reflexes), neonatal jaundice and intestinal obstruction.[18]
Extrapyramidal symptoms, including hypertonicity, tremors,
motor restlessness, spasticity, and difficulty with feeding,
have been found in infants exposed to chlorpromazine.[22]
Such symptoms have been reported to last up to 10 months,
but most resolve within days. On the other hand,
hypotonicity can occur in the neonate if the mother’s
dose of chlorpromazine is high.[22] Perinatal complications
associated with the use of haloperidol in late pregnancy
have also been documented.[26] Children with and without
histories of neuroleptic exposure showed no differences in
behavioral functioning or Intelligence Quotient (IQ) when
followed up to 5 years of age.[23]
First generation antipsychotic agents continue to have
a role in the treatment of mania or psychosis during
pregnancy to control acute agitation.[27] There have been
sparse studies looking at drugs and safety of medication for
acute control of agitation and violence. The only attempt
to address this issue was done with the Clinical Consensus
Guidelines published in 2001,[28] who recommend the
use of haloperidol for agitation in pregnant women.
A high‑potency conventional antipsychotic was rated as the
first‑line response by 76% of the consensus panel. The other
second line recommendations were benzodiazepine alone;
risperidone alone; and a combination of a benzodiazepine
and a high‑potency conventional antipsychotic. In a
retrospective study by Ladavac et  al.[27] on 80 pregnant
women, lorazepam was the only benzodiazepine, while
various antipsychotics including haloperidol, risperidone,
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Babu, et al.: Antipsychotics in pregnancy and lactation
ziprasidone, and quetiapine were used for acute control
of agitation. Intramuscular (IM) haloperidol was the most
frequently administered, followed by oral risperidone. The
fetal risk of using several doses of psychotropic medication
to treat agitated pregnant women in the emergency setting
remains unknown. Hence in the above clinical situation
haloperidol IM or oral risperidone can be used to treat
agitation.
Data regarding the safety of fluphenazine, thioridazone,
and promethazine is limited.
ANTIPSYCHOTIC USE DURING THE PUERPERIUM
AND WHILE BREAST‑FEEDING
Breast‑feeding carries many health advantages and is
described as the only nutrition source necessary during the
first 4 months of life.[29] Apart from improved mother‑child
bonding, breastfed babies benefit from lower prevalence
rates of infection and mortality rates.
Women with severe mental illness who relapse during the
immediate postpartum period (or the third trimester) may
require antipsychotic medications. Medication prophylaxis
during the immediate postpartum period should be
considered, although data to support this practice are
available only for treatment with lithium.[18]
The passage of a drug into breast milk is influenced by
many factors including its volume of distribution, molecular
weight, lipid/water solubility, relative affinity for plasma
and milk proteins, the pH of blood and milk (the degree of
ionization of a drug) and blood flow to the breast.[30] An infant
plasma concentration of 10% (or less) of that established as
therapeutic in the mother is considered acceptable and
safe.[31] Safe maternal psychotropic drug dosage limits,
however, remain to be established and in this context, it is
recommended that preterm immature infants should not be
exposed to psychotropic agents. It is also prudent to monitor
breast‑feeding babies for signs of drug‑related toxicity and
adverse effects mainly extrapyramidal symptoms, sedation
and weight monitoring (Yoshida et al., 1998).[32]
First generation antipsychotic agents
These drugs appear safe, evidenced by lactation studies that
have consistently reported milk/plasma ratios of <1, without
evidence of toxic or other adverse effects. Ten reports have
addressed a total of 28 infants’ exposure to antipsychotic
agents through nursing. In the majority of cases, no adverse
events were observed (Yoshida et al., 1997).[32]
Second generation antipsychotic agents
The safety of these drugs remains to be established. Hill
et  al.[31] calculated the estimated infant dose exposure
during breast‑feeding and found that both olanzapine
and risperidone were well below the “attention critical”
S306 Indian J Psychiatry 57 (Supplement 2), July 2015
concentration. Olanzapine[33] and risperidone[34] achieve
very low levels in infant plasma, with no evident adverse
effects, suggesting that these agents may be safe.
The level of infant exposure appears to be similarly
small with quetiapine.[35] Clozapine, however, achieves
relatively high concentrations in breast milk and infant
serum and agranulocytosis and somnolence have been
reported in breast‑fed infants.[36] This agent is therefore
contraindicated during breast‑feeding. Little published
evidence exists with regard to amisulpride, aripiprazole,
and ziprasidone.
GUIDELINES AND CONCLUSIONS
Psychiatric disorders during pregnancy and the postpartum
period are common. Many women are likely to require
treatment for the same during pregnancy. Clinicians are
often apprehensive about treating pregnant women, as
the information on the safety of psychotropics is either
inconclusive or undetermined. With the advent of newer
psychotropics, often minimal data is available, and one has
to keep continuously pace with newer information on drug
safety. Multiple issues have to be considered while choosing
safe treatments for pregnant women, and the best approach
is to individualize treatment. Treatment of these conditions
is important as they can affect the health of the mother and
the fetus/infant. Issues become even more complex with
multiple drugs and if there are associated medical problems
or the infant is premature. Important issues to be kept in
mind include folate supplementation in all women in the
reproductive age group; planning pregnancies to minimize
fetal exposure, discussion with patient and family regarding
options and documentation of all discussions and decisions.
Active liaison with obstetricians, ultrasonologists and
pediatricians need to be stressed, as also the need for local
registries. Whenever possible, use nonpharmacological
approaches in addition. If a psychotropic is necessary, the
choice of medication should be guided primarily by its
safety data during pregnancy and by the psychiatric history
of the patient.
REFERENCES
1. Desai G, Chandra PS. Ethical issues in treating pregnant women with
severe mental illness. Indian J Med Ethics 2009;6:75‑7.
2. Opitz JM. Blastogenesis and the “primary field” in human development.
Birth Defects 1993;29:3‑37.
3. ten Donkelaar HJ, Lammens M, Hori A. Clinical Neuroembryology,
Development and Developmental Disorders of the Human Central
Nervous System. New York: Springer‑Verlag Berlin Heidelberg; 2006.
4. Beck F. Comparative placental morphology and function. Dev Toxicol
1981;35:54.
5. Ganapathy V, Prasad PD. Role of transporters in placental transfer of
drugs. Toxicol Appl Pharmacol 2005;207 2 Suppl:381‑7.
6. Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S,
et al. Atypical antipsychotic administration during late pregnancy: Placental
passage and obstetrical outcomes. Am J Psychiatry 2007;164:1214‑20.
7. Boulton DW, DeVane CL, Liston HL, Markowitz JS. In vitro P‑glycoprotein
affinity for atypical and conventional antipsychotics. Life Sci 2002;71:163‑9.
8. Miller LJ, Finnerty M. Sexuality, pregnancy, and childrearing among women
with schizophrenia‑spectrum disorders. Psychiatr Serv 1996;47:502‑6.
[Downloaded free from http://www.indianjpsychiatry.org on Sunday, March 18, 2018, IP: 117.209.229.140]
Babu, et al.: Antipsychotics in pregnancy and lactation
9. Gregoire A, Pearson S. Risk of pregnancy when changing to atypical
antipsychotics. Br J Psychiatry 2002;180:83‑4.
10. Headley J, Northstone K, Simmons H, Golding J; ALSPAC Study Team.
Medication use during pregnancy: Data from the avon longitudinal study
of parents and children. Eur J Clin Pharmacol 2004;60:355‑61.
11. Peindl KS, Masand P, Mannelli P, Narasimhan M, Patkar A. Polypharmacy
in pregnant women with major psychiatric illness: A pilot study. J Psychiatr
Pract 2007;13:385‑92.
12. Malm H, Martikainen J, Klaukka T, Neuvonen PJ; Finnish Register‑Based
Study. Prescription drugs during pregnancy and lactation – A Finnish
register‑based study. Eur J Clin Pharmacol 2003;59:127‑33.
13. Malm H, Martikainen J, Klaukka T, Neuvonen PJ. Prescription of hazardous
drugs during pregnancy. Drug Saf 2004;27:899‑908.
14. Czeizel  AE, Dudás I. Prevention of the first occurrence of neural‑tube
defects by periconceptional vitamin supplementation. N Engl J Med
1992;327:1832‑5.
15. Dickson RA, Dawson DT. Olanzapine and pregnancy. Can J Psychiatry
1998;43:196‑7.
16. Newham JJ, Thomas SH, MacRitchie K, McElhatton PR,
McAllister‑Williams RH. Birth weight of infants after maternal exposure
to typical and atypical antipsychotics: Prospective comparison study. Br J
Psychiatry 2008;192:333‑7.
17. Littrell KH, Johnson CG, Peabody CD, Hilligoss N. Antipsychotics during
pregnancy. Am J Psychiatry 2000;157:1342.
18. Yonkers KA, Wisner KL, Stowe Z, Leibenluft E, Cohen L, Miller L, et al.
Management of bipolar disorder during pregnancy and the postpartum
period. Am J Psychiatry 2004;161:608‑20.
19. Coppola D, Russo LJ, Kwarta RF Jr, Varughese R, Schmider J. Evaluating
the postmarketing experience of risperidone use during pregnancy:
Pregnancy and neonatal outcomes. Drug Saf 2007;30:247‑64.
20. Kim SW, Kim KM, Kim JM, Shin IS, Shin HY, Yang SJ, et al. Use of long‑acting
injectable risperidone before and throughout pregnancy in schizophrenia.
Prog Neuropsychopharmacol Biol Psychiatry 2007;31:543‑5.
21. Wichman CL. Atypical antipsychotic use in pregnancy: A retrospective
review. Arch Womens Ment Health 2009;12:53‑7.
22. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S.
Antenatal exposure to the phenothiazines in relation to congenital
malformations, perinatal mortality rate, birth weight, and intelligence
quotient score. Am J Obstet Gynecol 1977;128:486‑8.
23. Edlund MJ, Craig TJ. Antipsychotic drug use and birth defects: An
Indian J Psychiatry 57 (Supplement 2), July 2015
epidemiologic reassessment. Compr Psychiatry 1984;25:32‑7.
24. Wisner KL, Perel JM. Psychopharmacological agents and
electro‑convulsive therapy during pregnancy and the puerperium.
In: Cohen PL, editor. Psychiatric Consultation in Childbirth Settings.
New York: Plenum; 1988. p. 165‑206.
25. Trixler M, Tényi T. Antipsychotic use in pregnancy. What are the best
treatment options? Drug Saf 1997;16:403‑10.
26. Van Waes A, Van de Velde E. Safety evaluation of haloperidol in the
treatment of hyperemesis gravidarum. J Clin Pharmacol 1969;9:224‑7.
27. Ladavac AS, Dubin WR, Ning A, Stuckeman PA. Emergency management
of agitation in pregnancy. Gen Hosp Psychiatry 2007;29:39‑41.
28. Allen MH, Currier GW, Hughes DH, Reyes‑Harde M, Docherty JP; Expert
Consensus Panel for Behavioral Emergencies. The expert consensus
guideline series. Treatment of behavioral emergencies. Postgrad Med
2001;48:1‑88.
29. American Academy of Pediatrics Committee on Drugs: The transfer of
drugs and other chemicals into human milk. Pediatrics 1994;93:137‑50.
30. Llewellyn A, Stowe ZN. Psychotropic medications in lactation. J Clin
Psychiatry 1998;59 Suppl 2:41‑52.
31. Hill RC, McIvor RJ, Wojnar‑Horton RE, Hackett LP, Ilett KF. Risperidone
distribution and excretion into human milk: Case report and estimated infant
exposure during breast‑feeding. J Clin Psychopharmacol 2000;20:285‑6.
32. Yoshida K, Smith B, Craggs M, Kumar R. Neuroleptic drugs in breast‑milk:
A study of pharmacokinetics and of possible adverse effects in breast‑fed
infants. Psychol Med 1998;28:81‑91.
33. Gardiner SJ, Kristensen JH, Begg EJ, Hackett LP, Wilson DA, Ilett KF,
et al. Transfer of olanzapine into breast milk, calculation of infant drug
dose, and effect on breast‑fed infants. Am J Psychiatry 2003;160:1428‑31.
34. Ilett KF, Hackett LP, Kristensen JH, Vaddadi KS, Gardiner SJ, Begg EJ.
Transfer of risperidone and 9‑hydroxyrisperidone into human milk. Ann
Pharmacother 2004;38:273‑6.
35. Lee A, Giesbrecht E, Dunn E, Ito S. Excretion of quetiapine in breast milk.
Am J Psychiatry 2004;161:1715‑6.
36. Dev  V, Krupp  P. Adverse event profile and safety of clozapine. Rev
Contemp Pharmacother 1995;6:197‑208.
Source of Support: Nil, Conflict of Interest: None declared
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Clinical Practice Guidelines for Management of Dementia
K.S.Shaji, P.T.Sivakumar1, G. Prasad Rao2, Neelanjana Paul3
Department of Psychiatry, Government Medical College, Thrissur, 1Department of Psychiatry, National Institute of Mental
Health and Neuroscienes, Bangalore, 2Schizophrenia and Psychopharmacology Division, Asha Hospital., Banjara Hills,
Hyderabad, 3Department of Psychiatry, drshajiks@gmail.com
INTRODUCTION
Indian Psychiatric Society (IPS) published Clinical Practice
Guidelines (CPGs) for management of dementia, in the
year 2007. (http://www.indianjpsychiatry.org/cpg2007.asp).
The current version of the CPG is an update of the earlier
version of CPGs for management of dementia There were
three separate CPGs for management of dementia ,one
each for Reversible Dementias, Alzheimer’s Disease and
Vascular Dementia, Please note that the present CPG on
dementia deals all types of dementia together. The current
version of the CPGs for dementia in elderly must be read in
conjunction with the previous version of CPGs for dementia.
The focus of the present CPG is to provide suggestions and
clinical tips to differentiate dementia syndrome from other
clinical conditions, identify the subtypes of dementia and
then offer suggestions for management .
These guidelines only provide a broad framework for
assessment, management and follow-up of older people
with dementia. While most of the recommendations are
evidence based, these guidelines should not be considered
as a substitute of professional knowledge and clinical
judgment. The recommendations made as part of these
guidelines should be tailored to address the clinical needs
of the individual patient and the treatment setting.
AGING, DEPRESSION AND DEMENTIA
Before we examine the management of dementia, let us look
at the issues related to the clinical diagnosis of dementia.
Mental health problems and disablement are frequent in late
life. Dementia and depression are two major mental health
problems in late life . It is well known that the prevalence of
dementia increases steadily with age. Normal aging itself is
associated with age related decline in cognitive functions.
Depressive symptoms are more common in later years of
life. The differentiation between depressive disorder and
a cognitive disorder can be problematic in this age group.
There are many symptoms which can be seen in both in
depressive disorders as well as in cognitive disorders.
Depression can co-exist with mild cognitive impairment
(MCI) a condition which is being increasingly recognized as
an important entity.
S312
MILD COGNITIVE IMPAIRMENT AND
DEMENTIA
Mild cognitive impairment (MCI) is a controversial entity
but remains a useful construct in terms of targeting
interventions to prevent dementia. MCI detection relies
largely on subjective memory complaint (SMC) as a
presenting symptom. However SMC is heterogeneous in its
etiology and poorly predicts medium-term dementia risk.
The differentiation of early dementia from MCI depends on
the level of cognitive impairment and the resultant disability.
Cognitive impairment in dementia causes significant
impairment in instrumental activities of daily living and this
is known to increase with time. Most diagnostic criteria
use the resultant disability as an important differentiating
feature. However reliance on informant reports can be
problematic as that could be influenced by the social
context , expectations of the informant and his or her
ability to know and the current level of functioning of the
older person.
DEMENTIA SYNDROME
Dementia is a syndrome due to disease of the brain, usually
chronic, characterized by a progressive, global deterioration
in intellect including memory, learning, orientation,
language, comprehension and judgment. It mainly affects
older people, after the age of 65 years. Then onwards, the
prevalence doubles with every five year increment in age.
Dementia is one of the major causes of disability in late-life.
People with dementia have difficulty in living independently
and have difficulties in social and occupational functioning.
The disabilities progress with the severity of dementia
Cognitive changes that are part of normal aging process has
to be differentiated from the dementia syndrome. This is
difficult in early stages of dementia. Age related changes
are more frequent in those who are in their eighties and
nineties. Propensity to develop transient cognitive problems
like delirium increases with age and in the presence of
cognitive impairment
Evaluation of cognitive symptoms
Cognitive symptoms can be due to many conditions and
dementia is only one of them. Delineation of the syndrome
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of dementia and differentiating it from other cognitive
disorders is the first task. Other assessments can then
follow. The suggested assessments are best carried out as
part of the initial evaluation though it might take a few
sessions to complete. See table -1 .
Table 1: Assessment for dementia
1) Look for signs and symptoms of dementia
2) Rule out DELIRIUM, DEPRESSION
3) Look for other Medical Problems
4) Assess Cognitive Symptoms
5) Assess Non-Cognitive (Behavioural) and Psychological Symptoms
6) Rule out other Mental Health or Substance use disorders
7) Assess care arrangements and needs of carers
The following assessments will help in making a clinical
diagnosis of dementia : See the flow chart below.
Figure 1: Initial assessment
History of Cognitive Changes
History taking is the main tool in eliciting and evaluating
the nature and progression of cognitive decline. Choose an
informant who knows about the person’s current and past
personal ,social and occupational functioning . A reliable
informant should be interviewed separately in person.
This will allow discussion of a certain information which
may otherwise be difficult in the presence of the patient.
While doing the assessments, one has to be mindful of the
family’s culture, values, primary language, literacy level
and also the decision making process. A thorough history
should include details like the mode of onset of cognitive
decline which affects multiple cognitive domains. The
pattern progression, clinical manifestations of cognitive
dysfunction, behavioral as well as personality changes will
have to be enquired into.
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Subjects or informants can be asked if the person is forgetful
about recent events ;especially amnesia for events which
happened hours or days back. Does the person forget the fact
that he/she had a meal some time after having the meal? Does
the person tend to ask the same questions repeatedly even
though this was answered many times. Is the person unable
to recall where they’ve placed things and often searching
for things? A review of current medication is very important.
Enquire if there is worsening of cognitive symptoms after
initiation of a certain new medication. Details regarding the
use of all medications, including over-the-counter products,
may be collected .See if the person is on medications with
anti-cholinergic effects which can worsen cognitive functions.
Importance of Identification of Delirium
Delirium is an important differential diagnosis of dementia
.Patients with pre-existing dementia could present for the
first time with superimposed delirium. Sudden worsening
of cognitive functions and appearance of behavioural
symptoms should alert the clinician to the possibility of
delirium. Delirium is a medical emergency signs that needs
to be identified early and evaluated immediately.
A diagnosis of dementia cannot be made if the cognitive
deficits occur exclusively during the course of delirium
.Delirium is characterized by a disturbance of consciousness
and a change in cognition that develop over a short period
of time. The disorder has a tendency to fluctuate during the
course of the day, and there is evidence from the history,
examination or investigations that the delirium is a direct
consequence of a general medical condition, substance
intoxication or withdrawal.
The ICD 10 diagnostic criteria for Delirium is given below
ICD 10 CRITERIA FOR DELIRIUM , NOT INDUCED BY
ALCOHOL AND OTHER PSYCHOACTIVE SUBSTANCES
A. Clouding of consciousness, i.e. reduced clarity of
awareness of the environment, with reduced ability to
focus, sustain, or shift attention.
B. Disturbance of cognition, manifest by both:
(1) impairment of immediate recall and recent memory,
with relatively intact remote memory;
(2) disorientation in time, place or person.
C. At least one of the following psychomotor disturbances:
(1) rapid, unpredictable shifts from hypo-activity to
hyper-activity;
(2) increased reaction time;
(3) increased or decreased flow of speech;
(4) enhanced startle reaction.
D. Disturbance of sleep or the sleep-wake cycle, manifest
by at least one of the following:
(1) insomnia, which in severe cases may involve total
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sleep loss, with or without daytime drowsiness, people without pre-existing dementia. The clinician needs
or reversal of the sleep-wake cycle; to differentiate between three possible scenarios namely
(2) nocturnal worsening of symptoms; Delirium with no features suggestive of pre-existing
(3) disturbing dreams and nightmares which may dementia dementia with no features suggestive of delirium
continue as hallucinations or illusions after dementia with superimposed delirium . See table-2 for
awakening. broad guidelines for making this distinction, which by no
means, will be easy in a given clinical setting . When faced
E. Rapid onset and fluctuations of the symptoms over the with uncertainty, it is better to attribute the symptoms to
course of the day. delirium and manage it as delirium.This will allow careful
F. Objective evidence from history, physical and monitoring and detailed evaluation to identify modifiable
neurological examination or laboratory tests of an conditions/factors.
underlying cerebral or systemic disease (other than
psychoactive substance-related) that can be presumed Table-2: Differentiation between Delirium & Dementia
to be responsible for the clinical manifestations in A-D. Delirium Dementia
• Common causes of Delirium include: Onset Usually Abrupt Insidious and progressive
• Infection (e.g. pneumonia, urinary track Comparative features of Delirium and Dementia
infection, etc.) Duration Usually hours to days Months to years
• Drugs (particularly those with anticholinergic Attention Reduced ability to focus, Usually normal except in
side effects e.g. antidepressants, anti- sustain, or shift attention severe dementia
is a hallmark feature that
parkinsonian /anticholinergic drugs, sedatives, occurs early in presentation
etc.) Consciousness (ie, Fluctuating; reduced level Generally intact
• Cardiological (e.g. myocardial infarction, heart awareness of the of consciousness and
failure) environment) impaired orientation
• Metabolic imbalances (e.g. secondary to Speech Often incoherent and Usually coherent, anomia
disorganized or aphasia can be there
dehydration, renal failure) Cause Underlying medical Underlying neurological
• Endocrine and metabolic (e.g. cachexia, condition, substance process (eg, amyloid β
thiamine deficiency, thyroid dysfunction) intoxication, or side-effect plaque accumulation in
• Neurological (e.g. stroke, subdural haematoma, of drugs Alzheimer’s disease)
Epilepsy) Other features Hyperactive, hypoactive, Symptoms vary
and mixed forms, as depending on underlying
• Substance intoxication or withdrawal (e.g. determined by the type of pathology
alcohol) psychomotor disturbance, (eg, fluctuations in
• Respiratory (e.g. pulmonary embolus, hypoxia). are possible; disruption cognition are a feature of
in sleep duration and Lewy body dementia)
architecture; perceptual
Clinician should take care, not to misdiagnose Delirium as
disturbances
Dementia and also not to miss the diagnosis of Delirium
These two syndromes have substantial overlapping in clinical features and
when it is superimposed on dementia. When there is can even coexist in a given patient
clinical suspicion of delirium, the efforts should focus
on identifying the causes. Delirium in older people are Dementia with Psychotic Symptoms and Schizophrenia
most often multifactorial in etiology and identification Presence of BPSD , especially delusions with or without
of the underlying conditions would enable us to provide hallucinations in mild to moderate dementia can resemble
interventions to reverse/modify them. The evaluations need schizophrenia or other psychotic conditions in late life. The
to be comprehensive so that all common causes can be key differentiating features here are history of progressive
ruled out. Prolonged delirium could lead to more neuronal cognitive decline which has onset prior to the development
damage and accelerate cognitive decline by impacting the of psychotic symptoms the presence of clinically significant
cognitive reserve impairment in multiple cognitive domains on clinical
evaluation . This distinction is rather easy when there
The interface between Delirium & Dementia is long duration of illness starting from adulthood. But
Delirium and dementia are two major causes for it could be difficult when psychotic symptoms have onset
cognitive impairment in later years of life. Though these after the age of 60 years and also in situations where it is
two conditions had been conceptualized as distinct , difficult to test cognitive functions due to active psychotic
mutually exclusive entities ,it can be difficult at times to symptoms . One could also come across individuals who
differentiate between them. Delirium in late life is often after many years of illness with onset during adulthood
superimposed on pre-existing dementia and can be the ,either schizophrenia or bipolar disorder , present with
reason for help seeking. Dementia is the leading risk factor cognitive decline and clinical features suggestive of
for delirium in an older person. Occurrence of delirium dementia. In such situations an additional diagnosis of
in turn is a risk factor for subsequent dementia in older dementia can be made apart from the diagnosis of the

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Shaji et al: Management of Dementia

pre existing mental health condition. See table-3 for some The diagnostic challenge in MCI here is in the assessment
clinical tips of “significant impairment in functional ability,” which is
required for the diagnosis of dementia. There is also the
controversy about the best way to objectively measure
Table-3: Psychosis of AD compared with Schizophrenia
memory loss. Early recognition of the condition may help
in the elderly
the clinician to monitor the progression of cognitive and
Clinical Features: Psychosis of AD Schizophrenia
other symptoms and the later conversion to dementia.
Bizarre or complex delusions Rare Frequent
This might allow potential use of evidence based
Misidentifications of caregivers Frequent Rare
Common form of hallucinations Visual Auditory preventive interventions as and when they become
Schneiderian first-rank symptoms Rare Frequent available.The recognition of MCI as a diagnostic allows
Active suicidal ideation Rare Frequent us to have a better understanding of the nature of mild
Past history of psychosis Rare Frequent memory loss ,which is far more common than dementia
Eventual remission of psychosis Frequent Uncommon
among the older segments of the population.Table-4
Need for long-term treatment with Uncommon Very common
antipsychotics lists out the main differences between the two clinical
conditions

Differentiation between Dementia and Mild Cognitive Table-4: MILD COGNITIVE IMPAIRMENT Vs
Impairment DEMENTIA
MILD COGNITIVE DEMENTIA
The differentiation between early dementia and mild IMPAIRMENT
cognitive impairment can be difficult at times but efforts to Impaired cognition in one or more Significant cognitive decline in one
make that distinction is always warranted. DSM 5 uses the domains, but to a lesser degree or more domains- memory ,speech
term Mild Neurocognitive Disorder to refer to this condition. than in dementia. ,judgement, visuospatial, behaviour
ICD 10 does not have specific criteria. The following DSM Mild impairments in the more Substantial impaired cognition
complex aspects of daily
5 criteria may be used as a guide for clinical diagnosis of functioning,
Mild Cognitive Impairment. No significant impairment on Sufficiently severe to interfere
activities of daily living activities of daily living
DSM 5 criteria for Mild Cognitive Impairment Clinical features: Clinical features:
Difficulty in solving complex Severe memory loss
A. Evidence of modest cognitive decline from a previous
problems Visuospatial dysfunction
level of performance in one or more cognitive domains Difficulty in performing more Language problems, articulating
(complex attention, executive function, learning than one task at a time problem
and memory, language, perceptual motor, or social Personality problem
cognition) based on: Prognosis Prognosis
MCI may represent a prodromal Progressive cognitive decline
1. Concern of the individual, a knowledgeable
state of dementia. However, not
informant, or the clinician that there has been a all individuals with MCI will go
mild decline in cognitive function; and on to develop dementia
2. A modest impairment in cognitive performance,
preferably documented by standardized Assessment of Dementia Syndrome
neuropsychological testing or, in its absence, We need to rule out delirium and mild cognitive disorder
another quantified clinical assessment. before we make a clnical diagnosis of dementia . Then one
should apply and see if the person meets the diagnostic
B. The cognitive deficits do not interfere with capacity criteria for Dementia. If that is met, then there is a need to
for independence in everyday activities (i.e., complex make further evaluations. The next part of evaluation is
instrumental activities of daily living such as paying bills aimed at establishing the cause for the dementia syndrome.
or managing medications are preserved, but greater
effort, compensatory strategies, or accommodation Types and Causes of Dementia
may be required). Dementia is a syndrome which can be caused by many
C. The cognitive deficits do not occur exclusively in the diseases .After the clinical recognition of dementia
context of a delirium. syndrome, the evaluations shall focus on identifying the
D. The cognitive deficits are not better explained by cause of dementia. Causes can be broadly classified as
another mental disorder (e.g., major depressive “reversible causes’ and “Irreversible” causes .Though
disorder, schizophrenia). “Reversible” causes are less frequent, they carry good
prognosis with prompt treatment of the underlying
Behavioral disturbance (e.g., psychotic symptoms, mood condition. Thus the evaluation for all potentially reversible
disturbance, agitation, apathy, or other behavioral conditions which cause dementia syndrome is the first most
symptoms important step in the assessment of dementia syndrome

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and this is essential in all cases presenting with features of Vascular dementia, Dementia with Lewy Bodies and Fronto-
dmentia. The type of investigations can be decided based temporal dementia.
on the clinical features and context of care. This aspect
is discussed in detail in the 2009 Dementia Supplement of Table 5:Common Subtypes of Irreversible Dementias
Indian Journal of Psychiatry. Dementia Clinical Features Neuropathology Proportion of
subtype dementia cases
Clinical Assessment Alzheimer’s Impaired memory, Cortical amyloid 50-75%
Patients who seek help in clinical settings often do not represent disease (AD) Apathy and Plaques and
cases prevalent in the community. Reversible causes thus may Depression Gradual neurofibrillary
onset tangles
be much more common in clinical settings than in community Vascular Similar to AD, Cerebrovascular 20-30%
settings. Routine investigations should include complete blood dementia (VaD) but Memory less disease Single
count, erythrocyte sedimentation rate, and serum/blood levels affected, and mood Infarcts in
of urea, electrolytes, calcium and phosphate, liver, renal and, fluctuations more Critical regions,
thyroid function tests, urine analysis, VDRL and Serum Bl2 prominent Physical or more diffuse
frailty Stepwise multi-infarct
,and Folate levels. CT scan or MRI scan, at times, can be a very Progression disease
useful investigation in the differential diagnosis of dementia. Dementia with Marked fluctuation Cortical Lewy <5%
Investigations for testing the HIV status, ECG, Chest radiograph, Lewy Bodies in cognitive ability Bodies (alpha-
Electroencephalogram, Neuropsychological assessment etc are (DLB) Visual Hallucinations synuclein)
investigations worth considering. Parkinsonism (tremor
and rigidity)
Fronto-temporal Personality changes No single 5-10%
Common Potentially Reversible Causes dementia (FTD) Mood changes Dis- pathology –
• Depression inhibition Language damage limited
• Medication Induced (Especially drugs with difficulties to Frontal and
anticholinergic activity) temporal lobes in
the initial stages
• Metabolic derangements
• Thyroid disorders (Hyopthyroidism is a common cause)
Please follow the steps described in Figures 1, 2, 3 and 4 for
• Vitamin B12 deficiency
systematic evaluation of a person presenting with cognitive
• Thiamine deficiency
symptoms
• Chronic disease (e.g., renal failure, hepatic failure,
malignancy)
Cognitive assessment can be made as part of detailed
• Gastrointestinal disorders
examination of higher functions. Commonly used
instruments like Mini-Mental State Examination (MMSE)
• Whipple’s disease
can be used. Addenbrooke’s Cognitive Examination (ACE)
• Vitamin E deficiency
is a more detailed test battery for assessing cognitive
• Pellagra

• Structural brain lesions

• Subdural hematoma
• Normal pressure hydrocephalus
• Tumor

• Infections
• Neurosyphilis
• HIV/AIDS

• How to investigate and rule out Reversible causes?

A reliable ,detailed history will guide us in identifying the
causes of dementia . We have to rule out common reversible
causes and the eminently reversible causes first.See table-5
for the list. Investigations to rule out less common causes
may be needed when the clinical features indicate a high
index of suspicion of reversible dementia.

Dementia syndrome is linked to many underlying causes and

diseases of the brain. The most common causes accounting
for vast majority of cases are due to Alzheimer’s disease, Figure-2: Clinical Assessment: Step 1

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Figure-3: STEP 2: Evaluate Cognitive Impairment
Does the person have poor dietary
intake/malnutrition/anemia?
Figure-4: STEP 3 Evaluation after recognition of the syndrome
of dementia look for medical problems
functions. Assessment of the activities of daily living is
very important. This information is essential in formulating
the individualized plan of intervention. Everyday Activities
Scale for India (EASI) developed during the Indo-US
Cross-National Dementia Epidemiology Study is useful
for this purpose, especially in the rural illiterate. Use
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Shaji et al: Management of Dementia
of simple instruments like the Clinical Dementia Rating
Scale can help in assessing the severity of dementia in
routine clinical practice. Assessment of non-cognitive
symptoms like Behavioural and Psychological Symptoms of
Dementia (BPSD) is yet another important part of clinical
assessment. Two commonly used scales for assessment of
these symptoms are the Neuropsychiatric Inventory (NPI)
and the BEHAVE-AD Both these scales use the caregiver
interview for rating behavioural symptoms. Knowledge of
instruments like MMSE, ACE, EASI, Behave-AD and NPI is
helpful in the detailed and effective assessments of patients
with dementia.
Clinical Criteria for Diagnosis of Dementia
ICD- 10 clinical criteria may be used for diagnosis of
Dementia and subtyping .Alterantively one could use the
DSM-5 criteria too. Since ICD 10 does not give criteria for
Dementia with Lewy Bodies,one could instead rely on the
Consensus criteria or the DSM-5 criteria. You may use the
consensus clinical diagnostic criteria.
After detailed assessment usually, the clinician would be
in a position to judge the cause of the dementing illness.
However at times, even the distinction between Vascular
Dementia and Alzheimer’s Disease (AD) may appear
difficult. Clinical recognition of the subtypes of dementia is
important and is easier during the early part of the illness.
The differentiation between Lewy Body Dementia (LBD),
Frontotemporal Dementia (FTD) and AD can be attempted
during the initial evaluations itself. Such differentiation
is feasible in clinical practice by using clinical criteria for
these subtypes.
The clinicians might choose any standard criteria for
making clinical diagnosis of dementia ,especially common
sub-types. See Table 6 for the criteria which may be useful
in clinical practice
Table 6 : Diagnostic criteria for Dementia
Type of dementia Diagnostic criteria
Alzheimer’s disease See ICD-10 and DSM-5
Vascular dementia See ICD-10 and DSM-5
Dementia with Lewy bodies Revised Consensus criteria for Dementia with
Lewy Bodies
Fronto-temporal dementia Consensus clinical diagnostic criteria for
Fronto-temporal lobar degenration
Please see the description of the suggested clinical criteria below
ICD 10 – DEMENTIA
G1. Evidence of each of the following:
(1) A decline in memory, which is most evident in the
learning of new information, although in more severe
cases, the recall of previously learned information may be
also affected. The impairment applies to both verbal and
non-verbal material. The decline should be objectively
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verified by obtaining a reliable history from an informant,
supplemented, if possible, by neuropsychological tests
or quantified cognitive assessments. The severity of
the decline, with mild impairment as the threshold for
diagnosis, should be assessed as follows:
Mild: a degree of memory loss sufficient to interfere
with everyday activities, though not so severe as to be
incompatible with independent living. The main function
affected is the learning of new material. For example, the
individual has difficulty in registering, storing and recalling
elements in daily living, such as where belongings have been
put, social arrangements, or information recently imparted
by family members.
Moderate: A degree of memory loss which represents a
serious handicap to independent living. Only highly learned
or very familiar material is retained. New information is
retained only occasionally and very briefly. The individual is
unable to recall basic information about where he lives, what
he has recently been doing, or the names of familiar persons.
Severe: a degree of memory loss characterized by the
complete inability to retain new information. Only fragments
of previously learned information remain. The subject fails
to recognize even close relatives.
(2) A decline in other cognitive abilities characterized
by deterioration in judgement and thinking, such as
planning and organizing, and in the general processing of
information. Evidence for this should be obtained when
possible from interviewing an informant, supplemented, if
possible, by neuropsychological tests or quantified objective
assessments. Deterioration from a previously higher level
of performance should be established. The severity of
the decline, with mild impairment as the threshold for
diagnosis, should be assessed as follows:
Mild. The decline in cognitive abilities causes impaired
performance in daily living, but not to a degree making the
individual dependent on others. More complicated daily
tasks or recreational activities cannot be undertaken.
Moderate. The decline in cognitive abilities makes the
individual unable to function without the assistance of
another in daily living, including shopping and handling
money. Within the home, only simple chores are preserved.
Activities are increasingly restricted and poorly sustained.
Severe. The decline is characterized by an absence, or
virtual absence, of intelligible ideation. The overall severity
of the dementia is best expressed as the level of decline in
memory or other cognitiveabilities, whichever is the more
severe (e.g. mild decline in memory and moderate decline in
cognitive abilitiesindicate a dementia of moderate severity).
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G2. Preserved awarenenss of the environment (i.e.
absence of clouding of consciousness (as defined in
F05,criterion A)) during a period of time long enough to
enable the unequivocal demonstration of G1. When there
are superimposed episodes of delirium the diagnosis of
dementia should be deferred.
G3. A decline in emotional control or motivation, or a change
in social behaviour, manifest as at least one of the following:
(1) emotional lability;
(2) irritability;
(3) apathy;
(4) coarsening of social behaviour.
G4. For a confident clinical diagnosis, G1 should have
been present for at least six months; if the period since
the manifest onset is shorter, the diagnosis can only be
tentative.
Comments: The diagnosis is further supported by evidence
of damage to other higher cortical functions, such as
aphasia, agnosia, apraxia.
Judgment about independent living or the development
of dependence (upon others) need to take account of the
cultural expectation and context.
Dementia is specified here as having a minimum duration
of six months to avoid confusion with reversible states with
identical behavioural syndromes, such as traumatic subdural
haemorrhage (S06.5), normal pressure hydrocephalus
(G91.2) and diffuse or focal brain injury (S06.2 and S06.3).
ICD 10
F00 DEMENTIA IN ALZHEIMER’S DISEASE
A. The general criteria for dementia (G1 to G4) must be
met.
B. There is no evidence from the history, physical
examination or special investigations for any other
possible cause of dementia (e.g. cerebrovascular
disease, Parkinson’s disease, Huntington’s disease,
normal pressure hydrocephalus), a sysytemic disorder
(e.g. hypothyroidism, vit. B12 or folic acid deficiency,
hypercalcaemia), or alcohol- or drug-abuse.
Comments: The diagnosis is confirmed by post mortem
evidence of neurofibrillary tangles and neuritic plaques in
excess of those found in normal ageing of the brain.
The following features support the diagnosis, but are not
necessary elements: Involvement of cortical functions
as evidenced by aphasia, agnosia or apraxia; decrease
of motivation and drive, leading to apathy and lack of
spontaneity; irritability and disinhibition of social behaviour;
evidence from special investigations that there is cerebral
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atrophy, particularly if this can be shown to be increasing
over time. In severe cases there may be Parkinson-like
extrapyramidal changes, logoclonia, and epileptic fits.
Specification of features for possible subtypes. Because of
the possibility that subtypes exist, it is recommended that
the following characteristics be ascertained as a basis for
a further classification: age at onset; rate of progression;
the configuration of the clinical features, particularly
the relative prominence (or lack) of temporal, parietal or
frontal lobe signs; any neuropathological or neurochemical
abnormalities, and their pattern.
The division of AD into subtypes can at present be
accomplished in two ways: first by taking only the age
of onset and labeling AD as either early or late, with an
approximate cut-off point at 65 years
ICD 10
F01 VASCULAR DEMENTIA
G1. The general criteria for dementia (G1 to G4) must be
met.
G2. Unequal distribution of deficits in higher cognitive
functions, with some affected and others relatively
spared. Thus memory may be quite markedly affected
while thinking, reasoning and information processing
may show only mild decline.
G3. There is clinical evidence of focal brain damage,
manifest as at least one of the following:
(1) unilateral spastic weakness of the limbs;
(2) unilaterally increased tendon reflexes;
(3) an extensor plantar response;
(4) pseudobulbar palsy.
G4. There is evidence from the history, examination, or
tests, of a significant cerebrovascular disease, which
may reasonably be judged to be etiologically related
to the dementia (e.g. a history of stroke; evidence of
cerebral infarction).
Consensus criteria for FRONTOTEMPORAL DEMENTIA
I. Core diagnostic features
A. Insidious onset and gradual progression
B. Early decline in social interpersonal conduct
C. Early impairment in regulation of personal conduct
D. Early emotional blunting
E. Early loss of insight
II. Supportive diagnostic features
A. Behavioral disorder
1. Decline in personal hygiene and grooming
2. Mental rigidity and inflexibility
3. Distractibility and impersistence
4. Hyperorality and dietary changes
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5. Perseverative and stereotyped behavior
6. Utilization behavior
B. Speech and language
1. Altered speech output
a. Aspontaneity and economy of speech
b. Pressure of speech
2. Stereotypy of speech
3. Echolalia
4. Perseveration
5. Mutism
C. Physical signs
1. Primitive reflexes
2. Incontinence
3. Akinesia, rigidity, and tremor
4. Low and labile blood pressure
D. Investigations
1. Neuropsychology: impairment on frontal lobe
tests without severe amnesia, aphasia, or
perceptuospatial disorder
2. Electroencephalography: normal on
conventional EEG despite clinically evident
dementia
Brain imaging (structural and/or functional): predominant
frontal and/or anterior temporal abnormality
Revised criteria for the clinical diagnosis of probable and
possible dementia with Lewy bodies (DLB)
• Essential for a diagnosis of DLB is dementia, defined as a
progressive cognitive decline of sufficient magnitude to
interfere with normal social or occupational functions,
or with usual daily activities. Prominent or persistent
memory impairment may not necessarily occur in the
early stages but is usually evident with progression.
Deficits on tests of attention, executive function, and
visuoperceptual ability may be especially prominent
and occur early.
• Core clinical features (The first 3 typically occur early
and may persist throughout the course.)
o Fluctuating cognition with pronounced variations
in attention and alertness.
o Recurrent visual hallucinations that are typically
well formed and detailed.
o REM sleep behavior disorder, which may precede
cognitive decline.
o One or more spontaneous cardinal features of
parkinsonism: these are bradykinesia (defined as
slowness of movement and decrement in amplitude
or speed), rest tremor, or rigidity.
• Supportive clinical features
o Severe sensitivity to antipsychotic agents postural
instability; repeated falls; syncope or other transient
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episodes of unresponsiveness; severe autonomic
dysfunction, e.g., constipation, orthostatic
hypotension, urinary incontinence; hypersomnia;
hyposmia; hallucinations in other modalities;
systematized delusions; apathy, anxiety, and
depression.
• Indicative biomarkers
o Reduced dopamine transporter uptake in basal
ganglia demonstrated by SPECT or PET. Abnormal
(low uptake) 123iodine-MIBG myocardial
scintigraphy. Polysomnographic confirmation of
REM sleep without atonia.
• Supportive biomarkers
o Relative preservation of medial temporal lobe
structures on CT/MRI scan. Generalized low uptake
on SPECT/PET perfusion/metabolism scan with
reduced occipital activity 6 the cingulate island sign
on FDG-PET imaging. Prominent posterior slow-
wave activity on EEG with periodic fluctuations in
the pre-alpha/ theta range.
• Probable DLB can be diagnosed if:
o Two or more core clinical features of DLB are
present, with or without the presence of indicative
biomarkers
o Only one core clinical feature is present, but with
one or more indicative biomarkers.
• Probable DLB should not be diagnosed on the basis of
biomarkers alone.
• Possible DLB can be diagnosed if:
o Only one core clinical feature of DLB is present,
with no indicative biomarker evidence
o One or more indicative biomarkers is present but
there are no core clinical features.
• DLB is less likely:
o In the presence of any other physical illness or
brain disorder including cerebrovascular disease,
sufficient to account in part or in total for the
clinical picture, although these do not exclude a
DLB diagnosis and may serve to indicate mixed or
multiple pathologies contributing to the clinical
presentation
o If parkinsonian features are the only core clinical
feature and appear for the first time at a stage of
severe dementia.
DLB should be diagnosed when dementia occurs before or
concurrently with parkinsonism. The term Parkinson disease
dementia (PDD) should be used to describe dementia that
occurs in the context of well-established Parkinson disease.
In a practice setting the term that is most appropriate to the
clinical situation should be used and generic terms such as
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Lewy body disease are often helpful. In research studies in
which distinction needs to be made between DLB and PDD,
the existing 1-year rule between the onset of dementia and
parkinsonism continues to be recommended.
Aassessment of the following will help in planning the
management:
o Activities of Daily Living ( ADL) .This is essentiality
about the the ablity for feeding, bathing, dressing,
mobility, toileting, continence and also the ability to
manage finances and medications
o Assess the Cognitive Status using a reliable and valid
instrument (e.g. the MMSE, MOCA etc)
o Look for other Medical Conditions,Behavioral Problems
, Psychotic Symptoms, or Depressive Symptoms
o Identify the Primary Caregiver: Assess the adequacy of
family and other support systems.
o Assess Caregiver’s needs and risks ; Re-asses this a
regular basis
o Assess the patient’s decision-making capacity and
whether a surrogate has been identified
Assessment of co-morbidity:
Multimorbidity is common in latelife. A clear understanding
of physical aand mental health is important for planning
dementia care. Assess for
a. Co-morbidity
• Depression
• Diabetes/HTN/ Vascular diseases
• Parkinsonism
• Other chronic diseses like COPD/Arthritis
b. Nutritional Status . Poor nutritional status can be a
consequence of poor self care and poor dietary intake
c. Care arrangements
• Identify the Primary caregiver. This is crucial.
In most instances there will be one person who
generally co-ordinates and provide most of the care
provision
• Assess Caregiver support systems
• Is there a Formal/Paid caregiver
• Try to link with local Dementia Society/Palliative
Care service
2. Formulating a treatment plan (Figure 5-8)
• Diagnostic Evaluation. Please follow the earlier
described format to make assessments when there
is history of cognitive decline. Those steps will help
to identify and differentiate between syndromes
like delirium, dementia and mild cognitive disorder.
Once the dementia syndrome is identified the
assessments shall be aimed at the following
• Type of Dementia
• Presence and nature of cognitive and non-cognitive
symptoms
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• Asses Caregiver support

• Assess caregiver needs
• Decide Caregiver interventions
• Provision of Information & Education
• Guidance for management of symptoms of
Dementia
• Caregiver Support
• Decide need for Specific Non-pharmacological
interventions for BPSD
• Decide need for pharmacological methods

Please see table 7 for follow up plans

PROVIDE PSYCHOSOCIAL INTERVENTIONS

Figure-7: Step 6: Management of Dementia

NO worsening of behavioral symptoms

Figure-5: STEP 4 EVALUATE & ADDRESS CAREGIVER

NEEDS

Figure-8: Make Follow-up Plans

• Choice of treatment settings

Figure-6: STEP 5:IDENTIFICATION OF
WHICH NEED SPECIAL ATTENTION
• Home-based care :By and large the commonest setting
for dementia care.The need is to identify and support
the needs of home-based care. Encourage the family
to access/take help from out reach services like
SYMPTOMS community health workers like ASHAs /volunteers of
palliative care services .They may contact local chapters

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Table -7: ASSESSMENTS DURING FOLLOW-UP VISITS
• Look for Side-effects of Medications
If on antipsychotics, check for extrapyramidal symptoms .. Stop or
reduce dose if present.
• Assess for Co-morbid Medical and Mental Health Issues
• Evaluate Activities of Daily Living: See if there is unmet need for
assistance .
• See if there are Mobility Issues / Risk of Fall
• Assess issues related to Safety/ potential for accidents & trauma ;
considerr appropriate interventions like limit driving/ operating
equipment/, cooking, etc.
• Look for emergence of Behavioral Symptoms
• Assess Caregiver Burden / Distress and look for unmet caregiver needs
of Alzhiemer’s and Related Disorders Society, Help
Age India,Paliative Care Networks, other voluntary
agencies engaged in geriatric care and seek support
and guidance
• Institutional care: When the hom-based care is not
feasible or unavailable ,the person with dementia may
need instituitional care with provision for assisted
living
• Short-term hospitalization : This is often required when
there is a medical or surgical morbidity which often
cannot be handled in ambulatory care settings. Onset
of delirium or sudden worsening of BPSD also could
necessitate brief hospitalization. Brief hospitalisations
can be used to provide more information and assistance
to caregivers. This can be an opportunity to identify
unmet care needs as well as needs of the caregivers.
• Long-term assisted living. There is a need for this
facility especially when the home-based care is not able
to meet the demands of care.This is a reality in many
household as the family size is dwindling and most
young people work outside their homes.
Non-pharmacological interventions
Non-pharmacological management strategies( Table -8)
have an important role in the management of dementia
of any type. It is particularly helpful in elderly patients
who may not tolerate pharmacological agents due to the
development of adverse effects even in smaller doses.
There are specific non-pharmacological interventions
targeting the cognitive as well as non-cognitive symptoms
and challenging behaviours seen in dementia.
• Non-pharmacological interventions for cognitive
symptoms
People with mild to moderate dementia of all types
should be encouraged to participate in structured
cognitive stimulation programmes. They benefit
cognition in such patients irrespective of whether any
drug is prescribed or not. They are also beneficial in
improving and maintaining their functional capacity.
This is based on the view that lack of cognitive activity
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hastens cognitive decline. Reality orientation and
reminiscence therapy is of use in this regard.
• Non-pharmacological interventions for non-cognitive
symptoms and challenging behaviour
Non-cognitive symptoms and challenging behaviors
significantly increase the burden of care. They lead
to caregiver distress and burnout and hence is an
important concern in the management of dementia.
Common non-cognitive symptoms seen in dementia
are delusions, hallucinations, anxiety, agitation and
associated aggressive behavior. Challenging behaviours
include a range of difficulties experienced by people
with dementia and has a considerable impact on
their caregivers. Common challenging behaviours are
aggression, agitation, wandering, hoarding, sexual
disinhibition, apathy and shouting.
Non-pharmacological interventions for the non-
cognitive symptoms and challenging behaviours should
be tailored for each patient with participation from
the caregivers.This shall be preceded by assessments
aimed at identifying factors which may be responsible
to generate, aggravate or improve such behaviour. Such
an assessment should be comprehensive and consider
the person’s physical health, possible undetected pain
or discomfort, side effects of medication, psychosocial
factors, cultural and religious background, and physical
environmental factors. Several modalities of non-
pharmacological interventions like aromatherapy,
multisensory stimulation, music/dancing therapy,
massage and animal assisted therapy are available.
The choice of therapy should be made considering the
availability along with the person’s preferences, skills
and abilities. These interventions can be delivered by
health and social care staff and volunteers with proper
training and supervision. The response to each form
of therapy should be monitored and the care plan
should be reviewed from time to time as there may be
individual variations in the response to each of these
modalities.
Pharmacological treatment of Dementia
General Principles
• The pharmacological treatment of dementia is associated
with important challenges such as complexities in the
clinical presentation and diagnosis, non-availability
of therapeutic agents with robust effectiveness and
issues related to tolerability of medications used in the
treatment of dementia.
• Disease modifying drugs to treat Alzheimer’s disease
and other related dementias is an important unmet
need in the treatment of chronic medical disorders in
elderly.
• The currently available options for the pharmacological
treatment of dementia are essentially symptomatic
treatments with limited effectiveness.
• It would be preferable to plan the pharmacological
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Table-8: PSYCHOSOCIAL INTERVENTIONS
1. PROVIDE INFORMATION AND EDUCATION
Ask people assessed with dementia whether they
wish to know the diagnosis and with whom it should
be shared.
• Provide simple explanations of the illness which
they can understand.
• Give only basic information.
Key Messages to be communicated to the
caregivers and the family :
• Dementia is an illness of the brain and that
usually tends to get worse over time.
• Most conditions that cause dementia are
irreversible and thus complete cure is not
possible. But we can do many things help the
person and the family. Guidance will help to
address issues that can arise during dementia
care. Providing support for home based care is
important. Identify and provide information and
education t to primary caregiver/s
3. Promote Activities of Daily living (ADLs) and
Participation in Social Activities
• Encourage independent activity as much as
possible. Assistance could be needed at times.
But, encourage the person to engage in ADLs with
guidance. Offer assistance and encourage to do
the activity with assistance rather than “doing
the task for the person”. This will enhance
functional ability and will allow preservation
and maintenance of skills. This is an important
principle.
• Facilitate social interaction and participation in
community activities. This will help to improve
the quality of life of people with dementia and
their corers. Instruct the caregivers to be socially
active and remain networked with friends and
other family members. They should try and
actively prevent getting socially isolated
• Give advice to maintain independent toileting
skills
• Keep the environment at home safe to reduce the
risk of fall / injury.
• Recommend making adaptations in the person’s
home. Eg. Having hand-rails or ramps could help.
• Engagement in regular physical activity and
exercise may help to maintain mobility and
reduce risk of falls.
• Advise recreational activities (tailored to the stage
and severity of dementia).
• Manage sensory deficits (such as low vision or
poor hearing) with appropriate devices.
• Assist in getting help from available social
resources
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4. Interventions to Improve Cognitive Functioning
• A cognitively stimulating environment will allow
best use of cognitive abilities.
• Caregivers may be instructed to include
orientation information (e.g. day, date, time,
names of people) during conversations .Such
conversational style will help the person to
remain oriented. Co-resident family members
and close associates can keep this in mind during
social interactions. At the same time do not over
do this. Do not attempt to test the person’s
memory or orientation . Just provide cues when
appropriate
• Materials such as newspapers, radio, or TV
programmes can help to orient to current events.
• Photos and household items can be used to
promote communication. These can stimulate
memories, and encourage the person to talk
about past experiences
• It is important to use simple language for
communicating. Short sentences will make verbal
communication clear and unambiguous. Listen
carefully to what the person has to say.
• Keep things simple, avoid changes to routine as
far as possible
• Exposure to unfamiliar ,crowded environments
can cause and fear.
5. Offer support for Caregivers.
• Assess current care arrangements.
• Identify the main caregivers and assess the impact
of caregiving.
• Look for caregiver distress ; look for depressive
symptoms in the caregiver
• Acknowledge that carers often experience
difficulties during the care of people with
dementia and that that stress is a common
experience.
• Encourage the care givers to seek help and
support when they experience difficulty or strain
• Provide adequate information about dementia
and dementia care to all caregivers. Use leaflets
hand outs for informing careers and their families
• Provide specific information and guidance to
manage behavioral symptoms, issues related to
incontinence and co-morbid medical problems.
• Advise caregivers to get support whenever
feasible.
• Encourage the option of getting another caregiver
to substitute the primary caregiver periodically.
This will allow relief to the primary caregiver
who then can engage in other activities.
• Explore whether the person qualifies for any
disability benefits or other social/financial support
(government or non-governmental).
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treatment of dementia after comprehensive evaluation
to understand the possible subtype, associated
behavioural and psychological symptoms, comorbidity
etc
• Treatment of dementia needs to be focused on
improving the cognitive function, amelioration of
associated behavioral and psychological symptoms and
improvement or stabilization of global functioning in
daily activities.
• It would be useful to have clear understanding of the
treatment targets and proper monitoring of outcomes
following treatment to optimize the treatment
appropriately(Figure-9).
• Behavioral and psychosocial interventions are required
for all patients with dementia. Pharmacological
treatment needs to be planned in addition to this
particularly for behavioral and psychological symptoms
of dementia.
Figure-9
Pharmacological treatment for cognitive symptoms of
Dementia(Tables 9 & 10)
• Alzheimer’s disease is the most common cause of
dementia and a major contributor for global disease
burden. Hence there has been very active global
effort to develop effective disease modifying drug for
Alzheimer’s disease in the past decade.
• However, no new effective drug has been identified
for improving the cognitive function in patients with
dementia due to Alzheimer’s disease in the last decade.
• Cholinesterase Inhibitors (Donepezil, Rivastigmine and
Galantamine) and NMDA antagonist (Memantine) are
the approved pharmacological treatment options for
the cognitive impairment in Alzheimer’s Dementia
• Donepezil has been approved for all stages of
Alzheimer’s dementia. Rivastigmine and Galantamine
has been approved for mild to moderate Alzheimer’s
dementia
• Memantine has been approved for moderate to severe
Alzheimer’s dementia
• Combination of Donepezil and Memantine has been
approved for moderate to Severe Alzheimer’s dementia
• Rivastigmine Transdermal patch (4.6mg, 9.5mg or
13,3mg per 24 hours) has been approved for mild to
moderate Alzheimer’s dementia. The extent of adverse
effects with Rivastigmine is lesser in transdermal patch
than oral formulation.
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• There is no clear evidence regarding the benefit of
Cholinesterase inhibitors for the management of
behavioral and psychological symptoms in Alzheimer’s
dementia.
• The efficacy of cholinesterase inhibitors is established
clearly in the short term randomized controlled trials
lasting for 3 to 6 months for the cognitive domains and
global functioning.
• Few studies have indicated continued benefit of
cholinesterase inhibitors in the long term (up to 1 year).
But there are limitations in the quality of this evidence.
• The benefit of cholinesterase inhibitors in the long term
is suggested through the observation of deterioration
of cognitive function and global functioning after the
withdrawal of cholinesterase inhibitors.
• The adverse effects that are commonly noted to occur
with Cholinesterase inhibitors are primarily related
to cholinergic effects (nausea, vomiting, diarrhea,
anorexia, weight loss, bradycardia and falls).
• The most common adverse effects with cholinesterase
inhibitors are gastrointestinal side effects. The
cholinergic effects are usually dose related. The
tolerability appears to improve with dose reduction
and slower titration.
• The benefit with cholinesterase inhibitors is difficult
to establish at individual patient level in view of the
progressive nature of the illness and the possibility of
contribution to cognitive decline from multiple factors.
• The assessment of response to treatment is based on the
effects on cognitive symptoms, activities of daily living
and the clinician judgement about the global change.
• Memantine can be considered as the choice of drug for
treatment of patients with Alzheimer’s dementia when
cholinesterase inhibitors are contraindicated or could
not be tolerated due to adverse effects.
• Despite the minor differences in the mechanism of
action of Donepezil, Rivastigmine and Galantamine,
there is no clear evidence to support choosing any
specific cholinesterase inhibitor over other drugs.
• It would be useful to do Electrocardiogram to rule out
conduction abnormalities and clarify about pre-existing
gastrointestinal side effects like nausea and vomiting
prior to initiating cholinesterase inhibitors.
• Patients initiated on medications for dementia requires
follow up evaluation after 4 to 6 weeks to review the
adverse effects and adjust the dose as required.
• If a patient is not tolerating one cholinesterase inhibitor
and it has not improved with dose reduction or slower
titration, changeover to another cholinesterase
inhibitor can be considered.
• Rivastigmine transdermal patch can be considered if
there are significant gastrointestinal side effects with
oral cholinesterase inhibitor.
• High dose (11.5 and 23mg) extended release Donepezil
has been approved for use in moderate to severe dementia
after 3 months of stabilization with 10mg Donepezil.
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• The approval for Donepezil 23mg is based on a single
randomized controlled trial which showed that it was
significantly better than Donepezil 10mg for improving
cognitive function in patients with moderate to severe
Alzheimer’s dementia.
• The clinical utility of Donepezil 23mg is not clear as the
marginal improvement in cognitive function without
significant improvement in global functioning may
have limited clinical significance for individuals with
moderate to severe dementia.
• The frequency of cholinergic adverse effects is also
higher with Donepezil 23mg contributing to poor
tolerability and increased risk for discontinuation
• Other than cholinesterase inhibitors and memantine,
there are no other approved drugs to improve
cognitive function in patients with dementia. Cognitive
enhancers like Ginko Biloba and Piracetam do not have
clear evidence to be recommended for routine use in
patients with dementia.
Pharmacological treatment for Behavioural and
Psychological symptoms of dementia (Table 11)
• Behavioral and Psychological symptoms of dementia
(BPSD) is very common in patients with dementia.
Nearly all patients with dementia are likely to develop
BPSD at any point of time during the illness.
• BPSD is often the most important contributor for the
distress and burden in caregivers. Many patients with
dementia are brought for evaluation and treatment
primarily due to BPSD.
• BPSD is also the important factor that determines the
risk for institutionalization.
• Apathy, depression, agitation, aggression, wandering
behavior, sleep disturbance and psychotic symptoms
are the most common BPSD symptoms in dementia.
• Risperidone is the only treatment approved for the
treatment of agitation and aggression in patients with
dementia.
• Use of antipsychotics in elderly with dementia is
associated with increased risk for cerebrovascular
adverse events and mortality
• Pharmacological treatment for BPSD needs to be
considered only if the symptoms are distressing to the
patient / caregiver or if it is contributing to the risk for
harm to patient / others.
• Recent evidence has suggested the possibility of
improvement in agitation with Citalopram when it is
not severe enough to initiate antipsychotics.
• Like Citalopram, other Selective Serotonin Reuptake
Inhibitors (SSRI) are also likely to be effective in controlling
the agitation in patients with dementia. However, there is
need for more evidence to support this treatment option.
• Higher dose of Citalopram (used in the study showing
positive effect on agitation in dementia) is associated
with increased risk for QT interval prolongation. Hence
it is not recommended.
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• Low dose atypical antipsychotics (Aripiprazole,
Risperidone, Quetiapine etc) can be considered for
severe psychotic symptoms and agitation
• Quetiapine and Clozapine can be considered by severe
psychotic symptoms in dementia due to Lewy body
disease and Parkinson’s disease
• Treatment with SSRI and Mirtazapine has not contributed
to significant improvement of depression in patients
with dementia.
Pharmacological Treatment in Non-Alzheimer’s dementia
• Clinical trials on the treatment of dementia has
largely focused on Alzheimer’s dementia due to high
prevalence and public health significance
• There is no clear evidence for efficacy of cholinesterase
inhibitors or memantine in Vascular dementia and
Frontotemporal dementia
• Cholinesterase inhibitors (Particularly Rivastigmine
and Donepezil) have significant benefits for cognitive
symptoms as well as visual hallucination in dementia
due to Lewy body disease and Parkinson’s disease
• SSRI and Trazodone are found to be useful in
Frontotemporal dementia
• Lorazepam or Clonazepam and Melatonin are found
to be useful for REM sleep behavioural disorder in
dementia due to Lewy body disease.
• Patients with Vascular dementia needs treatment with
medications for risk factors like diabetes, hypertension,
dyslipidemia etc
• Cholinesterase inhibitors can be tried in patients with
mixed dementia if Alzheimer’s disease is co-existent
with other types of dementia
Other Somatic treatments
• Electroconvulsive therapy (ECT) can be considered for
severe depression in patients with dementia.
• ECT can be considered for those with dementia having
very severe agitation and aggression that are non-
responsive to other treatments
• Non-invasive brain stimulation like Transcranial
direct current stimulation (tDCS) and Transcranial
Magnetic Stimulation (TMS) have no clear evidence of
effectiveness in patients with dementia.
Table- 9: Pharmacological Treatment of Dementia
• Cholinesterase Inhibitors (Donepezil, Rivastigmine and Galantamine )
can be used for all the stages of Dementia due to Alzheimer’s disease
• Memantine alone or in combination with Cholinesterase inhibitors is
useful in moderate to severe Dementia due to Alzheimer’s disease
• Donepezil and Rivastigmine can be used in Dementia due to Lewy
Body disease and Parkinson’s Disease
• Selective Serotonin Reuptake Inhibitors can be used in Frontotemporal
dementia
• Low dose atypical antipsychotics (Risperidone, Aripiprazole,
Quetiapine) can be considered for severe agitation, aggression and
psychotic symptoms
• Mood Stabilizers like Divalproex sodium and Carbamazepine may be
useful in the management of agitation
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Table -10: Approved Antidementia drugs Table 11: Psychotropic Agents Useful for the Treatment
Name of the Usual Maximum Side effects Remarks of BPSD
Drug Starting recommended Type and Drug Initial Final Daily Dose Targeted Symptoms
dose in dose (mg/day) Daily (Range)
mg/day Dose
Cholinesterase Inhibitors Atypical antipsychotic
Donepezil 5 10 Nausea, Start with 5mg
vomiting, once daily Risperidone 0.5 mg 1.0 mg Psychosis and
diarrhea, and increase daily (0.75 -1.5 mg daily) agitation
insomnia, to 10mg once
muscle cramps, daily after Olanzapine 2.5 mg 5.0 mg
anorexia, 4 weeks if daily (5-10 mg daily
weight loss, tolerability is Quetiapine 25 mg 200 mg
bradycardia, good daily (50-150 mg twice a day)
syncope Mood stabilizer
Rivastigmine 3 12 Similar side Start with Divalproex 125 mg 500 mg Agitation
effects like 1.5mg twice sodium twice a (250-500 mg twice a day)
Donepezil daily and m day
but slightly increase by Carbamazepine 200 mg 400 mg
more severe 3mg per day twice a (200-500 mg twice a day)
gastrointestinal every 2 weeks day
side effects till 6mg twice Selective serotonin-reuptake inhibitor
daily Citalopram 10 mg 20 mg Depression, anxiety,
Galantamine 8 24 Similar to Start with 4mg daily (20-40 mg daily) psychosis, and
Donepezil and twice daily Escita!opram 5 mg 10 mg agitation
Rivastigmine and increase daily (10-20 mg daily)
by 8mg every Paroxetine 10 mg 20 mg
4 weeks till daily (10-40 mg daily)
12mg twice Sertraline 25 mg 75 mg
daily daily (75-100 mg daily)
Rivastigmine 4.6mg/ 24 9.5mg/24 Occasional Start with
Transdermal hours patch hours patch Skin Irritation 4.6mg/24hours
patch patch and
increase to
• Disease modifying drugs for dementia are expected to
9.5mg/24 be more effective in the stage of MCI compared to the
hours patch stage of dementia.However no effective medication has
after 4 weeks been identified for MCI
if tolerability is
• Acetyl Cholinesterase inhibitorsand Memantine have
good
Donepezil 11.5 23 More severe Titration to not been found to be effective in delaying the conversion
Extended gastrointestinal high dose of MCI to dementia. Routine use of Cholinesterase
Release side effects Donepezil inhibitors or Memantinefor the treatment of MCI is not
needs to be recommended.
considered
after at least
(Please see references 12-20 for further reading of
3 months pharmacological treatment)
maintenance Management of different phases of illnesses
with 10mg
Donepezil
The course of Dementia can be divided into three phases;
NMDA
Antagonist mild, moderate and severe, based on the severity of
Memantine 10 20 No significant Start with 5mg cognitive symptoms and functional impirment. Symptoms
adverse effects twice daily like BPSD are more common in the mild to moderate phase
and increase where as the impairments in ADL predominate the severe
by 5mg every
phase.BPSD may not be present in all cases and may not be
week and
titrate to 10mg problematic in some. Mangement of BPSD is particularly
twice daily important during the initial phases of the illness as this
can have direct impact on the quality of life of the affected
individual and the family members involved in care. Refer
Pharmacological Treatment of Mild Cognitive Impairment to the setion on management
• Mild Cognitive Impairment (MCI)is the high-risk state
for dementia with significantly increased risk for Special Issues in the management of Dementia
conversion to dementia compared to those with normal 1. Delirium Superimposed on Dementia
cognition. • When to suspect ?

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Older people with dementia have high risk of development
delirium. Both hypoactive and hyperactive delirium can
occur , but hypoactive delirium is more likely. Any sudden
deterioration in sensorium ,activity level, behaviour should
alert the possibility of superimposed delirium. It will be be
associated with disturbance in sleep wake cycle and could
also take the form of increased sleepiness.
• How to manage?
The management should involve attempts to identify
multiple causes which usually contribute to development
and persistence of delirium .Once identified these factors
may be addressed and the condition be monitored.
Disappearance of recent onset behavioural symptoms and
improvement in cognitive functions over a period of days
would usually be indicative of resolution of superimposed
delirium
2. Management of Multi-morbidity.
Dementia is a major neuropsychiatric condition and long-
term medical care. Multimorbidity is common among older
people and people with dementia are no exception. Two
strategies can help here. The first one is to evaluate the
person in detail for presence of co-morbidity and sensory
impairments.This can be done after making the diagnosis
of dementia. Do enquire about the current management of
each problem. You may include the management of the co-
morbid conditions also into the follow-up plan.The second
important strategy would be to be on the watch out for
emergence of new problems like delirium or issues related
falls , infections, cerebrovascular events etc. Prompt
identification and early interventions can help to prevent
or identify major eventsearly. Adherence to interventions
is a matter of concern as this would be dependent on
the caregivers. Communication with the caregivers will
have to be simple and might need to be repeated. Try to
speak to the primary caregivers directly and allow time for
clarifications if they have doubts. Ask a family member to
take up the responsibility of co-ordinating and monitoring
home-based care and to report the progress during follow
up visit. The primary caregiver is the ideal person to do this.
Frequent changes in place/caregivers etc can create issues
and is best avoided minimised. But resource limitations
are frequent and providing more caregiver support during
trying times can be a great help for families involved in
dementia care
3. Risk of Falls/fractures :
Prevention of accidents/trauma particularly falls is important.
Judicious modification of the home environment will help.
An informed caregiver can discuss this and do the needful.
Discussions with caregivers and other family members will
allow innovations which will may suit the particular home
setting. All falls increase the risk of fractures and a fracture
hip can have a very negative outcome for an older person
with dementia
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4. Need to Link with Community-based Services
It would help if community outreach services like palliative
care services or any other similar service can be linked to
home-based dementia care
5. Use of diagnostic instruments/tools
Brief screening tests can be useful ..This can help in eliciting
key information and by making brief cognitive assessment.
The ideal test would be sensitive and specific. It should be
short, simple and user friendly. There are large number of
tests available and that suggests that no one test is the best.
Shorter tests may confirm a cognitive problem that needs to
be evaluated, whereas longer tests contribute more to the
diagnosis. There are many instruments useful to screen or
find cases of dementia. See http://www.who.int/mental_health/
mhgap/evidence/dementia/q6/en/index.html for more details of
the review. Details of useful tools are available at the website
of Alzheimer’s Association( https://www.alz.org/documents_
custom/141209-CognitiveAssessmentToo-kit-final.pdf)
CONCLUSIONS
Caregiver support and non-pharmacological interventions
to manage symptoms like BPSD are the main ingredients of
dementia care. Psychosocial management forms the first line
and shall be given to all with BPSD. Psychosocial interventions
work best when it is contextualized to the socio-cultural
environment and the setting of care. Family and professional
caregivers should be considered as key collaborators. Provision
of relevant information , education and seamless support to
caregivers , will be very crucial in dementia care. There is
unmet need for such help and guidance .The families engaged
in the care of a person affected by dementia will benefit from
such support and this is especially so there are behavioral
symptoms which are difficult to mange in home setting Some
may benefit from pharmacological interventions but this shall
be provided under supervision and needs to be monitored.
REFERENCES
1. Stewart R. Mild cognitive impairment--the continuing challenge of its “real-
world” detection and diagnosis. Arch.Med.Res. 2012;43(8):609-14
2. Tripathi M, Vibha D. Reversible dementias. Indian J Psychiatry. 2009
Jan;51Suppl 1:S52-5. PubMed PMID: 21416018; PubMed Central
PMCID: PMC3038529.
3. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical
method for grading the cognitive state of patients for the clinician. J
Psychiatr Res.1975 Nov;12(3):189-98. PubMed PMID: 1202204.
4. Mathuranath PS, Nestor PJ, Berrios GE, Rakowicz W, Hodges JR.
A brief cognitive test battery to differentiate Alzheimer’s disease and
frontotemporal dementia. Neurology 2000
5. Fillenbaum GG, Chandra V, Ganguli M, et al. Development of an activities
of daily living scale to screen for dementia in an illiterate rural older
population in India. Age Ageing 1999; 28:161 -8
6. Morris JC.The Clinical Dementia Rating (CDR): current version and
scoring rules. Neurology 1993;43:2412-4.
7. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA,
Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment
of psychopathology in dementia. Neurology 1994;44:2308-14
8. Reisberg B, Borenstein J, Salob SP, Ferris SH, Franssen E, Georgotas
A. Behavioral symptoms in Alzheimer’s disease: phenomenology and
treatment. J Clin Psychiatry 1987; 48:9-15
9. McKeith IG, Boeve BF, Dickson DWet al Diagnosis and management
S327
[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]

Shaji et al: Management of Dementia

of dementia with Lewy bodies: Fourth consensus report of the DLB • See Dementia Module of mhGAP Intervention Guide of WHO www.who.
Consortium. Neurology. 2017 Jul 4;89(1):88-100 int/mental_health/mhgap/mhGAP_intervention_guide_02/en/
10. American Psychiatric Association. Diagnostic and Statistical Manual 5th • https://www.mja.com.au/journal/2016/204/5/clinical-practice-guidelines-
edition. Arlington, VA: APA 2013 dementia-australiawww.ipa-online.org/- international psychogeriatric
11. Benson Kertesz, P. H. Robert, M. Albert, K. Boone, B. L. Miller, J. association
Cummings and D. F. D. Neary, J. S. Snowden, L. Gustafson, U. Passant, • https://www.ipa-online.org/publications/guides-to-bpsd- IPA Complete
D. Stuss, S. Black, M. Freedman, A. F Frontotemporal lobar degeneration: Guides to Behavioral and Psychological Symptoms of Dementia (BPSD)
A consensus on clinical diagnostic criteria Neurology 1998;51;1546-1554
12. Farooq, M. U., Min, J., Goshgarian, C., &Gorelick, P. B. (2017).
Pharmacotherapy for Vascular Cognitive Impairment. CNS Drugs, 31(9), RESOURCES FOR INFORMATION TO THE
759-776. doi:10.1007/s40263-017-0459-3 CAREGIVERS
13. Kales, H. C., Gitlin, L. N., &Lyketsos, C. G. (2015). Assessment and
management of behavioral and psychological symptoms of dementia.
BMJ : British Medical Journal, 350. doi:10.1136/bmj.h369 • Alzheimer’s Disease International https://www.alz.co.uk/
14. Kobayashi, H., Ohnishi, T., Nakagawa, R., &Yoshizawa, K. (2016). The • Alzheimers and Related Diseases Society of India https://www.ardsi.org/
comparative efficacy and safety of cholinesterase inhibitors in patients
with mild-to-moderate Alzheimer’s disease: a Bayesian network meta-
analysis. Int J Geriatr Psychiatry, 31(8), 892-904. doi:10.1002/gps.4405
15. Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S. G., Huntley, J.,
Ames, D., . . . Mukadam, N. (2017). Dementia prevention, intervention, and This is an open access article distributed under the terms of the Creative
care. Lancet, 390(10113), 2673-2734. doi:10.1016/S0140-6736(17)31363-6 Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
16. Matsunaga, S., Kishi, T., & Iwata, N. (2014). Combination therapy with others to remix, tweak, and build upon the work non‑commercially, as long as the
cholinesterase inhibitors and memantine for Alzheimer’s disease: a author is credited and the new creations are licensed under the identical terms.
systematic review and meta-analysis. Int J Neuropsychopharmacol, 18(5).
doi:10.1093/ijnp/pyu115 For reprints contact: reprints@medknow.com
17. O’Brien, J. T., Holmes, C., Jones, M., Jones, R., Livingston, G., McKeith,
I., . . . Burns, A. (2017). Clinical practice with anti-dementia drugs:
A revised (third) consensus statement from the British Association Access this article online
for Psychopharmacology. J Psychopharmacol, 31(2), 147-168. Quick Response Code
doi:10.1177/0269881116680924 Website:
18. O’Brien, J. T., & Thomas, A. (2015). Vascular dementia. Lancet,
386(10004), 1698-1706. doi:10.1016/s0140-6736(15)00463-8 www.indianjpsychiatry.org
19. Stinton, C., McKeith, I., Taylor, J. P., Lafortune, L., Mioshi, E., Mak, E.,
. . . O’Brien, J. T. (2015). Pharmacological Management of Lewy Body
Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry, DOI:
172(8), 731-742. doi:10.1176/appi.ajp.2015.14121582
20. Walker, Z., Possin, K. L., Boeve, B. F., &Aarsland, D. (2015). Lewy 10.4103/0019-5545.224472
body dementias. Lancet, 386(10004), 1683-1697. doi:10.1016/s0140-
6736(15)00462-6

WEBSITES FOR FURTHER INFORMATION How to cite this article: Shaji KS, Sivakumar PT, Rao GP,
Paul N. Clinical Practice Guidelines for Management of
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Clinical Practice Guidelines for Management of Depression in Elderly
Ajit Avasthi, Sandeep Grover
Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh. Correspondence:
drajitavasthi@yahoo.co.in
Other Expert participants: Shrikant Srivastava, Ajit Bhide,
Naresh Nebhinani, P K Dalal
INTRODUCTION
Depressive disorders are one of the common psychiatric
ailments seen in elderly population. As per the World Health
Organization (WHO) prevalence of depressive disorders
among elderly is 10 to 20%. Data from India reveals a wide
variation in the prevalence rate of depression. Prevalence in
community-based studies have varied from 8.9% to 62.16%
and clinic based studies have estimated the prevalence
of depression to range from 42.4 to 72%. Unfortunately,
depression among elderly is often considered as part and
parcel of life and is under-recognised and under-diagnosed.
Depression in elderly has been shown to be associated
with significant negative consequences ranging from poor
quality of life, difficulties with activities of daily living,
physical comorbidities, premature mortality and cognitive
impairments. Although the incidence of depression among
elderly is similar to that reported in adult population,
depression in elderly is associated with higher risk of
suicide, more frequent hospitalization, higher number
of consultations with the treatment agencies and family
burden. Hence, it is very important to recognise depression
among elderly and manage the same.
Timely recognition and adequate management of depression
among elderly can lead to improvement in quality of life,
maintaining optimal levels of function and independence,
reduction in morbidity, reduction in mortality due to suicide,
development of medical illnesses and treatment costs.
Indian Psychiatric Society (IPS) published Clinical Practice
Guidelines (CPGs) for management of depression among
elderly, for the first time in the year 2007. IPS also published
revised CPGs for management of depression in adult patients
in the year 2017. Current version of the CPGs is an update of
the earlier version of CPGs for management of depression
in elderly. The current version of the CPGs for depression
in elderly must be read in conjunction with the previous
version of CPGs for depression in elderly and revised CPGs
for management of depression in adult population.
These guidelines provide a broad framework for assessment,
management and follow-up of elderly patients presenting
© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
with depression. Most of the recommendations made
as part of the guidelines are evidence based. However,
these guidelines should not be considered as a sustitute
for professional knowledge and clinical judgment. The
recommendations made as part of these guidelines have to
be tailored to address the clinical needs of the individual
patient and treatment setting.
DIAGNOSTIC COMPLEXITIES OF DIAGNOSING
DEPRESSIVE DISORDERS IN ELDERLY
Depressive disorders in elderly can include a spectrum of
disorders (Table-1). Depression in elderly is also known
as late life depression, which is further understood
as late onset depression and early onset depression.
There is lack of consensus on the age cut-off used to
define late onset depression, with some of the authors
considering the age cut-off of 60 years, whereas others
define it as experiencing first episode of depression
≥ 65 years of age). While assessing depression among
elderly, it is important to remember that although many
elderly have depressive symptoms, they do not fulfil
the criteria of major depression. Presence of physical
illness and atypical presentations further complicate the
clinical picture. Hence it is postulated that although the
presence of standard diagnostic criteria is a necessary for
of depression in elderly, this is not sufficient condition
for diagnosis of depression in elderly. Due to these
intricacies, the concept of ‘subthreshold’ depression,
‘subclinical’ depression, ‘minor’ depression, ‘milder’
depression etc have been described. Accordingly,
depression in elderly is often broadly classified as Major
and Non-major Depression. The nonmajor category
includes minor depression, dysthymia, adjustment
disorder with depressed mood and mixed anxiety and
depressive disorder.
In general it is suggested that prevalence of minor
depression is more than that of major depression. Some
of the studies suggest that with increasing age prevalence
of major depression decreases and that of minor or sub-
threshold depression increases. Minor depression in elderly
is associated with significant number of disability days and
concomitant anxiety disorder. Proper recognition of minor
depression is of paramount importance because it is often
the forerunner of the major depression among elderly
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Avasthi and Grover: Management of Depression in Elderly
subjects. The spectrum of depressive disorders among
elderly also includes dysthymic disorder and adjustment
disorder with depressed mood, which are also seen in 2%
and 4% of the population respectively.
Minor depression is defined as presence of clinically
significant depressive symptoms which do not meet the
threshold duration criterion or the number of symptoms
necessary for the diagnosis of Major depressive disorder
(MDD) as per the current nosology. Some of the authors have
further characterised minor or subsyndromal depression
among elderly into 2 subtypes. According to some authors
the first subtype of minor depression consists of syndromes
qualitatively similar to major depression and dysthymia but
it is characterised by presence of fewer symptoms or with
less symptom continuity. The second type of subsyndromal
depression is considered to be qualitatively different from
MDD and is associated with lower suicidal thoughts and
feelings of worthlessness or guilt but similar levels of
worries about health and “weariness of living”. Judd et
al described 2 subtypes of subsyndromal symptomatic
depression (SDD) for minor depression as SDD with mood
disturbance (minor depression) and SDD without mood
disturbance.
Minor depression was described in the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) as a
condition requiring further research to determine both
diagnostic utility and criteria refinement. In DSM-5, minor
depression can be subsumed under the category of “Other
specified depressive disorder, depressive episode with insufficient
symptoms”, which is characterised by presence of depressed
affect and at least one of the other eight symptoms of MDD,
which is associated with clinically significant distress or
impairment that persists for a duration of at least 2 weeks.
It further requires that the person should never have met
the criteria of any other depressive or bipolar disorder,
does not currently meet active or residual criteria for any
psychotic disorders and as well as does not meet the criteria
for mixed anxiety and depressive disorder.
DSM-5 has a separate category for the depressive disorder
due to another medical condition and describes it as
medical disorder with depressive features (i.e., full criteria
of MDD is not met), major depressive like and mixed-mood
features.
Many elderly patients also present with late-onset dysthymia.
Patients with late onset dysthymia are considered to differ
from those with young onset dysthymia, in terms of absence
of personality disorders and if present, these consist of
obsessive–compulsive personality disorder and avoidant
personality disorder. There is some evidence to suggest that
clinical features of dysthymia in elderly differ from young
onset in terms of higher prevalence of comorbid medical
illness, presence of cognitive deterioration, and presence
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Table-1: Spectrum of Depressive Disorders in Elderly
Classification of Geriatric depressive disorders
According to Symptomatology
• Major Depressive Disorder
• Minor depressive disorder (Other specified depressive disorder,
depressive episode with insufficient symptoms in DSM-5)/ Subsyndromal
or subthreshold depression/ Depression without sadness
• Mixed anxiety-depressive disorder
• Dysthymic disorder
• Bereavement
• Adjustment disorder with depressed mood
According to Associated Etiology
• Mood disorder caused by a general medical Condition (Depressive
disorder due to another medical condition)
• Vascular depression/Depression–executive dysfunction syndrome
• Substance- or medication-induced Depression
of frequent adverse life events and fewer “depressive
cognitions” symptoms but similar neurovegetative and
other somatic symptoms.
ASSESSMENT AND EVALUATION
A comprehensive assessment of depression in elderly is
of paramount importance to evaluate the risk factors,
comorbidity and associated etiological factors, severity
of depression, risk of self-harm and level of dysfunction.
Additionally, assessment also involves establishing a good
therapeutic alliance, deciding about treatment setting and
patient’s safety. It is important to remember that assessment
is a continuous process and patient should be assessed
regularly, as per the need and phase of the treatment.
Comprehensive assessment requires elicitation of detailed
history including assessment for presence of physical
comorbidity, physical examination and mental state
examination. All efforts must be made to collect the history
from multiple sources, especially from the family members.
The complete psychiatric evaluation involves reviewing
history of the present episode and current symptoms, a
psychiatric history including evaluation of symptoms of mania
to rule out bipolar disorder, evaluation of treatment history
in terms of current treatments and responses to previous
treatments,history of medical illnesses, history of substance use
disorders, personal history (e.g., psychological development,
response to life transitions, and major life events), psychosocial
history, review of current medications, thorough physical
examination with review of all the systems, mental status
examination and diagnostic tests as indicated (Table-2).
While assessing elderly for depression, it is important to
remember that elderly patients often under-report their
depressive symptoms and they may not acknowledge being
sad, down or depressed. Common depressive symptoms
(such as lack of enjoyment in normal activities, loss of
interest in life, apprehension about future, poor sleep,
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Table-2: Components of assessment and evaluation
Basic assessments
1. Thorough history with information obtained from all collateral resources
2. Evaluate the association, relationship with physical illnesses
3. Establish and maintain therapeutic alliance
4. Treatment history: type of antidepressants used, response rate,
compliance, side effects/tolerability
5. Medications for other physical illnesses: review the prescription of
the patients for type of medications, their possible interaction with the
proposed antidepressants
6. Differential diagnosis by ruling out secondary depression
7. Detailed psychosocial evaluation: loneliness, poor social/family support,
isolation/no social interaction, dependency, lack of family care and
affection/lack of caregivers, insufficient time spent with children,
stressful life events, perceived poor health status, lifestyle and dietary
factors, lack of hobby, irregular dietary habits, substance use/smoking,
lower spirituality and emotion-based coping
8. Rule out bipolar disorder
9. Physical examination- look for thyroid swelling, evidence for
malnutrition or any specific nutritional deficiency, any other underlying
physical illness
10. Measure blood pressure, pulse, weight and body mass index and waist
circumference, if indicated
11. Mental state examination with special attention to cognitive functions,
pseudodementia
12. Establish diagnosis according to current diagnostic criteria
13. Assess the severity, specifier, subtype of depression
14. Areas to be evaluated: symptom-severity, symptom-dimensions
(psychotic, catatonic , melancholic, cognitive), comorbid physical,
psychiatric and substance use conditions
15. Evaluate the relationship of depression with cognitive symptoms,
diagnosis of depression in presence of dementia
16. Evaluate the risk of suicide and safety issues
17. Evaluate the level of functioning and socio-cultural milieu of the
patient
18. Basic investigations: haemogram, blood sugar, lipid levels,
liver function tests, renal function test, thyroid function test,
electrocardiogram (ECG), serum electrolytes, serum B12 and folic acid
levels (if indicated)
19. Neuroimaging : first-episode of depression seen in late or very late
age; those having neurological signs, or having treatment resistant
depression
20. Determine about the treatment setting
21. Assessments of caregivers: knowledge and understanding about the
disorder, attitudes and beliefs in terms of treatment, impact of the
illness on them and family, personal and social resources
22. Ongoing assessments: response to treatment, side effects, treatment and
medication adherence, the impact of patient’s immediate environment,
disability, other health-care needs, ease of access to and relationship
with the treatment team
Additional/Optional assessments
1. Use of standardized rating scales to rate all assess severity of depression,
activities of daily living, cognitive functions
recurrent thoughts of death, persistent unexplained
pain, poor concentration or impaired memory) are often
misattributed to old age, dementia or poor health. Due
to this depression among elderly is often under-detected
and untreated for a long time. Many elderly patients with
depression often tend to report more somatic and cognitive
symptoms than affective symptoms. It has been reported
that women more often report mood-related symptoms
when compared to men. Patients who do not acknowledge
having depressed mood may report a lack of feeling or
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Avasthi and Grover: Management of Depression in Elderly
emotion or acknowledge a loss of interest and pleasure
in activities. In view of the reporting of fewer depressive
symptoms by elderly patients with depression, some of the
authors have suggested the use of the term “depression
without sadness”, which is considered as a variant of
depression, which is specifically seen in primary care
populations and comprises of symptoms of apathy, loss
of interest, fatigue, difficulty sleeping, and other somatic
symptoms, but not sad mood. However, it is unclear whether
“depression without sadness” is an idiopathic depression, a
depression secondary to medical illness, or a non-affective
syndrome related to chronic medical disease.
Other barriers to accurate diagnosis of depression among
elderly include prevalent stigma and confounding effect
of medical co-morbidity. Stigma often prevents effective
health care seeking behavior and the accurate reporting
of symptoms. Medical comorbidity among elderly patients
with depression is a rule rather than an exception.
Psychological stress of having an illness, ensuing functional
disability, and life changes necessitated by chronic illness
may precipitate depression in susceptible individuals. Many
physical illnesses have been shown to have high prevalence
of depression (Table-3). Accordingly, any elderly individual
presenting with first episode depression in the late age
must be properly evaluated for underlying physical illnesses.
There is significant overlap of symptoms of depression
and various medical illnesses and it is often difficult to
segregate the attribution of symptoms. Symptoms such as
weight loss, fatigue and insomnia may overlap with patients
suffering from various physical illnesses. At times, evolution
of depression may be indicated by appearance of new onset
somatic symptoms, when the physical health was static.
Efforts must be made to evaluate anhedonia and depressive
ideations like self-deprecation, guilt, etc. The diagnosis of
“depression due to a general medical condition” can be
used for medical illnesses with a known etiologic link to
depression. However, some of the authors consider this
terminology to be irrelevant to significant proportion of the
elderly patients in whom overall medical burden contributes
to their depression. Various approaches have been used
for diagnosing depression in medically ill subjects. These
include exclusive approach, substitutive approach, best
estimate approach and inclusive approach. The “exclusive
approach” does not consider neurovegetative symptoms
(e.g., changes in sleep, energy, appetite, and weight) to
make a diagnosis of depression, whereas the “substitutive
approach”, replaces the neurovegetative symptoms
included in the nosological system by non-somatic cognitive
symptoms (e.g., hopelessness) when defining a major
depressive episode (MDD). The “best estimate approach”
involves use of clinical judgment to consider whether the
symptom is caused by a physical disorder or is part of a
depressive syndrome. The “inclusive approach” presumes
that all the symptoms contribute to the depressive episode,
irrespective of the cause. In general it is suggested that,
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Avasthi and Grover: Management of Depression in Elderly
to overcome the under-recognition of depressive disorders
among elderly, an inclusive approach to diagnosis may be
preferable in older medically ill patients. However, it is also
important to consider all the contributing factors towards
the depressive symptoms (e.g., medical causes) to avoid use
of unnecessary medications.
In terms of physical illnesses, it is important to remember
that depression among elderly is often associated with
presence of hypertension and accordingly vascular risk
factors have received considerable attention in the
research. This is known as “vascular depression” and
newer studies based on magnetic resonance imaging
(MRI) suggest that vascular depression accounts for
upto 50% of depression in elderly. Patients with vascular
depression are considered to have a distinct clinical and
neuropsychological profile, which is linked to the presence
of hypertension. The MRI findings in such patients include
loss of brain volume and loss of white matter integrity.
In general vascular depression has been shown to be
associated with poor treatment outcomes, higher risk
of development of cognitive impairments. Relationship
of vascular depression with development of Alzheimer’s
disease is non-conclusive, with some reports suggesting
that these patients have higher risk of progressing to
Alzheimer’s disease. A review provided the updated
information on features of vascular depression and this
include: onset of depression at ≥ 65 years of age, absence
of family history of depression, presence of executive
dysfunctions, loss of energy, subjective feeling of sadness,
anhedonia, psychomotor retardation, motivational
Table-3: Some of the physical illnesses commonly
associated with depression
1. Acquired immunodeficiency syndrome (AIDS)
2. Addison’s disease
3. Alzheimer’s Disease
4. Cancers: pancreas, lungs, oral cavity
5. Cerebral atherosclerosis, infarction
6. Coronary Artery Disease
7. Cushing’s Syndrome
8. Degenerative Brain Disease
9. Diabetes mellitus
10. Electrolyte imbalance (e.g., hypernatremia, hypercalcemia,
hypokalemia, hyperkalemia)
11. Epilepsy (temporal lobe epilepsy)
12. Hyperparathyroidism
13. Hyperthyroidism
14. Hypothyroidism
15. Intracranial tumors
16. Multiple Sclerosis
17. Myocardial infarction
18. Nutritional deficiencies: B12, folic acid, thiamine
19. Parkinson’s Disease
20. Porphyria
21. Post stroke
22. Renal Disease: Chronic kidney disease (CKD), patients undergoing
dialysis
23. Rheumatoid arthritis
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problems, reduced processing speed and visuospatial
skills, deficits in self initiation and lack of insight; and may
not meet the criteria for any mood disorder as per the
DSM-5, presence of high cardiac illness burden, presence
of increased rates of vascular risk factors (hypertension,
etc.), fluctuating course of cognitive impairment due to
progression of white matter hyperintensities, greater
treatment resistance and poorer outcome, higher risk for
cognitive decline and association with increased mortality
(Table-4). However, it is important to remember that
DSM-5 has not incorporated this entity in its classificatory
system. Another entity related to vascular depression is
depression-dysexecutive syndrome (DES) which is seen in
patients with vascular risk factors and is associated with
executive dysfunction due to dysfunction in the frontal-
subcortical circuit.
Depression is elderly is also often associated with use of
certain medications (Table-5). Accordingly obtaining a
detailed treatment history is of paramount importance.
The treatment history may not be limited only to the
prescription drugs, but should extend to evaluation of over
the counter drugs and use of medicines from alternative
schools of medicine. It is important to evaluate the temporal
correlation of use of medications (starting of medications,
escalation of dose of medication) and emergence of
depressive symptoms to make any conclusion about the
association. However, it is important to note that except
for few drugs (e.g. corticosteroids, interferon), evidence for
risk of development of depression with specific medications
is inadequate and perhaps overstated.
While assessing depression among elderly it is important to
remember that many elderly have atypical presentation of
their depression. They may present with chronic unexplained
physical symptoms, cognitive symptoms, change in
behaviour, anxiety and worries, irritability and dysphoria, etc.
However, development of a therapeutic alliance and proper
assessment often reveals presence of depressive symptoms
in these patients. While evaluating elderly patients, it
must be remembered that when neurotic symptoms like
Table-4: Features of Vascular Depression in Elderly
• First episode of depression after the age of 65 years
• Symptomatology: subjective feeling of sadness, loss of energy,
anhedonia, psychomotor retardation, cognitive symptoms (executive
dysfunctions, reduced processing speed and visuospatial skills),
problems with level of motivation, poor self-initiative, lack of insight
• Depressive symptoms may not meet criteria for any mood disorder as per
DSM-5
• Lack of family history of depression
• Presence of cardiac morbidity, hypertension, and other vascular risk
factors
• Higher risk for cognitive decline and progression to dementia
• Fluctuations in the cognitive functions which may be related to white
matter hyperintensities
• Poor response to treatment and higher mortality
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Avasthi and Grover: Management of Depression in Elderly

Table-5: Medications known to cause depression has means to suicide then a judgment may be made
Cardiovascular drugs Anti-infective agents Sedatives and concerning the lethality of those means. Family history of
• ACE inhibitors • Ampicillin antianxiety suicide also must be inquired into and taken into account
• Calcium channel blockers • Chloramphenicol drugs while assessing the risk of future self-harm. Patients found
• Clonidine • Chloroquine • Barbiturates to have suicidal or homicidal ideation, intention or plans
• Digitalis • Clofazimine • Benzodiazepines
• Guanethidine • Cycloserine • Chloral hydrate
need to be monitored closely and hospitalization should be
• Hydralazine • Cyclosporine • Ethanol considered for those at high risk of self-harm/suicide.
• Methyldopa • Dapsone Other drugs
• Procainamide • Ethambutol • Choline At times depression among elderly is often confused with
• Propranolol • Ethionamide • Cimetidine dementia. Symptoms like apathy, loss of initiative, social
• Reserpine • Foscarnet • Disulfiram
• Thiazide diuretics • Ganciclovir • Lecithin
withdrawal and cognitive dysfunction (poor attention and
• Guanabenz • Griseofulvin • Methysergide concentration) are present in both the disorders. Compared
• Zolamide diuretics • Isoniazid • Phenylephrine to dementia, depression often have more rapid onset, have
Chemotherapeutics • Interferon • Physostigmine evidence of mood change, diurnal variation with morning
• 6-Azauridine • Metoclopramide • Ranitidine
worsening of symptoms, intact orientation, fluctuating
• Asparaginase • Metronidazole • Statins
• Azathioprine • Nalidixic acid • Tamoxifen and inconsistent cognitive deficits, may give more ‘don’t
• Bleomycin • Nitrofurantoin Antiretroviral drugs know’ answers, significant personal distress, disturbed
• Cisplatin • Penicillin G procaine • Atazanavir sleep and appetite and suicidal ideations. However, it is
• Cyclophosphamide • Streptomycin • Efavirenz important to remember that many patients with dementia
• Doxorubicin • Sulfonamides • Enfuvirtide
also develop depression and it is often missed in such a
• Vinblastine • Tetracycline • Saquinavir
• Vincristine • Trimethoprim • Zidovudine scenario. Certain symptoms like psychomotor slowing,
Antiparkinsonian drugs Hormones Anticonvulsants emotional lability, crying spells, insomnia, weight loss,
• Amantadine • Adrenocorticotropin • Ethosuximide inability to verbalize affective state and pessimism are
• Bromocriptine • Anabolic steroids • Phenobarbital seen in both depressed and non-depressed patients with
• Levodopa • Glucocorticoids • Phenytoin
dementia. Some of the studies suggest that patient’s with
Stimulants • Oral contraceptives • Primidone
• Amphetamines Antipsychotic drugs • Tiagabine Alzheimer’s disease with depression display more self-pity,
withdrawal) • Fluphenazine • Vigabatrin rejection sensitivity, anhedonia and fewer neurovegetative
• Caffeine • Haloperidol Anti-inflammatory signs than non-demented depressed older patients. Specific
• Cocaine (withdrawal) agents scales like Cornell Scale for depression in dementia, which is
• Methylphenidate (Ritalin) • NSAIDS
considered to be the gold standard for assessing depressive
symptoms among patients with dementia, may be used.
hypochondriasis, obsessive compulsive features emerge for Combining data from the patient interview, information
the first time in life in old age, than more often than not, obtained by caregivers and use of specific scale have been
these are associated with depression. Accordingly, in all such suggested to provide a reliable and valid assessment. The
cases, depression must be ruled out properly. Elderly patients National Institute of Mental Health has developed criteria
presenting with depression should also be properly evaluated for diagnosis of depression in patients with Alzheimer’s
for substance use disorders. At times, elderly patients with dementia. This includes a list of 10 symptoms, out of
depression may present with alcohol dependence arising for which 3 or more must be present during the same 2 week
the first time in the later life. A thorough history from the period and represent a change from previous functioning.
patient and an informant often provides clarity. Whenever Out of the 3 criteria fulfilled, at least one of these must be
required, appropriate tests like, urine or blood screens depressed mood or decreased positive affect or pleasure.
(with prior consent) may be used to confirm the existence of Other features of the criteria include social isolation or
comorbid substance abuse/dependence. withdrawal, disruption in appetite which is not related to
another medical condition, disruption in sleep, psychomotor
Elderly patients with depression are at higher risk for self- changes (agitation or slowed behavior), irritability, fatigue
harm and completed suicide when compared to young or loss of energy, feelings of worthlessness or hopelessness,
adults. Depression is the most common risk factor for or inappropriate or excessive guilt and recurrent thoughts of
suicide in elderly. Hence, every patient must be properly death, suicide plans or a suicide attempt. These symptoms
evaluated for suicidal behaviours. The risk factor for suicide must be present for at least 2 weeks for considering the
among elderly and those with depression include older age, diagnosis of depression among patients with definite
male gender, severe anxiety, panic attacks, living alone, diagnosis of Alzheimer’s disease as per the DSM-IV criteria.
severe depression, bereavement (especially in men) and The symptoms must be associated with clinically significant
presence of comorbid alcohol misuse, physical pain and distress or disruption in function; symptoms are not part of
history of suicide attempts in the past. Clinicians should delirium, are not related to physiological effect of substance
directly enquire about the presence of suicidal ideations, and are not accounted by other psychiatric conditions
planning and availability of means of suicide. If the patient (Table-6).

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Avasthi and Grover: Management of Depression in Elderly
Table-6: NIMH Provisional Diagnostic Criteria for
Depression in Alzheimer Disease
A. Three (or more) of the following symptoms must be present during the
same 2-week period and represent a change from previous functioning.
At least one of the symptoms must either be 1) depressed mood or 2)
decreased positive affect or pleasure
1. Clinically significant depressed mood
2. Decreased positive affect or pleasure in response to social contacts and
usual activities
3. Social isolation or withdrawal
4. Disruption in appetite
5. Disruption in sleep
6. Psychomotor changes
7. Irritability
8. Fatigue or loss of energy
9. Feelings of worthlessness, hopelessness, or excessive or inappropriate
guilt
10. Recurrent thoughts of death, suicidal ideation, plan or attempt
B. All criteria are met for Dementia of the Alzheimer Type (DSM-IV)
C. The symptoms cause clinically significant distress or disruption in
functioning
D. The symptoms do not occur exclusively in the course of delirium
E. The symptoms are not due to the direct physiological effects of a
substance
F. The symptoms are not better accounted for by other conditions such as
major depressive disorder, bipolar disorder, bereavement, schizophrenia,
schizoaffective disorder, psychosis of Alzheimer disease, anxiety
disorders, or substance-related disorders
An important aspect for evaluation of depression in elderly
also involves evaluation for nutritional deficiencies which
may be responsible for the depressive symptoms and
correction of these may be sufficient to manage depressive
symptoms.
Due attention must be given to psychosocial factors which
may be associated with onset, continuation/maintenance
of depression among elderly. Various psychosocial
factors associated with depression among elderly include
loneliness, poor social/family support, isolation/no social
interaction, dependency, lack of family care and affection/
lack of caregivers, insufficient time spent with children,
stressful life events, perceived poor health status, lifestyle
and dietary factors, lack of hobby, irregular dietary habits,
substance use/smoking, lower spirituality and emotion-
based coping.
Before considering the diagnosis of unipolar depressive
disorders, it is important to ascertain that patient does
not have bipolar disorder as use of antidepressants in
patients with bipolar disorder can lead to antidepressant
induced switch. Elderly patients presenting with depressive
disorders often do not come up with history of previous
hypomanic or manic episodes. Meticulous history from the
patient, family members, review of treatment records often
provide important clues and aid in confirming the diagnosis
of bipolar disorder. At times use of standardized scales
like mood disorder questionnaire can help in detecting
bipolarity. Some of the clinical features which should alert
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a clinician about the possibility of bipolar disorder include
presence of psychotic features, marked psychomotor
retardation, reverse neurovegetative symptoms (excessive
sleep and appetite), irritability of mood, anger and family
history of bipolar disorder.
Evaluation of history should also take the longitudinal
life course perspective to evaluate for previous episodes
and presence of symptoms of depression amounting to
dysthymia. History taking should look at the relationship of
onset of depression with change in season (seasonal affective
disorder) and relationship with menopause etc. Response
to previous treatment should also be reviewed and whether
the patient achieved full remission, partial remission and did
not respond to treatment should be evaluated.
Elderly patients are at higher risk of completed suicide
when compared with the young patients.
Depression is associated with marked dysfunction in
the domains of interpersonal relationships, work, living
conditions, activities of daily living, instrumental activities
of daily living, and other medical or health-related needs.
At baseline, these need to be noted and subsequently
monitored. If feasible, standard scales may be used to
record these dysfunctions. The areas of dysfunction must
be addressed by encouraging the patient to set realistic,
attainable goals for themselves in terms of desirable levels
of functioning.
All the elderly subjects with depressive disorders need to be
investigated. The list of investigations is generally guided
by the physical evaluation and history of medical illnesses.
However, it is important to remember that if at all there
is no historical evidence of medical illness and nothing
significant is found in physical examination to warrant
laboratory investigation then also the elderly patients
should be subjected to a minimum battery comprising of
haemogram, liver function tests, renal function tests, urine
analysis, electrocardiography (ECG) and serum electrolytes.
Some authors also advise to consider thyroid function
tests, vitamin B12 and folate levels and serum levels of drugs
received by the patient. Neuroimaging may be considered
in those with in late or very late onset first episode
depression, those having associated neurological signs and
those experiencing treatment resistant depression.
Besides, obtaining information from the patients and
caregivers, it is also important to evaluate their knowledge
and understanding about the symptoms and the disorder,
their attitudes and beliefs about the symptoms and
treatment, the impact of the illness on them and their
personal and social resources.
Many a times, elderly patients with depression present to the
primary care to the physicians, who may require assistance
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of screening questionnaires to diagnose depression in
elderly. The available questionnaires include Geriatric
Depression Scale (GDS), Evans Liverpool Depression
Rating Scale (ELDRS), Brief Assessment Schedule (BASDEC)
and Patient Health Questionnaire (PHQ-9). However, it is
important to note that these are screening questionnaires/
scales, and detailed interview will be required for
confirming the diagnosis. It also important to remember
that level of cognitive impairment and visual deficits
must be taken into account while asking the patients to
complete these questionnaires or while administrating
these questionnaires. Out of these 3 questionnaires, GDS is
available in Hindi.
Scales can also be used to rate the severity of depression
among elderly. The various scales which can be used include
Figure-1: Initial evaluation and management plan for Depression
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Avasthi and Grover: Management of Depression in Elderly
Hamilton Rating Scale for Depression (HAM-D), Zung Self-
Rating Depression Scale (SDS), Geriatric Depression Scale
(GDS), Beck Depression Inventory (BDI), Montgomery-
Asberg Depression Rating Scale (MADRS) and Cornell Scale
for Depression in Dementia (CSDD). Among the various
scales, GDS is the most well validated scale for use in elderly
with intact cognitive functions.
Formulating a treatment plan
Formulation of treatment plan involves deciding about
treatment setting, medications to be prescribed and
psychological interventions to be used (Figure-1). Wherever
possible, the patients may be involved in preparing the
treatment plan. Caregivers must also be consulted in
formulating a treatment plan. The role of caregivers becomes
more important when the patient is not in a condition to
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Avasthi and Grover: Management of Depression in Elderly
participate in treatment decisions due to severity of the
depression, lack of insight or marked cognitive impairment.
The treatment plan needs to be practical, feasible and
flexible to attend to the needs of the patients and
caregivers. The treatment plan initially formulated need to
be continuously re-evaluated and updated as per the clinical
and psychosocial needs.
DETERMINE A TREATMENT SETTING
Patients with depression can be managed on the outpatient
basis. However, it is recommended that patients be managed
in a setting which is most safe and effective. The decision
about treatment setting must take into account symptom
severity, comorbid physical and psychiatric conditions,
suicidality, homicidal behaviour, level of functioning
and available support system. It should also take into
consideration the ability of a patient to adequately care for
themselves, provide information about the health status to
the clinician and cooperate with treatment. Further, this
should be an ongoing process throughout the course of
treatment. Some of the indications for inpatient care are
given in Table-7.
All inpatients should have accompanying family caregivers.
In case inpatient care facilities are not available, then the
patient and/or family must be informed about such a need
and admission in nearest available inpatient facility can be
facilitated.
ESTABLISH AND MAINTAIN A THERAPEUTIC
ALLIANCE
Irrespective of the use of various treatment modalities, it
is important for the clinicians to establish a therapeutic
alliance with the patient. Depression often runs a chronic
Table-7: Indications for admission in elderly patients
with depression
1. Patients expressing suicidal ideas of a definite sort, or who have made a
suicide attempt
2. Patients threatening to harm themselves for the first time (especially
men)
3. Patients with problems with treatment compliance or delivery, leading
to unduly protracted treatment
4. Patients requiring electroconvulsive therapy (Catatonia)
5. Patients who neglect themselves substantially, particularly their fluid
intake
6. Patients with severe malnutrition, patients refusing to eat which puts the
life of patient at risk
7. Patients requiring removal from a hostile social environment
8. Patients who are in severe distress to the extent that they need
tranquillisation or skilled nursing care
9. Patients with comorbid physical illness(es) that is complicating
treatment and make outpatient treatment unsafe or ineffective
10. Patients who have not responded adequately to outpatient treatment
11. Frail elderly
12. Lack of adequate social support
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course and requires patients to actively participate and
adhere to treatment for long periods. Another important
aspect of successful treatment is tolerating the side effects
of various treatment modalities. For these reasons, a strong
treatment alliance is crucial. For clinicians, it is important to
understand that paying attention to the concerns of patients
and their families as well as their wishes for treatment
enhances the therapeutic alliance.
MONITOR THE PATIENT’S PSYCHIATRIC
STATUS AND SAFETY
Management of depression is an ongoing process, which
requires continuous assessment of course of symptoms and
acceptability of treatment. Accordingly, it is important to
be on surveillance for emergence of destructive impulses
towards self or others and hospitalization or more intensive
treatment need to be considered for patients at higher risk.
At times, patients may present with significant changes in
psychiatric status or emergence of new symptoms, which
may warrant a diagnostic re-evaluation of the patient.
PROVIDE EDUCATION TO THE PATIENT AND,
WHEN APPROPRIATE, TO THE FAMILY
All patients and their caregivers need to be educated about
symptoms of depression, available treatment modality,
course of disorder and time to response to treatment.
Specific educational elements may be helpful in some
circumstances, e.g. that depression is a real illness and that
effective treatments are both necessary and available may
be crucial for patients who attribute their illness to a moral
defect, witch craft or harbour other supernatural causation
for their depressive disorder. Education regarding available
treatment options will help patients make informed
decisions, anticipate side effects and adhere to treatments.
Another important aspect of providing education is
informing the patient and especially family about the lag
period of onset of action of antidepressants.
ENHANCE TREATMENT ADHERENCE
Adequate management of depression requires adherence to
treatment plans. Many elderly patients may attach stigma
to depression and disagree with clinicians when informed
about their diagnosis. Patients also often fear of becoming
addicted to antidepressants and the impact of psychotropics
on their medical disorders. Sometimes, patients who are
overtly symptomatic may be poorly motivated and unduly
pessimistic about their chances of improvement with
treatment. On the other hand, many patients, who achieve
clinical remission with treatment may underestimate the
need for continued treatment and consider it as a burden.
Some patients may not be able to take care of themselves
due to cognitive deficits. Side effects are also well known to
contribute to treatment non-adherence.
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Accordingly, treatment adherence can be improved by
informing the patients about when and how often to take
medicine, lag period of onset of action (at least 3-4 weeks
will be required for the beneficial effects to emerge), the
need to take medication even after feeling better, the need
to consultation prior to discontinuing medication, what is
to be done in the face of side effects and what is to be
done, in case of a problem. Medication adherence among
elderly can also be improved by simplifying the treatment
regimen and reducing the cost of treatment. If the patient
has severe, persistent or recurrent non-adherence with
treatment, than there may be a need to evaluate the
psychological conflicts or psychopathology which may be
contributing to the non-adherence. Appropriate measures
must be taken to address these issues. Family members
must be involved in all stages of treatment and all form
of psychoeducation, as they can play an important role in
enhancing treatment adherence.
ADDRESS THE ISSUE OF EARLY SIGNS OF
RELAPSE
Patient and family members need to be informed about
the chances of relapse after improvement. Information
need to be provided in terms of recognising early signs and
symptoms of new episodes, need for seeking treatment at
the earliest to reduce the chance of development of full-
blown relapse.
TREATMENT OPTIONS FOR MANAGEMENT
FOR DEPRESSION
The available treatment options for management of
depression can be broadly categorised into antidepressants,
somatic treatments and psychosocial interventions. The
various somatic treatments include electro-convulsive
therapy (ECT) repetitive transcranial magnetic stimulation
(rTMS), transcranial direct stimulation, vagal nerve
stimulation and deep brain stimulation. Other some of the less
commonly recommended treatments include light therapy
and sleep deprivation. Besides these, benzodiazepines are
often prescribed as adjunctive treatment during the initial
phase of treatment. Patients who do not respond to the
first line treatments may require use of lithium and thyroid
supplements as augmenting agents.
Depression can be managed with a whole range of
antidepressant medications (Table-8). Antidepressants
are the usually preferred modality of treatment
for mild, moderate, or severe depressive episode.
Psychotherapeutic treatments are usually indicated for
management of patients with minor depression and mild
to moderate major depression. Clinical features that may
guide the choice of use of psychotherapeutic treatments
include the presence of significant psychosocial stressors,
intrapsychic conflict, interpersonal difficulties, or axis II
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Avasthi and Grover: Management of Depression in Elderly
comorbidity. Many times, patients themselves may be
averse to use of antidepressants and express desire for
psychotherapeutic treatments as the initial treatment
modality. In such a scenario, patient’s preference
must be respected. Combination of antidepressants
and psychotherapeutic interventions may be useful
initial treatment choice for patients with psychosocial
stressors, intrapsychic conflict, interpersonal problems,
or a comorbid axis II disorder together with moderate
to severe major depressive disorder. Other indications
for combined treatment with antidepressants and
psychotherapy include partial response to adequate trials
of antidepressants or psychotherapeutic interventions and
patients who are poorly adherent to pharmacotherapy.
Presence of psychotic symptoms may suggest combined
use of antidepressant and antipsychotic medications
or ECT. Other indications for ECT include presence of
catatonic features not responding to benzodiazepines
(e.g. lorazepam), high risk of suicidality, presence of
comorbid general medical conditions precluding the use
of antidepressant medications, patients refusing food
and are nutritionally compromised and those who have
a past history of positive response to ECT. The patient
preference is another important consideration that
may influence the decision to select ECT as a treatment
modality. However, it is to be remembered that ECT
is relatively contraindicated in patients with recent
myocardial infarction, brain tumor, cerebral aneurysm,
and uncontrolled heart failure.
Selecting specific antidepressant: In general, there is no
difference in the efficacy of various antidepressants in
management of depression. A metanalysis, which included
51 randomised controlled trials (RCTs) comparing various
antidepressants medications showed lack of significant
difference in the efficacy of various antidepressant classes.
Studies which have compared various antidepressants
head-to-head show that there is lack of difference in
the efficacy of escitalopram, citalopram, sertraline and
paroxetine. Another meta-regression analysis, which
included 34 RCTs showed lower response rate to various
antidepressants in patients of male gender, older age and
those having longer duration of current episode. Better
response rate was seen in patients with higher baseline
severity of depression and those experiencing first episode
of depression.
Hence selection of antidepressant is guided by other
features which can be broadly divided into patient
specific and drug specific factors. The patient specific
factors include patient preference, past history of
response/ tolerability to medication, family history
of response to a particular antidepressant, comorbid
medical illness, comorbid psychiatric disorder/
symptoms, other medication being taken and intellectual
and psychological capacities. The drug specific factors
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Avasthi and Grover: Management of Depression in Elderly

Table-8: Antidepressants Armamentarium cost, dosing schedule, type of formulations available

Antidepressant Usual Average Maximum Side effects and safety in overdose. Elderly people are generally
Starting dose in recommended more susceptible to anticholinergic effects, and the
dose in mg/day dose (mg/day) newer antidepressants should therefore be preferred.
mg/day If a tricyclic antidepressant has to be used, drugs with
Selective serotonin reuptake inhibitors (SSRI) pronounced anticholinergic effects, such as amitriptyline,
Fluoxetine 10 20 20 GI distress,
Paroxetine 10-20 20-30 30-40 weight loss/gain,
should be avoided. Antidepressants associated with side
Fluvoxamine 50 50-200 200 anxiety, insomnia, effects like hypotension, and those with highly sedating
Sertraline 25 50-150 200 hyponatremia, Sexual properties must be avoided.
Citalopram 10 20-40 20 if (age>65); dysfunction,
Escitalopram 5 10-20 40 (age <65
yrs)
Among the cyclic compounds, desipramine is less sedating
10 if (age>65); and can be taken during the day, and nortriptyline is less
40 (age <65 likely to cause orthostatic hypotension than amitriptyline
yrs) or imipramine. Although MAOIs are thought to be
Serotonin Norepinephrine reuptake Inhibitors (NSRI)
Venlafaxine 37.5 75-225 300 GI distress,
dangerous and difficult to use, drugs such as phenelzine are
Duloxetine 20 30-60 60 may increase relatively safe and effective in older patients. However, it is
Levomilnacipran 20 40-120 120 blood pressure important to remember that MAO inhibitors are associated
25 50 100 (venlafaxine), Mild with development of hypotension, hypertension, and food-
Desvenlafaxine anti-cholinergics
effects, drowsiness, drug interactions. Moclobemide is well tolerated by older
conduction people. Although a special diet is not required, patients
abnormalities, should be aware of the drug interactions with painkillers
Noradrenaline and Specific Serotonin Antidepressants (NaSSA) and other antidepressants. Blood pressure monitoring is
Mirtazapine 7.5 15-30 30-45 GI distress, Risk
of sedation, weight
necessary with venlafaxine in patients with pre-existing
gain, orthostatic cardiovascular disease and patients taking relatively high
hypotension dosages. Nefazodone works well in patients with anxiety
Unicyclic and depression. Gastrointestinal symptoms side effects
Bupropion SR 100 200 300 Risk of seizures
with SSRIs are well known. Among the SSRIs sertraline and
Tricyclic Secondary Amines
Desimipramine 10-25 50-150 300 Anticholinergic citalopram have the least potential for drug interactions.
Nortrptyline 10-25 40-75 200 properties; For clinicians it is important to remember that the
cardiovascular side antidepressant effect may be more delayed in elderly people
effects
than in younger subjects, and treatment may need to be
Tricyclic tertiary amines (TCAs)
Amitriptyline 10-25 25-150 150 Anticholinergic continued for longer than six months. A small proportion
Doxepin 10-25 25-75 150 effects, drowsiness, of elderly patients who are prescribed antidepressants may
Imipramine 10-25 50-150 150 orthostasis, go on to develop hyponatremia. Hyponatremia is usually
Clomipramine 10-25 50-150 150 conduction seen during the initial phase of treament. The various risk
abnormalities,
mild GI distress, factors for development of hyponatremia include older age,
weight gain, Sexual female gender, low body weight, presence of comorbid
dysfunction, physical illnesses (i.e., diabetes mellitus, hypertension,
Atypical antidepressants/Serotonin Modulators hypothyroidism, chronic obstructive pulmonary disease,
Trazadone 25 50-150 150 GI distress, Mild
Nefazodone 25 50-150 150 anticholinergic cardiac failure, head Injury, stroke, cirrhosis of liver
effects, drowsiness, and presence of malignancies), concomitant use of
orthostasis, other medications (i.e., diuretics, antihypertensives,
conduction antidepressants, cytochrome P450 inhibitors), past history
abnormalities,
weight gain, severe of hyponatremia, low baseline serum sodium levels,
hepatotoxicity summer season and initial phase of antidepressant therapy.
Reversible Selective Mono Amine Oxidase Inhibitors (RIMA) Accordingly, some of the authors suggest evaluating the
Moclobemide 100 150-200 300 Decreased appetite, baseline serum sodium levels in all elderly patients prior
increase in suicidal
behaviours, agitation, to initiation of antidepressants and monitoring the same
hyponatremia during the initial phase of treatment. Other rare but life-
Serotonin partial agonist reuptake inhibitor (SPARI) threatening side effects of antidepressants include upper
Vilazodone 10 10-20 20-40 Diarrhea, nausea gastro-intestinal (GI) bleeding. It is in general suggested
or vomiting, and
insomnia to be more common in elderly compared to young adult
patients. Antidepressants, specifically those which act
on serotonergic system, decrease platelet aggregation
include the anticipated side effects, the safety or and increase the risk of bleeding. Risk of serotonergic
tolerability of these side effects for individual patients, antidepressants associated GI bleed is high in elderly,

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those with history of peptic ulcers, gastritis, oesophageal medications (i.e., corticosteroids, warfarin, clopidogrel,
varices, gastric or colorectal cancers, chronic alcohol use, aspirin and other non-steroidal anti-inflammatory agents,
liver disease, coagulopathies and concomitant use of other calcium channel blockers, concomitant use of more than one
antidepressant). Accordingly, if required antidepressants
Table-9: Monitor or avoid following combinations in are to be used, these must be used under the cover of
elderly proton pump blockers, to reduce the risk of GI bleeding.
Agent Absolutely Avoid if Carefully monitor Possibility of drug interactions must always be kept in mind
contraindicated possible while selecting an antidepressant and certain combinations
TCAs MAOIs, other Inhibitors Antihypertensive must be avoided (Table-9). The most clinically significant
TCAs of CyP-450 (egguanethidine), drug interactions usually involve inhibition or induction of
anticholinergic Thyroid drugs, Sedatives/ CYP450 enzymes. Accordingly, the clinicians can use ready
agents hypnotics
reckoner or online drug interaction calculators to evaluate
Sympathomimetic drugs
(e.g., epinephrine) for the possible drug interactions.
Fluoxetine MAOIs TCAs, Warfarin, Haloperidol,
Phenytoin, Clozapine In general, SSRIs are considered to be the first line
Cisapride, alprazolam, triazolam, antidepressants because of the side effect and safety
codeine, carbamazepine
Flecainide, beta blockers,
profile. Other alternatives include tricyclic antidepressants,
propafenone cyclobenzaprine, mirtazapine, bupropion, and venlafaxine.
lithium, serotonergic
drugs (eg tryptophan Institution of antidepressant therapy: While using
dextromethorphan) antidepressants among elderly, it is important to take
Sertraline MAOIs Codeine TCAs, haloperidol,
Cisapride warfarin ,cimetidine,
age related pharmacokinetic and pharmacodynamic
diazepam, tolbutamide changes into consideration (Table-10). Accordingly, it is
,lithium suggested that antidepressants must be started in lower
serotonergic drugs doses and the general principle of “start low and go
Paroxetine MAOIs TCAs, codeine, Haloperidol, Warfarin, slow” need to be followed. Usually the medication must
flecainide, lithium, digoxin,
propafenone procyclidine,
be started in the lower doses and the doses must be
phenobarbital, cimetidine titrated upwards, depending on the response and the side
theophylline, phenytoin effects experienced. Patients started on antidepressants
,serotonergic drugs need to be monitored carefully to assess the response
Citalopram MAOIs TCAs, metoprolol to pharmacotherapy as well as the emergence of side
,cimetidine
lithium,serotonergic drugs
effects and safety. Factors which influence the frequency
Fluvoxamine MAOIs TCAs, Warfarin, alprazolam, of monitoring include severity of illness, patient’s co-
cisapride Clozapine midazolam, operation with treatment, the availability of social support
haloperidol, triazolam, theophylline, and the presence of comorbid general medical problems.
diazepam lithium The dose of antidepressants can be titrated to the full
serotonergic drugs
Bupropion MAOIs All agents Levodopa
therapeutic doses over the initial weeks of treatment, but
that lower it is usually guided by the development of side effects and
the seizure the presence of comorbid conditions. Patients need to be
threshold (eg monitored closely for response to pharmacotherapy as well
antipsychotics as the emergence of side effects, clinical condition, and
antidepressants
theophylline
safety. Visits should be frequent enough to monitor and
systemic address suicidality and to promote treatment adherence.
steroids) The frequency of monitoring during the acute phase of
Venlafaxine MAOIs Norepinephrine Cimetidine, serotonergic pharmacotherapy can vary from once a week in routine
agonists (when agents cases to multiple times per week in more complex cases.
high doses of
venlafaxine are
Clinicians should also reassure patients that they may feel
prescribed) worse before they start to feel better.
Nefazodone MAOIs Desipramine, Digoxin, haloperidol,
cisapride alprazolam, propranolol, serotonergic The dose of antidepressants can be increased if patient
triazolam agents compliance is good and there is no response during the
Mirtazapine MAOIs Diazepam Serotonergic drugs,
antihistamines
initial 3 weeks of treatment. If partial response to treatment
alpha1-adrenergic is noted that, clinician can wait for another 2 weeks before
antagonists escalating the dose. Improvement with pharmacotherapy
(egdoxazosinmesylate) , can be observed after 4-6 weeks of treatment. If at least
alcohol
a moderate improvement is not observed in 4-6 weeks,

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Avasthi and Grover: Management of Depression in Elderly
reappraisal and adjustment of the pharmacotherapy should
be considered.
Although there is lack of consensus, but most experts agree
that elderly patients require longer time than young adults
to perceive any improvement and moderate improvement
with pharmacotherapy is seen after 4–8 weeks of treatment,
but 2 to 3 months of therapy are necessary to achieve the
full benefit of treatment. The delayed clinical response to
antidepressants makes it difficult to establish the optimal
dose quickly. The individual dose is usually decided by trial
and error. The patient is usually the last to notice a change,
and others often will tell the person that he/she looks better
than before.
At least 30% of elderly patients with depression do not
respond to first-line treatment with an antidepressant. If
at least moderate improvement is not observed following
4–8 weeks of pharmacotherapy, a thorough review
must be done for re-evaluation of diagnosis, treatment
adherence and pharmacokinetic/pharmacodynamic factors
which may be affecting treatment. Treatment plan must
be revised by implementing one of several therapeutic
options, including maximizing the initial medication
treatment, switching to another antidepressant medication,
augmenting antidepressant medications with other agents,
psychotherapy, or ECT. Maximizing the initial treatment
regimen is perhaps the most conservative strategy. Patients
who show partial response, particularly those with features
of personality disorders, antidepressant medication trial
should be extended as it may allow some patients to
respond more fully. Use of higher antidepressant doses
may be helpful for patients who have received only modest
doses. Patients who have had their dose increased, should
be monitored for an increase in the severity of side effects
or emergence of newer side effects.
Switching to a different antidepressant medication is
a common strategy for treatment-refractory patients,
especially those who have not shown at least partial
response to the initial medication regimen. There is no
consensus about switching and patients can be switched to
an antidepressant medication from the same pharmacologic
class (e.g., from an SSRI to another SSRI) or to one from a
different pharmacologic class (e.g., from an SSRI to a tricyclic
antidepressant). Some expert suggests that while switching,
a drug with a different or broader mechanism of action
should preferably be chosen. While switching to a second
antidepressant, clinicians should remember that there is
some evidence to suggest that venlafaxine may be useful in
patients, who don’t respond to initial pharmacotherapy.
Augmentation of antidepressant may be considered in
patients who show partial response to initial antidepressant
monotherapy. Options include adding a second
antidepressant medication from a different pharmacologic
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class, or adding another adjunctive medication such as
lithium, psychostimulants, modafinil, thyroid hormone,
an anticonvulsant etc. Adding, changing, or increasing
the intensity of psychotherapy should be considered for
patients with MDD who do not respond to medication
treatment. Following any change in treatment, the patient
needs to be closely monitored. If at least moderate level
of improvement is not seen after an additional 4–8 weeks
of treatment, the psychiatrist another thorough review
need to be carried out. This reappraisal should include
verifying the patient’s diagnosis and adherence; uncovering
and addressing clinical factors that may be preventing
improvement, such as the presence of comorbid general
medical conditions or psychiatric conditions (e.g., alcohol
or substance abuse); and uncovering and addressing
psychosocial issues that may be impeding recovery. If no
new information is uncovered to explain the patient’s lack
of adequate response, ECT should be considered.
Psychotherapeutic interventions
Out of the various psychotherapeutic models used in
elderly, cognitive behavior therapy (CBT)/Problem solving
techniques, interpersonal psychotherapy (IPT), Brief
dynamic therapy and reminiscence therapy have been found
to have some evidence (Table-11).Use of psychotherapy is
often guided by the patient preference and the availability
of clinicians with appropriate training and expertise in
specific psychotherapeutic approaches.
Medications plus psychotherapy
As in adults, there is some data to suggest that combination
of pharmacotherapy and psychotherapy is better than
monotherapies in the treatment of late-life depression.
Psychoeducation to the patient and, when appropriate, to
the family
Psychoeducation of patients and family members must be
integral part of all treatment packages. Psychoeducation
need to address the issues of knowledge about the illness,
available treatment options, time to response, side effects
Table-10: Points to remember for prescription of
antidepressants in elderly
1. Elderly are more sensitive to a given drug concentration
2. The body organs of elderly have decreased capacity to adapt
3. Starting dose of an antidepressant must be lower (one third to half) for
elderly compared to the starting dose used in young adults
4. The half-life of most of the antidepressants increase
5. Elderly require longer duration to achieve a steady plasma state
6. Side effects related to dose or concentration will take longer to resolve
7. There is progressive loss of functional body tissues at the cellular level
8. Homeostatic mechanisms that function via central and peripheral
feedback mechanisms are altered in the elderly and make them more
susceptible to side effects
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Table-11: Psychotherapeutic interventions for elderly
patients with depression
Cognitive Behaviour • Helps to change people’s perception of their
Therapy psychosocial environment (cognitive restructuring),
skill building (problem-solving, communication
skills), and mood regulation skills (behavioral
activation)
• Aims to identify maladaptive belief systems, test
the validity of these, and help individuals formulate
more realistic cognitions
• Improvement results from addressing these
cognitions and integration of behavioural
activation/skills to overcome maladaptive
behaviours
• Acceptability and efficacy in this population
Problem solving • This involves teaching the patient to identify
problems, brainstorming for the solutions, deciding
on a solution, implement the solution, and then
evaluation of the same as to whether this is
effective or not  
Interpersonal •  Focuses on the impact of interpersonal
psychotherapy relationships: interpersonal conflict, interpersonal
deficits, role transitions, grief
Reminiscence • Simple/unstructured reminiscence- storytelling of
therapy life events with focus on positive past events
• Structured life review / reminiscence - entire life
span
• Focuses on evaluating positive and negative events
with reframing and integrating these events
• Used with the goal of changing one’s view of
themselves and the events in their life
• Potentially effective treatments for depressive
symptoms in the elderly, effective as other
treatments including pharmacotherapy, alternative
to psycho-/pharmacotherapy
Brief Dynamic •  Aim is to make the subject understand and cope
Therapy better with their conflicts. It focuses on reflections
of past experiences, clarification of affect, the
therapeutic relationship, and the confrontation
of maladaptive interpersonal patterns, wishes or
conflicts.
with medications, need for medication and treatment
adherence, providing information about the course and
outcome, impact of stressors on the course of illness,
improving adaptive coping skills, risk of relapse and
identification of early signs of relapse, address stigma and
encourage maintenance of healthy life style. Important
components of psychoeducation are given in table-12.
ECT in Elderly:
Available data suggests that ECT is as effective in management
of depression in elderly as in adults. Data also suggest that
ECT is well tolerated in patients of old age depression even by
subject aged more than 80 years of age. Studies which have
compared ECT with antidepressants suggest that it is more
effective than antidepressants. Over the years it is increasingly
understood that there is no absolute contraindication for
ECT. The potential risk and benefit should be weighed on
case to case basis and where ever warranted the medical
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Avasthi and Grover: Management of Depression in Elderly
Table-12: Basic components of Psychoeducation
• Assess the knowledge of the patient and caregivers about aetiology,
treatment and prognosis
• Explain about the symptoms and diagnosis of depression
• Evaluate the attitude of the patient and caregivers towards the diagnosis
and treatment
• Clarify the myths associated with diagnosis of depression and
psychotropic medications
• Explain that depression is a medical disorder which is treatable
• Explain about the lag period of onset of action
• Provide information about aetiology
• Provide information about treatment in terms of available options, their
efficacy/effectiveness, side effects, duration of use
• Discuss about importance of medication and treatment compliance
• Provide information about possible course and long term outcome
• Discuss about problems of substance abuse, interpersonal conflict, stress
etc
• Discuss about how to deal with day today stress
• Discuss about communication patterns, problem solving etc
• Enhancing adaptive coping to deal with persistent/residual symptoms
• Discuss about relapse and how to identify the early signs of relapse
• Encourage healthy life styles
• Address issues of stigma
treatment should be optimized before ECT. Data suggests
that the risk of complications in elderly is more among those
receiving more number of medications, especially those
who are on more number of cardiovascular medications.
However, studies have shown that cardiovascular
complications arising during ECT are transient and don’t
prevent successful completion of treatment course. The
commonly reported side effects of ECT include an increased
risk of falls, post-ECT delirium or dementia. Data suggests
that elderly patients with compromised medical status are at
highest risk for prolonged confusion. Occasional study has
also evaluated the effectiveness of ECT in the continuation/
maintenance phase of treatment and this suggests that the
risk of relapse/recurrence with ECT plus nortriptyline is
significantly lower than nortriptyline alone. However, while
using ECT among elderly, certain facts, which can influence
the seizure threshold and seizure duration must be kept
in mind (Table-13). In general, it is important to remember
that seizure threshold increases with age. Elderly patients
also require modifications of doses of anticholinergic,
anesthetic, and relaxant agents in view of the physiological
changes associated with aging. Patients receiving ECT
should be closely monitored for emergence of cognitive side
effects. Patients with pre-existing cognitive deficits are more
vulnerable to the development of cognitive side-effects
during the course of ECT and are at risk of having longer
lasting cognitive side-effects. Cognitive side effects can be
minimized by use of high-dose right unilateral ECT in place
of the bilateral ECT.
Repetitive Transcranial Magnetic Stimulation (rTMS):
rTMS has been used in the management of depression.
It is usually not the first line treatment. Repetitive TMS
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Avasthi and Grover: Management of Depression in Elderly
Table-13: Factors influencing seizure threshold and/ or
seizure duration
Factor Influence
Gender Seizure threshold is higher for men compared to women
Electrode Seizure threshold is higher in bilateral ECT than
placement unilateral ECT
Age Seizure threshold increase as age progresses
Anaesthetic Some anaesthetic agent can raise seizure threshold and/
agents or shorten seizure duration, e.g., barbiturates.
Psychotropic Psychotropic medications like benzodiazepines can raise
drugs seizure threshold and/or shorten seizure duration
Other Caffeine, theophylline, reserpine can decrease seizure
medications threshold
Caffeine, can increase seizure duration
Anticoagulants , β-blockers can raise seizure threshold
ECT ECT itself can raise seizure threshold
Hyperventilation/ Can be used to lengthen seizure duration in people with
hyper- short seizures
oxygenation
applied to the left dorsolateral prefrontal cortex (DLPFC)
has been shown to have beneficial effect. However,
still there is lack of consensus about the exact brain
localization for individual coil placement. RCTs which
have evaluated the role of rTMS in management of
depression in elderly, suggest that rTMS does not have
any beneficial effect at 2 weeks. However, few RCT
reported positive outcome in patients with refractory
depression /treatment resistant depression. Recent
data from RCTs suggest that rTMS is equally effective in
young and older (>60years) patients.
PHASES OF ILLNESS/TREATMENT
Management of depression is divided into three phases, i.e.,
acute phase, continuation phase and maintenance phase.
Maintenance phase of treatment is usually considered when
patient has recurrent depressive disorder (RDD).
ACUTE PHASE TREATMENT
Acute phase treatment must aim to achieve remission.
The various components of acute phase treatment are
shown in Table-14. Selection of initial treatment depends
on severity of depression and patients preferences. The
first and foremost thing for starting treatment is thorough
evaluation (Figure 2 and 3) and deciding about treatment
strategies after considering the severity of the symptoms.
Antidepressant medications may be used as initial
treatment modality for patients with any level of severity
(mild, moderate, or severe). Features that suggest that
medications may be the preferred treatment modality
include history of previous response to antidepressants,
severity of symptoms, presence of marked sleep and
appetite disturbances or agitation, or anticipation of
the need for maintenance therapy. Combination of
antidepressant and antipsychotic medication and/or ECT
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Table-14: Management in the Acute Phase
A. Carrying Comprehensive Assessment of patient (psychiatric/
medical/ psychosocial)
B. Deciding on goals of treatment
1. Achieving remission
2. Ensure safety of patient and others
C. Deciding on the treatment setting
D. Choosing appropriate treatment modality: antidepressants,
psychotherapy, combined treatment with antidepressant and
psychotherapy
E. Use of adjunctive medications when indicated
F. Use of ECT when indicated
G. Psychoeducation
H. Improve social/family support
I. Lifestyle changes
J. Other interventions: exercise, Yoga
may be preferred for patients with severe depression with
psychotic features. Selection of specific antidepressant is
usually guided by the comorbid physical illnesses, possible
side effects, the tolerability of these side effects for
individual patients, patient preference, and concomitant
pharmacotherapy. Usually, SSRIs are considered as the
first line treatment of choice. Among the various SSRIs,
escitalopram and sertraline are considered to have
minimal drug interactions and are considered to be safe
in presence of wide range of physical illnesses. In addition
to the use of antidepressants, depending on the symptom
severity and type of symptoms, such as presence of
insomnia or anxiety, benzodiazepines or other hypnotics
may be used for short duration. When used, these
must be used for shortest possible duration and the
patients and the caregivers must be informed about
the anticipated side effects and risks of over-sedation.
Improvement with pharmacotherapy can be observed
after 4-6 weeks of treatment. Additionally, depending on
the concomitant medications, proton pump blockers may
be used to minimize the GI side effects and to reduce the
risk of GI bleeding. During the initial phase of treatment
serum sodium levels may also be monitored, depending
upon the presence of risk factors. The principle of “start
low and go slow”, must be adhered to and it must be
remembered that elderly usually require lower doses
of antidepressants than the adults. The usual starting
dose which is recommended is half of the adult dose. In
presence of comorbid physical illnesses, the usual starting
dose in an elderly may be one-fourth of the adult dose.
If some improvement (>25%) is not apparent after
continuing antidepressants for 6 weeks, the treatment
should be reviewed and a change of antidepressant needs
to be considered. When patient shows 25-50% improvement
after the initial 4-6 weeks of antidepressant trial, the dose
must be increased to the maximum tolerable dose. If there
is less than 50% improvement with 6-8 weeks of maximum
tolerable dose and the medication compliance is good, a
change in antidepressant may be considered.
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Avasthi and Grover: Management of Depression in Elderly

If moderate improvement is not evident even after 4-8
weeks of pharmacotherapy, then a thorough review with
review of the diagnosis, complicating conditions and
issues, and treatment plan need to be carried out (Figure-4).
Reappraisal of the treatment regimen also includes
evaluation of patient adherence and pharmacokinetic/
pharmacodynamic factors. After the review, the
treatment plan can be redesigned by implementing one
of several therapeutic options, including maximizing
the initial medication treatment, switching to
another antidepressant medication and augmenting
antidepressant medications with other agents/
psychotherapy/ECT. Maximizing the initial treatment
regimen is possibly the most conservative strategy. It is
important to note that, while using the higher therapeutic
doses, it is important to closely monitor the patient for
an increase in the severity of side effects or emergence
of newer side effects.
For treatment-refractory patients, switching to a different
antidepressant medication, especially those who have not
shown at least partial response to the initial medication
regimen is a common strategy. There is lack of consensus
about switching and a patient can be switched to an
antidepressant medication from the same pharmacologic
class (e.g., from an SSRI to another SSRI) or a different
pharmacologic class (e.g., from an SSRI to a tricyclic
antidepressant). In general it is suggested that while
switching, a drug with a different or broader mechanism of
action may be chosen.

Figure -2: Treatment algorithm of mild to moderate Depression in elderly

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Avasthi and Grover: Management of Depression in Elderly
Figure -3: Treatment algorithm of Severe Depression in elderly
Among patients who show partial response to initial
antidepressant monotherapy, augmentation with
another agent may be considered. Augmentation can
be done with a second antidepressant medication from
a different pharmacologic class, or adding agents like
lithium, psychostimulants, modafinil, thyroid hormone, an
anticonvulsant etc. Adding, changing, or increasing the
intensity of psychotherapy may be considered for patients
who do not respond to medication treatment. Close
monitoring of patient need to be done at the time of change
and after the change. If change of treatment strategy do
not yield at least a moderate level of improvement after an
additional 4–8 weeks of treatment, than another thorough
review need to be carried out. This reappraisal may include
reviewing the diagnosis and patient’s medication adherence;
looking for and addressing clinical factors that may be
impeding improvement, such as the presence of comorbid
general medical conditions or psychiatric conditions (e.g.,
alcohol or substance abuse); and identifying and addressing
psychosocial issues that may be preventing recovery. If no
new information emerges which can explain the patient’s
inadequate response, depending on the severity of
depression, ECT may be considered.
Psychotherapeutic interventions: The importance of
psychotherapeutic interventions does not diminish with
increasing age. Available data suggest that in elderly patients
with mild to moderate depression, psychotherapeutic
interventions are as effective as antidepressants. Some
of the studies also suggest that elderly often have better
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treatment compliance, lower dropout rates, and more
positive responses to psychotherapy than younger patients.
Cognitive behavior therapy (CBT) and interpersonal
psychotherapy (IPT) have been found to have sufficient
evidence for management of depression in elderly.
However, it is important to note that studies which have
evaluated the effectiveness of psychotherapy in elderly
with depression have done so in cognitively intact and
medically stable patients and effectiveness outside this
patient group is not fully established. Small studies and
case reports suggest that CBT can be adapted for physically
frail patients and those with mild cognitive impairment, but
further research is needed. Use of psychotherapy is often
guided by the patient preference and the availability of
clinicians with appropriate training and expertise in specific
psychotherapeutic approaches. In terms of clinical factors,
psychotherapy is usually recommended for elderly patients
with mild to moderate depression who have evidence of
stressful life events, family conflicts, and the reduction or
absence of social support. In a country like India, where
there is scarcity of trained psychotherapists, clinicians
can also use psycho-educational approach and supportive
psychotherapy. In general the basic principle which should
guide any kind of supportive psychotherapy should involve
use of adaptive strengths that have served the patient well
in the past, increasing the patient’s self-esteem, accepting
feelings at face value, holding the prospect of hope and
accepting anger and irritability.
While using psychotherapy, the frequency of sessions must
be guided by type and goals of the psychotherapy, the
frequency necessary to create and maintain a therapeutic
relationship, the frequency of visits required to ensure
treatment adherence, and the frequency necessary to monitor
and address suicidality. Other factors which also influence
the frequency of psychotherapy sessions include severity
of illness, the patient’s cooperation with treatment, the
availability of social supports, cost, geographic accessibility,
and presence of comorbid general medical problems.
Regardless of the type of psychotherapy selected, the response
to treatment should be carefully monitored and if the patient’s
condition fails to stabilize or deteriorates, reassessment
needs to be carried out. If after 4–8 weeks of treatment at
least a moderate level of improvement is not observed,
then a thorough review and reappraisal of the diagnosis,
complicating conditions and issues, and treatment plan
should be conducted. In many cases, the treatment plan can
be revised by the addition or substitution of pharmacotherapy.
Following any revision or refinement of treatment, the patient
should continue to be closely monitored.
Medications plus psychotherapy: Available data supports
the superiority of the combined treatment over the use
of monotherapies. Selection of pharmacotherapy and
psychotherapy in patients considered for combined treatment
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must be guided by the same variables, which determine the use
of these treatments as monotherapies. While using combined
treatment, same doses of antidepressant medication and
the same frequency and course of psychotherapy should
be used as is employed for patients receiving these as a
monotherapy. Patients receiving combined antidepressant
medication and psychotherapy should also be monitored
closely for treatment effect, side effects, clinical condition,
and safety. If after 4–8 weeks, there is not at least a moderate
improvement, a thorough review should be conducted,
including of the patient’s adherence and pharmacokinetic/
pharmacodynamic factors affecting treatment. The treatment
plan can be revised by using many of the same therapeutic
options described for patients who have not responded to
treatment with either modality alone. Following any change
in treatment, the patient should be monitored, and if at least
a moderate improvement is not seen after an additional 4–8
weeks of treatment, another thorough review should be
carried out.
Improve Social Support/family support: Addressing the
issue of social support in elderly patients with depression is
very important. In many elderly patients psychosocial issues
like social isolation, neglect by the family etc contribute to
the onset and or continuation of depression. Accordingly
efforts must be made to improve the social support of
the patient. Family members must be encouraged to
provide emotional support and affection. Family members
must be asked to show patience, listen to the patient, be
understanding and encouraging. If patient expresses suicidal
ideations, plans or talks about death, than they should
Figure-4: Treatment algorithm for inadequate response to first
antidepressant therapy in elderly
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Avasthi and Grover: Management of Depression in Elderly
take it seriously and family members should liaise with the
treating agencies. Family members must be informed that
they should refrain from being critical. Family members can
also help in supervising the medications.
Life style modifications: Besides pharmacotherapy,
psychotherapy and improving social support, it is important
to look at the life style issues and patients must be
encouraged to maintain a regular activity schedule, go for
walks depending on the physical health status, socialize and
engage themselves cognitively.
Other interventions: There is some data to suggest that
aerobic exercises have a positive effect on depressive
symptoms, executive function and psychological well being.
It has also been shown that Yoga and mindfulness-based
exercises can increase sense of emotional and physical
wellbeing. Spirituality, religious beliefs and involvement
with a faith group may be protective against development
of mental illness while at the same time provide avenues for
increased social connectedness.
CONTINUATION PHASE
Aim of continuation phase treatment is to prevent relapse
of depression and the same treatment as used during the
acute phase need to be continued (Figure-5). During the
continuation phase, patients who have been treated with
antidepressant medications in the acute phase should be
maintained on the same agent on the same dose. Although
there is scarcity of data about use of psychotherapy in the
continuation phase to prevent relapse, some experts support
the use of a specific effective psychotherapy during the
continuation phase. Use of ECT in the continuation phase
has received little formal study. There is no consensus on the
duration of continuation phase in elderly, but some experts
suggest that treatment should be continued for 1 year after
remission. The frequency of visits must be determined by the
patient’s clinical condition as well as the specific treatments
being provided. For stable patients in whom the visits are
for the purpose of providing psychiatric management, the
frequency could be once every 2 weeks to 2 months. For
other patients, such as those in whom active psychotherapy
is being conducted, the frequency required may be as high
as multiple times a week. If maintenance phase treatment
is not indicated for patients who remain stable following
the continuation phase, patients may be considered for
discontinuation of treatment. If treatment is discontinued,
patients should be carefully monitored for relapse, and
treatment should be promptly reinstituted if relapse occurs.
MAINTENANCE PHASE
As in young adults, the risk of recurrence is high among
elderly, with rates of recurrence of 50 to 90 percent over a
period of two to three years; hence, the goal of treatment
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Avasthi and Grover: Management of Depression in Elderly

Figure-5: Treatment algorithm for continuation phase treatment of depression in elderly

should be not only to treat current episode, but also be

prevention of recurrence in future. There is no consensus
regarding the duration and when to give and when not to
give maintenance treatment in elderly. There is agreement to
large extent that patients who have history of three or more
relapses or recurrences should be given long-term treatment,
but maintenance treatment after 2 episodes is still debated.

In general, the treatment which was effective during

the acute and continuation phases should be used in the
maintenance phase (Figure-6). The same full antidepressant
medication doses should be used. For psychotherapy
during maintenance phase, treatments can involve fewer
visits (e.g., once a month). Although the effectiveness Figure-6: Treatment algorithm for continuation phase
of combinations of antidepressant medication and treatment of depression in elderly
psychotherapy in the maintenance phase has not been well
studied, such combinations may be an option for some the frequency and severity of recurrences, tolerability of
patients. The frequency of clinic visits in maintenance treatments, and patient preferences. For some patients,
phase can vary from once every several months for stable maintenance treatment may be required indefinitely.
patients who require only psychiatric management and
medication monitoring to as high as once or twice per week DISCONTINUATION OF ACTIVE TREATMENT
in those who are either receiving psychotherapy or severely
medically compromised. The optimal length of maintenance The decision to discontinue maintenance treatment should
treatment is not known and may also vary depending on be based on the probability of future recurrence, the

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Avasthi and Grover: Management of Depression in Elderly

Table-15: The antidepressant discontinuation syndrome frequency and severity of previous episodes, the persistence
Mnemonic for clinical presentation of depressive symptoms after recovery, presence or absence
F  Flu-like symptoms of comorbid physical illnesses and psychiatric disorders, and
I  Insomnia
N  Nausea
patient preferences. If the decision is made to discontinue
I  Imbalance or terminate psychotherapy in the maintenance phase, it
S  Sensory disturbances (e.g., electrical sensations) needs to be individualized as per the patient’s needs. In case,
H  Hyperarousal (agitation)
it is decided to discontinue pharmacotherapy, it is advisable
Table-16: Management of Depression in Special Situations
Special Situation Strategy
Suicidal Behaviour • Assess for risk
• If the suicidal risk is present- increase the surveillance, high risk management, no suicide contract
• If required admit, consider ECT
Psychotic features • Use combination of antidepressants and antipsychotics, if required augment with lithium
• Consider ECT
Catatonic features • Use benzodiazepines, if no or partial response, consider ECT
Alcohol or Substance Abuse/ • Evaluate the relationship of depressive symptoms with intoxication, withdrawal
dependence • Look for comorbid psychiatric disorder, liver disease and other systemic complications of substance use
• Consider hospitalization, if the depression is severe, patient is suicidal, not able to abstain
• Detoxification, relapse prevention counselling
• Adjust the doses of antidepressants considering the hepatic decompensation
Comorbid panic and anxiety • Anxiety symptoms often accompany depression
disorder • Few patients may have comorbid anxiety disorders
• SSRIs and TCAs can worsen anxiety initially, consider use of benzodiazepines during the initial phase
• Can consider augmentation with buspirone
MDD–related cognitive • Evaluate thoroughly to distinguish between dementia and pseudodementia
dysfunction (pseudodementia) • Adequate management of MDD leads to improvement in features of pseudodementia
Major Psychosocial Stressors • Consider use of psychotherapeutic intervention with or without antidepressants depending on the severity of depression
• If the adverse life situations requires removing the patient from stressful situation- consider inpatient care
Family distress • Ambivalent, abusive, rejecting, or highly dependent family relationships may particularly predispose an individual to MDD
• Consider family therapy, in conjunction with individual psychotherapy and pharmacologic therapies
• If required short term inpatient care may be considered
Bereavement • Proper evaluation for suicidality
• Psychotherapeutic interventions
Cardiac disease • Patients with known cardiac problem need to be monitored for the emergence of cardiac symptoms, ECG changes, or
orthostatic blood pressure decrements
• Liaison with the cardiologist before and during antidepressant medication treatment may be advisable, especially, in the
background of recent myocardial infarction
• Consider drug interactions, side effects (risk of bleeding) while choosing antidepressants
• If possible, avoid TCAs
• Monitor the cardiac status closely
• SSRIs, Bupropion, and ECT appear to be safer for patients with pre-existing cardiac disease
• Use of ECT may require consultation with a specialist and treatment modification before use
• Monitor ECT while using SSRIs or other antidepressants to evaluate arrthymias, bradycardia, hypotension,
hypertension (venlafaxine)
Hypertension • Evaluate for the possibility of medication induced depression, if required change the antihypertensive
• Consider drug interactions while choosing antidepressants
• Consider issues like precipitation of SIADH (hyponatremia), hypotension, risk of bleeding while choosing
antidepressants
• Venlafaxine can lead to hypertension, closely monitor the blood pressure
Diabetes mellitus • SSRIs may reduce blood glucose level by upto 30%
• Avoid fluoxetine in patients with type-II diabetes mellitus
• TCAs can increase the blood glucose levels
• Some of antidepressants: beneficial in management of diabetic neuropathy
• Lithium can be used safely in patients without renal disease
Asthma • Consider the possibility of medication induced depression
• Avoid MAOIs
Dementia • Proper assessment: use of scales specific to assessment of depression in patients with dementia
• Use antidepressants withlowest possible degree of anticholinergic effect, e.g., bupropion, fluoxetine, sertraline, and, of
the tricyclic agents, desipramine or nortriptyline.
• Among SSRIs, avoid paroxetine
• Alternatively, some patients do well given stimulants in small doses
• ECT is also effective in MDD superimposed on dementia, and can be used if medications are contraindicated, not
tolerated, or if immediate resolution of the MDD is medically indicated (such as when it interferes with the patient’s
acceptance of food)

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Avasthi and Grover: Management of Depression in Elderly

Special Situation
Glaucoma
Post-stroke Depression
Obstructive uropathy
Parkinson’s disease
Malignancy
Drug induced depression
Liver disease
Renal disease
Table-16: Contd...
Strategy
• Most common type of glaucoma in elderly is acute close angle glaucoma
• Monitor intraocular pressure
• Antidepressants with anticholinergics, serotonergic or adrenergic properties can cause or exacerbate acute close angle
glaucoma
• Antidepressants lacking anticholinergic and serotonergic activity (bupropion) should be used
• Post stroke depression seen in at least 30‑40% of survivors of intracerebral hemorrhage.
• Proper identification and adequate management of depression can aid in faster rehabilitation
• Consider the possibility of medication associated depression- if required change the drugs
• Consider drug interactions and side effects while choosing antidepressants
• Fluoxetine and nortriptyline are probably the most standard and seen to be effective.
• Antidepressants with antimuscarinic effects should be avoided in patients with prostatism and other forms of bladder
outlet obstruction
• Benzodiazepines, trazodone, and MAOIs may also retard bladder emptying
• The antidepressant medications with the least propensity to cause bladder outlet obstruction are SSRIs, bupropion, and
desipramine
• In terms of efficacy, available data suggest that TCAs are more efficacious than SSRIs
• However, because of tolerability issues, SSRIs are recommended as the first line agents
• Bupropion may be beneficial but can lead/worsen psychosis
• If used TCAs like desipramine and nortriptyline may be preferred
• ECT can be used in patients with severe depression; ECT exerts a transient beneficial effect on the symptoms of
idiopathic Parkinson’s disease in many patients
• Avoid: Amoxapine, lithium
• Risks factors for depression in patients with malignancy includes advanced disease, pain, tumor site, social factors,
psychological factors, psychiatric morbidity, and treatment related factors
• High prevalence of depression in patients with pancreatic (50%), oropharyngeal (22-40%) and breast cancer patients
(18-36%)
• Paraneoplastic syndromes particularly which lead to hypothyroidism, hypercortisolism etc. can also lead to
development of depression
• Various social factors like social isolation, recent losses, and socio-economic pressures can contribute to development
of depression
• Medications used for management of various malignancies can also lead to development of depression
• SSRI are considered to be the first line drugs; also beneficial in managing neuropathic pain
• Consider concomitant medications, drug interactions and organ failure/impairments while choosing antidepressants
• Psychostimulants, with their rapid onset of action have some advantages for depressed cancer patients in the sense of
promoting a sense of well being, decreasing fatigue, stimulating appetite, potentiating the analgesic effect of opioids
and decreasing opioid induced sedation
• Psychological interventions with a focus to reduce emotional distress, improve morale, coping ability, self-esteem and
sense of control
• Improve social support
• If medication induced depression is considered, then if possible the suspected medication need to be discontinued and
replaced with another agent less likely to induce depression
• When discontinuation of the medication is not possible or when discontinuation does not lead to remission of the
depression, pharmacotherapy for the depression should be considered
• While considering antidepressants, evaluate the severity of liver disease, concomitant medications, clinical features
which can worsen with use of antidepressants (constipation, hepatic encephalopathy), chances of bleeding, other organ
dysfunction or physical comorbidities
• Liver impairment affects basic elements of medication pharmacokinetics, from absorption to metabolism, distribution
to elimination, changing drug levels, duration of action, and efficacy
• Most antidepressants are highly protein-bound, except, venlafaxine, and methylphenidate; in presence of hepatic
impairment higher levels of free pharmacologically active drug is available in the blood, faster clearance
• Avoid drugs which can cause sedation and constipation: can precipitate hepatic encephalopathy
•  Preferred antidepressant: escitalopram
• Avoid sertraline, MAOIs (these can be hepatotoxic and may precipitate coma)
• When used, venlafaxine, nefazodone, mirtazapine and reboxetine should all be started at a low dose with cautious
titration
• Lithium can be used safely
• Start in lowest possible doses, closely monitor the patients while using antidepressants
• While considering antidepressants, evaluate the severity of renal impairment, concomitant medications, clinical features
which can worsen with use of antidepressants (electrolyte imbalance, uremic encephalopathy), chances of bleeding,
other organ dysfunction or physical comorbidities
• TCAs are considered to safer than SSRIs
• Avoid Lithium
• Start in lowest possible doses, closely monitor the patients while using antidepressants

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Avasthi and Grover: Management of Depression in Elderly

Special Situation
Perioperative period
Table-16: Contd...
Strategy
• Antidepressants can interact with anaesthetic agents and lead to complications when during the perioperative periods
• Antidepressants can theoretically increase the risk of bleeding during the surgery, interact with medications used during
the surgery and lead to serotonin syndrome
• TCAs & MAOIs: gradually discontinue over 2 weeks before surgery
• Lithium: to be discontinued 72 hours prior to surgery
• SSRI should not be discontinued in order to prevent anesthetic interactions, except when the SSRI is used in
combination with aspirin or an NSAID and when the SSRI is used in patients over 80 years of age; however, in these
patients, the balance of risks of withdrawal and bleeding should be discussed with patients
• Start antidepressants during the post-operative period when patient is hemodynamically stable, is able and allowed to
drink, and is not on new, potentially interfering drugs

to taper the medication over the period of at least several
weeks to few months. Such tapering allows for the detection
of emerging symptoms or recurrences when patients
are still partially treated and can help in returning to full
therapeutic intensity. In addition, tapering also minimizes
the risks of antidepressant medication discontinuation
syndrome. Discontinuation syndrome is more frequently
reported after discontinuation of medications with
shorter half-lives. Accordingly, short-acting agents should
be tapered more slowly. Paroxetine, venlafaxine, TCAs,
and MAOIs tend to have higher rates of discontinuation
symptoms while bupropion-SR, citalopram, fluoxetine,
mirtazapine, and sertraline have lower rates. The symptoms
of antidepressants discontinuation are given in Table-15.
Reassurance may be sufficient for mild discontinuation
symptoms. However, for mild to moderate discontinuation,
short-term symptomatic treatment (analgesics, antiemetics,
or anxiolytics) may be beneficial. If the discontinuation
syndrome is severe, antidepressant should be reinstated
and tapered off more slowly.
After the discontinuation of active treatment, patients
should be informed about the potential risk of relapse of
depression. Early signs of depression should be reviewed,
and a plan for seeking treatment in the event of recurrence of
symptoms should be established. Patients should continue
to be monitored over the next several months to identify
those in whom a relapse has occurred. If a patient suffers
a relapse upon discontinuation of medication, treatment
should be promptly reinitiated. In general, the previous
treatment regimen to which the patient responded in the
acute and continuation phase should be considered.
MANAGEMENT OF TREATMENT RESISTANT
DEPRESSION
The term Treatment resistant depression (TRD) is usually
used, when the depression fails to respond to two adequate
trials of antidepressant medications. It is estimated that only
half of the elderly patients respond to first line treatment and
<49% achieve remission. The poor response to treatment is
usually attributed to the vascular component in the etiology
of late onset depression. Available evidence has also shown
association of cognitive impairment, especially executive
dysfunction with poor treatment response among elderly.
Many other factors also contribute to TRD. However, prior
to considering a person to be having TRD, it is important
to evaluate the patient properly. Initial reassessment need
to focus on re-evaluating the diagnosis of depression. Next
step involves evaluation of the fact that patient has received
adequate doses of the antidepressant medications for the
adequate duration with good compliance. Underlying
organic factors need to be evaluated and if these are
reversible (e.g., nutritional deficiencies), these must be
addressed. Management of TRD involves either change of
medication or augmentation of ongoing antidepressant
medication. In term of augmentation strategies, although
it has not been evaluated thoroughly, lithium is usually
recommended as the first choice. When used the target
serum levels of lithium for elderly must be in the range
of 0.5 to 0.6 mmol/L and it need to be continued for a
period of at least 1 year after achieving remission. There is
some data to suggest the efficacy of aripiprazole in elderly
patients with treatment refractory depression, when used
as an augmenting agent with venlafaxine.
TREATMENT IMPLICATIONS OF CONCURRENT
GENERAL MEDICAL DISORDERS
Many elderly patients present with physical illnesses which
require special attention. Similarly, certain clinical situations
also influence the decision making. Management in some of
these difficult situations is summarized in table-16.
REFERENCES
1. Alexopoulos GS, Katz IR, Bruce ML, Heo M, Have TT, Raue P et al.
Remission in depressed geriatric primary care patients: a report from the
PROSPECT study. Am J Psychiatry 2005;162(4):718-24
2. Avasthi A, Grover S, Bharadwaj R. Clinical Practice guidelines for
treatment of depression in old age. (Eds): Shiv Gautam & Ajit Avasthi.
Published by Indian Psychiatric Society, 2007; Volume III, 51-150
3. Boylan LS, Haskett RF, Mulsant BF, et al. Determinants of seizure
threshold in ECT: Benzodiazepine use, anesthetic dosage, and other
factors. J ECT, 2000; 16: 3-18.
4. Bruce ML, Seeman TE, Merrill SS, et al. The impact of depressive
symptomatology on physical disability: MacArthur Studies of Successful
Aging. Am J Public Health, 1994; 84:1796-1799.
5. Calati R, Salvina Signorelli M, Balestri M. Antidepressants in elderly:
metaregression of double-blind, randomized clinical trials. J Affect Disord
2013; 147:1–8
6. Charles III FR, Kupfer DJ, Hoch CC, Stack JA, Houck PR, Sewitch
DE. Two-year follow-up of elderly patients with mixed depression and

Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018 S361

[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]
Avasthi and Grover: Management of Depression in Elderly
dementia. Clinical and electroencephalographic sleep findings. J Am
Geriatr Soc 1986;34:793–9
7. Clayton AH, Kennedy SH, Edwards JB, Gallipoli S, Reed CR. The effect
of vilazodone on sexual function during the treatment of major depressive
disorder. The journal of sexual medicine. 2013 Oct 1;10(10):2465-76
8. Cole MG, Bellavance F, Mansour A. Prognosis of depression in elderly
community and primary care populations: a systematic review and meta-
analysis. American Journal of Psychiatry. 1999 Aug 1;156(8):1182-9
9. Cole MG, Dendukuri N. Risk factors for depression among elderly
community subjects: a systematic review and metaanalysis. Am J
Psychiatry 2003;160:1147–56.
10. Cuijpers P, Geraedts AS, van Oppen P, Andersson G, Markowitz JC, van
Straten A. Interpersonal psychotherapy for depression: a meta-analysis.
Am J Psychiatry. 2011 Jun;168(6):581-92.
11. Flint AJ, Gagnon N. Effective use of electroconvulsive therapy in late-life
depression. Can J Psychiatry 2002;47(8):734–41
12. Garekar H, Grover S. Electroconvulsive therapy in the elderly: Anaesthetic
considerations and psychotropic interactions. J Geriatr Ment Health 2017
(in Press)
13. Gautam S, Jain A, Gautam M, Vahia VN, Grover S. Clinical practice
guidelines for the management of depression. Indian J Psychiatry. 2017
Jan;59(Suppl 1):S34
14. Geiselmann B, Bauer M. Subthreshold depression in the elderly:
Qualitative or quantitative distinction? Compr Psychiatry, 2000; 41(2 suppl
1):32-38.
15. Glover JA, Srinivasan S. Assessment and treatment of late-life depression.
JCOM. 2017;24(3):135-144
16. Grover S, Malhotra N. Depression in elderly: A review of Indian research.
J Geriatr Ment Health 2015;2:4-15
17. Grover S, Somaiya M. ECT in the Elderly: A Review. J Geriatr Ment Health
2017 (in Press)
18. Judd LL, Hagop SA, Maser JD et al. A prospective 12 year study of
subsyndromal and syndromal depressive symptoms in unipolar major
depressive disorders. Arch Gen Psychiatry, 1998; 55:694-700.
19. Kok RM, Heeren TJ, Nolen WA. Continuing treatment of depression in
the elderly: a systematic review and metaanalysis of double-blinded
randomized controlled trials with antidepressants. Am J Geriatr Psychiatry.
2011;19: 249-255
20. Kok RM, Nolen WA, Heeren TJ. Efficacy of treatment in older depressed
patients: a systematic review and meta-analysis of double-blind
randomized controlled trials with antidepressants. J Affect Disord 2012;
141:103–115.
21. Kok RM, Nolen WA, Heeren TJ. Efficacy of treatment in older depressed
patients: a systematic review and meta-analysis of double-blind
randomized controlled trials with antidepressants. J Affect Disord 2012;
141:103–115.
22. MacQueen GM, Frey BN, Ismail Z, Jaworska N, Steiner M, Lieshout RJ et
al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016
clinical guidelines for the management of adults with major depressive
disorder: section 6. special populations: youth, women, and the elderly.
Can J Psychiatry 2016;61(9):588-603
23. Mulsant BH, Blumberger DM, Ismail Z, Rabheru K, Rapoport MJ. A
S362
systematic approach to pharmacotherapy for geriatric major depression.
Clinics in geriatric medicine. 2014 Aug 31;30(3):517-34
24. National Institute for Health and Clinical Excellence (NICE). Depression:
management of depression in primary and secondary care (Clinical
guideline 23) (2004)
25. Olin JT, Schneider LS, Katz IR, et al. Provisional diagnostic criteria for
depression of Alzheimer disease. Am J Geriatr Psychiatry. 2002;10:125–
128.
26. Pinquart M, Duberstein PR, Lyness JM. Treatments for late-life depressive
conditions: a meta-analytic comparison of pharmacotherapy and
psychotherapy. Am J Psychiatry 2006;163:1493–501
27. Rangaswamy SM. Geneva, Switzerland: The World Health Organization.
World Health Report: Mental Health: New understanding New Hope,
2001.
28. Riva-Posse P, Hermida AP, McDonald WM. The role of electroconvulsive
and neuromodulation therapies in the treatment of geriatric depression.
Psychiatr Clin North Am .2013 Dec 31;36(4):607-30
29. Sahoo S, Grover S. Hyponatremia and psychotropics. J Geriatr Ment
Health 2016;3:108-22
30. Tedeschini E, Levkovitz Y, Iovieno N, et al. Efficacy of antidepressants
for late-life depression: a meta-analysis and meta-regression of placebo-
controlled randomized trials. J Clin Psychiatry. 2011;72:1660-1668
31. Wen XJ, Wang LM, Liu ZL. Meta-analysis on the efficacy and tolerability of
the augmentation of antidepressants with atypical antipsychotics in patients
with major depressive disorder. Braz J Med Biol Res 2014;47:605–16
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PREAMBLE OF THE CLINICAL PRACTICE GUIDELINES FOR ELDERLY
In last one decade, several developments have occurred in
the area of management of various psychiatric disorders
among elderly. Hence, it was decided to update the existing
Clinical Practice Guidelines (CPGs) for various psychiatric
disorders. These new set of CPGs is an attempt to update
the previous guidelines by emphasizing what is new in
the field. It is suggested that these guidelines should be
read in conjunction with the earlier version of the CPGs as
developed and published by the Indian Psychiatric Society
in the year 2007.
It is important to note that these guidelines are not specific
to any specific treatment setting and these may require
minor modifications to address the treatment needs of
patients in a specific setting. It is well known that a host
of factors influence the management of various psychiatric
disorders. Particular consideration needs to be given to
clinical parameters like cross-sectional and longitudinal
course of symptoms, type and severity of symptoms,
presence or absence of medical and psychiatric comorbidity,
comorbid substance abuse/dependence and special needs.
Socio-cultural factors like, beliefs about the illness and their
treatments are particularly important, as are the availability
of treatment-resources and social support. Accordingly,
the recommendations made as part of these CPGs have
to be tailored to suit the needs of individual patients. It
is expected that these guidelines will act as a framework
to manage an elderly patient rather than management of a
disorder. The recommendations given as part of the revised
guidelines are based on the available evidence base, expert
consensus and the feedback obtained from the membership.
S300
The general goals of treatment should be to decrease the
frequency, severity and impact of episodes (exacerbations)
and maximize functioning. Specific goals will depend on
the specific symptoms, phase of the illness and available
resources.
Shiv Gautam, Ajit Avasthi1, Sandeep Grover1
Director and Professor, Gautam Institute of Behavioral
Sciences and Alternative Medicine, Jaipur. 1Department of
Psychiatry, Post Graduate Institute of Medical Education and
Research, Chandigarh, India. dr_shivgautam@yahoo.com
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Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
Access this article online
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www.indianjpsychiatry.org
DOI:
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How to cite this article: Gautam S, Avasthi A, Grover S.
Preamble of the Clinical Practice Guidelines for Elderly. Indian
J Psychiatry 2018;60:300.
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IJP EDITOR SPEAKS
Clinical Practice Guidelines for Elderly
T.S. Sathyanarayana Rao
Professor, Department of Psychiatry, JSS Medical College and Hospital, JSS University, MG Road, Mysore ‑ 570 004,
Mysore. tssrao19@yahoo.com
Population ageing is an inevitable reality. Worldwide the
geriatric population comprises of about 11% of the total
world population, and is projected to increase to about 22
percent by 2050. With declining fertility rates, reduction
in mortality rates and increased life expectancy the elderly
population constitutes as one of the fastest growing age
segments. India too is witnessing a similar trend. It is
estimated that the elderly population will increase from 8
percent (2015) to 19 % by 2050.
Ageing has led to an increase in prevalence of chronic
non-communicable diseases/disorders and hence
increased demands on health care services. Geriatric
patients have different and diverse needs from the
younger population.
Although, a larger number of physicians and clinicians are
practicing in India but only a few clinicians are specially
trained to deal with the ageing population. Geriatric
population have diverse and different health care needs
from the younger population. One such common example
is the presence of sleep changes in elderly which may
be in part due to the lack of structure in daily activities
after retirement leading to laxity in sleeping habits with
erratic wake up time, being awake in the middle of the
night, early morning awakening (more commonly seen
than younger population). The goal of treatment of sleep
disturbances in Late Life Depression also changes a little,
for example one of the behavioural targets include earlier
bedtime and an earlier rising time as the clock time for
sleeping period becomes earlier and earlier.
This Clinical Practice Guidelines (CPGs) developed by
the task force on CPGs and its editors address the needs
of ageing population covering the most commonly
encountered psychiatric issues like Dementia, Psychosis,
Sleep Disorders, Depression, Anxiety disorders, Delirium,
Sexual Behaviour and Rehabilitation needs and their
management in a complete yet concise manner which is
easy to understand and apply in a busy clinical setting.
The handbook starts with one of most important clinical
© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
tool –The Geropsychiatric Clinical Interview which
encompasses interviewing skills, detailed history taking
including the presenting complaints, past psychiatric
and medical history, the tools and algorithms important
for assessment and forming a diagnosis of Psychiatric
Disorders in the Elderly. The chapter on elderly sexuality
emphasises on sexual life which is of paramount
importance in expression of love, passion, intimacy and
emotional bonding during later years, it also elaborates
on approaching the elderly patient (or couple in some
cases), building enough rapport to elicit sexual history,
taking precise and detailed sexual history, and appropriate
Psychological and Pharmacological management of sexual
disorders including the recent advances. The chapter
on Depression differentiates myriad of presentations
such as recurrent depression coming from early onset
depression, late life depression which has chronic course,
worse prognosis with higher relapse rates and lastly
mood disorders secondary to general medical condition
or substance use and their management. The chapter
on Dementia and Anxiety disorders lays importance on
picking up and diagnosing these disorders as they are
commonly ignored, underdiagnosed and left untreated
in elderly. It also gives detailed algorithms for treatment
choices including psychotherapy and pharmacotherapy
including dosage, titration and tapering of drugs. As
the person ages the metabolism of the body changes
and so does the renal and the liver functions, any slight
change e.g. a stressor or electrolyte imbalances may
cause psychoses and delirium respectively in elderly.
These should be managed with utmost care as the
pharmacodynamics and pharmacokinetics changes as the
people age, hence a small dosage of drug may be needed
and titrated, this preferred treatment concept of “starting
low and going slow” has been extensively discussed in
chapters on Delirium and Psychoses. Finally rehabilitation
needs of elderly including psychosocial interventions,
cognitive remediation and other models which have
been potentially effective in improving the functioning
and quality of life in elderly is discussed in this treatise.
We hope that these guidelines would help in facilitating
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Clinical Practice Guidelines for Elderly

proper management of elderly patients presenting with Access this article online
various types of disorders and that the information Quick Response Code
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provided will be of interest and may serve as a powerful
www.indianjpsychiatry.org
tool to healthcare professionals.

The editorial team of IJP is grateful to the CPG task force DOI:
on Geriatric Psychiatry and its editors for the opportunity 10.4103/0019-5545.224468

to publish the same in IJP.

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others to remix, tweak, and build upon the work non‑commercially, as long as the
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Guidelines for Elderly. Indian J Psychiatry 2018;60:297-8.
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Clinical practice guidelines for Geriatric Anxiety Disorders

Alka A. Subramanyam, Jahnavi Kedare, O.P. Singh1, Charles Pinto
Department of Psychiatry, TNMC & BYL Nair Charitable Hospital, Mumbai, India, 1Department of Psychiatry, NRS Medical
College, Kolkata alka.subramanyam@gmail.com

INTRODUCTION caregiver, keeping the following in mind:

a) Fears and concerns as a part of normal aging e. g.
Anxiety is one of the most common symptoms seen in Limited mobility in an elderly leading to avoidance
the elderly. Sub-syndromal anxiety is more prevalent of going out of the house
than depression and cognitive disorders. The commonest b) Anxiety associated with dementia
anxiety disorder seen in the clinical practice is Generalised c) Medical disorders which may mimic anxiety
Anxiety Disorder(GAD)(7.3%) followed by phobias(3.1%), symptoms.
the panic disorder(1%) and Obsessive Compulsive
Disorder(OCD)(0.6%). Two relatively recent Indian studies Table 1: Classificatory Systems for Anxiety Disorders
have demonstrated an overall prevalence of anxiety ICD 10 DSM 5
disorders to be10.8% and 10.7%, respectively. Thus anxiety
(F40) Phobic anxiety disorders Anxiety Disorders
is quite common in the elder, among all the disorders of (F40.0) Agoraphobia Separation anxiety
the geriatric population. (F40.1) Social phobias disorder
o Anthropophobia Selective mutism
These clinical practice guidelines intend to provide the o Social neurosis Specific phobia
practicing psychiatrists a ready reckoner to identify anxiety (F40.2) Specific (isolated) phobias Social phobia
o Acrophobia Panic disorder
disorders, assess them, treat and manage side-effects of o Animal phobias Agoraphobia
medications among elder individuals. o Claustrophobia Generalized anxiety
o Simple phobia disorder
The classificatory systems (Table 1) now have a difference (F40.8) Other phobic anxiety
as far as anxiety disorders are concerned, with DSM disorders
(F40.9) Phobic anxiety disorder,
5 introducing changes in the classification of anxiety unspecified
disorders. o Phobia NOS
o Phobic state NOS
On the basis of their distinct clinical features anxiety (F41) Other anxiety disorders
disorders can be divided into three categories. (F41.0) Panic disorder (episodic
paroxysmal anxiety)
(F41.1) Generalized anxiety disorder
1) Worry/distress disorders- GAD, PTSD, Acute stress (F42) Obsessive-compulsive Obsessive-Compulsive
disorder disorder Disorders(Separate
2) Fear disorders- Panic disorder, phobia classification)
3) OCD Obsessive-compulsive
disorder
Body dysmorphic disorder
Since we are used to evaluating younger individuals, the Hoarding disorder
usual symptoms we expect might not be seen in the elder. Trichotillomania
Commonly seen differences between the young and the old Excoriation disorder
in the presentation of anxiety are shown in Table-2.
(F43) Reaction to severe stress, and Trauma and
adjustment disorders Stressor-Related
Assessment (F43.0) Acute stress reaction Disorders(Separate
A comprehensive assessment of anxiety disorders includes (F43.1) Post-traumatic stress disorder classification)
interviewing the older adult and her/his caregiver. There is Reactive attachment
disorder
a tendency to underplay or normalize certain behaviours,
Disinhibited social
which may be indicative of anxiety for e.g., avoidance to engagement disorder
go out of the house or fear of falls. It is thus important Post Traumatic Stress
to assess not only the severity of these symptoms; but Disorder
also impairment in functioning because of the symptoms. Acute stress disorder
Adjustment disorder
This can be achieved by interviewing the patient and the

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Alka Subramanyam et al: Geriatric Anxiety Disorders

d) Co-morbidities like cardiac illness, depression,
malignancy, Parkinson’s disease, auto-immune
disorders, collagen vascular diseases, endocrine
disorders etc.
e) Clinical presentation in young adults and elderly
differs. For e.g., in elderly phobia is experienced
as a fear of situations or inanimate stimuli, such as
lightening whereas among young people phobia is
usually of animals.
f) The ‘worried well’ Worry as a symptom in older
adults, independent of a diagnosable disorder.
The hallmark of any complete assessment starts with a
detailed history.
History: The following points(Table 3) need to be kept in
mind while detailing a history of elder anxiety, to give a
clearer picture. The basic history forms a base or a skeleton
on which we have to build the further points which will
lead us systematically towards a diagnosis. Elder individuals
are considered to be a vulnerable population, and it is this
vulnerability which makes them at risk to develop anxiety.
Multiple risk factors have been identified, which are known
to be associated and specific anxiety disorders (Table-4).
A comprehensive history and assessment of risk factors
will be the most important ingredients towards making a
diagnosis of the specific anxiety disorder that will emerge
as a diagnosis. While narrowing down on the same, the
specific characteristics that one can look for, in elder
individuals, when one looks for the symptoms of various
disorders, are highlighted below(Table 5). The disorders
appear from common to uncommon, as seen from various
population studies.
Any psychiatric history cannot be complete without the
inclusion of negative history too. Anxiety is such a pervasive
symptom, that it not only is seen in specific anxiety disorders,
but can be seen in other psychiatric disorders, as well as many
medical disorders(Table 6). An astute clinician will keep an eye
out for the same, and eliminate that whilst taking the history.
It is not only medical disorders that one must rule out.
Usually elder individuals are already on
medications for medical co-morbidities, commonest
being diabetes or hypertension. They may or may
not be on analgesics too. There are some drugs and
substances however, that are peculiar in contributing
to anxiety. A red flag on any of these would point

Table-2: Differences in clinical presentation of anxiety disorders among young and elderly patients
Young patients Old Patients
GAD in young and old has similar features consisting of muscle tension, worry, easy fatigability and sleep disturbances.
More severe panic symptoms Lower level of cognitive and somatic distress during a panic attack
OCD- More compulsive behavior involving counting or symmetry. More contamination and religious obsessions
PTSD- More severe psychological symptoms More severe physical symptoms, more impairment in social functions,
avoidance behaviour

Table-3: Pertinent issues in history while evaluating for Elder anxiety

History in detail
Medications that may trigger anxiety
Risk Factors for anxiety disorders among
Elderly
Psychological risk factors
· Interview patient and relative separately
· Socio-demographic details including marital status, occupational functioning, living
conditions, family type, source of income.
· Presenting illness: Onset, duration, progress
· Similar illness in the past
· Medical illnesses and treatment for the same
· Hearing and visual impairment
· Substance use(Substances of Abuse - cannabinoids, alcohol, ecstasy ; withdrawal
syndromes- alcohol, benzodiazepines, barbiturates, propranolol, anticholinergics, opiates,
SSRIs)
· Cognitive impairment
· Loneliness, Social support
· Activities of Daily Living e.g. bathing, dressing
· Limitations in activities (Functional limitations) e.g. difficulty in climbing stairs.
· Stressors like death of a close one
· Family history
Levodopa, Amantadine, Bromocriptine, Cycloserine, MAO inhibitors, TCAs, Theophylline,
Interferon, Thyroid hormones, Caffeine, Amphetamines, Methyl Phenidate, Sympathomimetics,
Phenylpropalamine.
Being female; low educational attainment; lower economic status; being childless; being single
or widowed; chronic medical illnesses; poor self-rated health; functional impairment; history of a
traumatic event especially in childhood
Neuroticism; poor coping skills; having another psychiatric disorder; low self-efficacy; impaired social
networks; cognitive impairment; presence of a major illness in the partner

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Table-4: Risk factors for various anxiety disorders in the elderly

Disorder Risk Factors
Panic Disorder Disability in old age
Phobic disorders Lower income, Early parental loss
Agoraphobia Female gender, widowed or divorced, presence of comorbid depression and social phobia
PTSD Female gender, childhood trauma, neuroticism, low self efficacy

Table-5: Specific presentations of various anxiety disorders in the elderly

Disorder Specific Characteristics in the Elderly
Specific phobia • Commonly seen
• Onset earlier in life, not in the geriatric age group
• Commonest symptom- Fear of falling
Generalized Anxiety Disorder • Commonest in elderly
• Again, usually early onset and chronic course
• Sub-syndromal symptoms more seen in the elder rather than the disorder per se.
• Commonest symptoms seen- Illness anxiety and health anxiety
Social Phobia • Again, usually early onset
• May be difficult to pick up due to reduced social networking and relative isolation.
Post-Traumatic Stress Disorder(PTSD) • Subsyndromal PTSD is more common in older adults
• Can be chronic
• Best evidence seen in war veterans
• In elder individuals-re-experience phenomenon are rare
Panic Attacks • Not so common, unlike younger age group, unless already pre-existing
• Diagnosable panic disorder is rare
• Overall functionality –less impeded than in younger adults as sympathetic overdrive reduces
• Existential anxiety can also manifest with panic attacks
Obsessive Compulsive Disorder • Onset after 55 years is very rare
• OCD may be seen as part of BPSD(Behavioural and Psychological Symptoms of Dementia)
• A peculiarity of this age is hoarding compulsions. Often seen with those having cognitive disorder,
personality change or substance use.

Table 6. Medical conditions in the elderly which can be mistaken for anxiety
System Specific Diseases
Neurological Stroke ,Parkinsonism ,epilepsy, multiple sclerosis, tumors
CVS Angina,mitral valve prolapse,cardiac arrhythmia,acute asthmatic attacks
GI disorders Irritable bowel syndrome
Metabolic /endocrine Hypoglycaemia,hyperthyroidism,pheochromocytoma,
hyparathyroidism,carcinoidsyndrome, uraemia, hepatic failure, hypocalcemia or hypercalcaemia
Deficiency states Vit. B1,B6,B12,folic acid

toward non-idiopathic anxiety, and prompt the treating
psychiatrist to first alter the existing prescription,
before staring yet another molecule and adding to the
prescription load.
It becomes important to liaison with the treating physician/
specialist to reduce/replace the suspected offending agent
with another acceptable molecule
As one can see, the history, along with medical and drug
history, can be quite exhaustive in the elderly, but to get
a comprehensive account, it is very much worthwhile
investing time into that.
Investigations
Elder individuals are prone to changes in metabolic
parameters and nutritional deficiencies, by virtue of a variety
of reasons which include decreased appetite, increased frailty
and drug-drug interactions. As a baseline, it is advisable to
rule out metabolic abnormalities(Table 7) such as:
Once the basic medical work-up and evaluation is done,
then a scale may be used to measure or quantify the anxiety,
which would also aid as a prognostic indicator. Various
anxiety rating scales(Table 8) have been used in elderly
to substantiate the diagnosis and to assess severity of the
disorder. These scales also assist in diagnosing anxiety
symptoms not amounting to a disorder. This is particularly
helpful as anxiety in elderly is under-diagnosed.
The choice of the scale would largely depend on the time
and purpose that it is being used for.
The Geriatric Anxiety Inventory has become the gold standard
for assessment in elder anxiety.

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At the end of the above exercise, one would be sufficiently the underlying cause of the anxiety, and our treatment may
equipped with a preliminary diagnosis or differential then show only a partial response.
diagnosis at the back of the mind.
Differential Diagnosis of Anxiety in Elder individuals(in
order of likelihood)
Whilst we come to a definite diagnosis, the following
1. Side Effects of Medication use, including self medication
differentials must be ruled out as these commonly will be
2. Drug and alcohol use
3. Medical comorbidities
Table 7: Investigations which may be done in a case of 4. Other Psychiatric disorders(including cognitive disorders)
Elder Anxiety
Baseline Trimming a prescription or changing medication might be a
CBC, challenge initially, the tricky aspects at times are when one
Blood sugar funnels down to a psychiatric diagnosis. Here, there are two
Urea ,
Creatinine
pertinent issues which often crop up while assessing the
Thyroid levels elder individual for anxiety. These are:
If indicated Sodium, 1. Distinguishing anxiety and depression in the
Potassium and elder(Table 9)
Calcium levels
Imaging if required
Chest Xray
This simple overview is very helpful in distinguishing the
ECG above
Echo Doppler
Based on individual case 2. Distinguishing anxiety from cognition(Table 10)
Pulse oximetry
Anxiety has reported high prevalence rates among people
Urine analysis and
Drug screening with dementia. It has a negative impact on cognitive
impairment and is associated with agitation and poor
quality of life. The presence of excessive anxiety can be
Table 8: Rating Scales for Geriatric Anxiety difficult to establish in people with dementia, especially
Type of Scale Name of Scale when expressive or receptive speech is impaired.
Observer Rated - Hamilton Anxiety Rating Scale
- Beck’s Anxiety Inventory Unfortunately, there is a lack of research on the treatment
- Anxiety Status Inventory
of anxiety in dementia, and also on the wider issue of the
Self- -Geriatric Anxiety Inventory
Rated(Unidimensional) -State-Trait Anxiety Inventory(The child management of anxiety disorders in old age. Behavioural
version of the scale is better to apply for the and psychological symptoms of dementia are not limited to
elderly) the later stages of the disease.
-State-Trait Inventory of Cognitive and
Somatic Anxiety
-Self Rating Anxiety Scale
The following comparative chart helps with clinical
Multi-dimensional Profile of mood states, Hopkins Symptom differentiation of the two.
Checklist(SCL-90 R).
Anxiety in Dementia - Rating anxiety in dementia scale (RAID), Once one has been able to differentiate between normal
BEHAV AD, E-BEHAV AD, NPI, NPI-Q.
ageing, anxiety, depression and a cognitive disorder or

Table 9: Comparative Symptom Overview for Normal Ageing versus Anxiety versus Depression in the Elder
Symptom Normal Ageing Major Depressive Disorder GAD/Panic Disorder/Phobia
Subjective Memory complaint + +++ ++
Excessive concern or worry __ ++ +++
Mood Disturbances __ +++ +/-
Changes in sleep pattern + ++ ++
Appetite disturbances Check for + __
concomitant
medication
Breathing difficulty Check for __ ++
concomitant
medication/
Respiratory ailment
like COPD
Anhedonia __ ++ __
Hopelessness __ ++ __

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Table 10: Comparative Symptom Overview for Late Life Anxiety versus Dementia
Behaviour Late Life Anxiety Dementia
Rigidity +/- +++
Hoarding +/- +++
Restlessness ++ ++
Psychomotor agitation ++ +++
Worry +++ --
Medically unexplained physical symptoms
+++ --
Sleep disturbances ++ +++
Being homebound Volitional Involuntary
Wandering away -- +++
Substance/Drug use(either recreational or + --
medical)

dementia, and come to a definitive diagnosis of anxiety
- one can then proceed on deciding how to manage the
patient.
Choice of treatment setting
Most of the anxiety disorders can be treated in outpatien
setting.
Inpatient management of anxiety disorders is indicated
when
1) Comorbid severe depression(and at times suicidality) is
present.
2) Anxiety disorder is severe and treatment resistant. e.g.
OCD.
3) In case of poor social support and presence of chronic
stressor separation from the stressful situation is
needed.
4) Concurrent medical illnesses and treatment need
evaluation and management.
Non-Pharmacological treatments
Treatment of geriatric anxiety actually involves
more of non-pharmacological approaches which are
first recommended rather than pharmacological
approaches. The usual non-pharmacological measures
advised are:
1. Lifestyle modification: Sleep, diet, exercise,
socialisation –all in moderation. Eliminate medical and
non-medical triggers
Structured daily activities are one of the mainstays of
elder care. The premise behind the same being, that
activities provide some stimulation and interaction with
the environment, give a sense of control and reduce overall
anxiety. Apart from managing one’s own daily routine, the
following are commonly advocated.
a) Physical Exercise: Regular physical exercise, even for
just a few minutes daily, improves cerebral blood flow
and metabolism. Sedentary individuals who are bound
to their beds have a distinct reduction in cerebral blood
flow. Exercise need not be strenuous in the form of
aerobic exercises or gym based exercises. A simple
walk in the garden or outdoors should suffice, that too
at the pace of the individual concerned. If wheelchair
bound, then upper body can be exercised with simple
stretches, use of a ball and hand exercises.
Other forms of physical exercise could include
- Walking in the house if too frail
- Swimming or aqua exercises or playing around in a
large tub to mobilize the limbs
- Physical games like playing ball, carrom, table tennis
etc
b) Sleep: We are aware that the sleep architecture gets
altered with advancing age, hence a shorter night time
sleep, phase advancement and more fragmented sleep
are all seen in the elder. Hence while teaching about
sleep hygiene, it is also important to counsel the elder
individual about lowering their expectations about
sleep duration.
c) Nutrition: By virtue of decreasing appetite and increasing
social isolation, elderly often have compromised
nutrition and imbalanced electrolytes. Minor changes
in blood levels of sodium, potassium, chloride, vitamin
D etc. could give rise to anxiety symptoms. Monitoring
through a simple nutrition chart, helps maintain basic
parameters, and at times is the only intervention
required to manage the anxiety.
2. Behaviour Therapy:
a) Relaxation Therapy: Classical Jacobson’s
technique of progressive muscle relaxation can
be taught to the individual with anxiety. This can
also be coupled with guided imagery, or practiced
alone.
b) Systemic desensitization : This works particularly
for phobias and unspecified fears for eg. fear of
falling. Creating a hierarchy and controlling the
response helps.
c) Exposure and Response Prevention: For OCD
d) Eye Movement Desensitisation and Reprocessing
(EMDR): For PTSD.

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3. Cognitive Therapy:
a) Cognitive Behaviour Therapy : The aim of CBT
in older adults is to target cognitive symptoms,
physical symptoms as well as behavioural symptoms.
First and foremost psycho-education is a must –
about the anxiety in general and management of
the same. Acceptance that the symptoms may not
be suggestive of a medical emergency, at the same
time being vigilant of associated co-morbidities,
becomes a tricky issue to deal with and require a lot
of awareness and self-monitoring . The principles of
relaxation and hierarchal construction may also be
used. The core of CBT, however, remains cognitive
restructuring using the ABC model(antecedents-
behaviour-consequences), wherein cognitive
errors and maladaptive behaviour are identified
and worked upon. The pace may have to be a little
slow, as with age new learning takes time, and
the template of old learned behaviours is hard to
change.
4. Mindfulness: Mindfulness as a therapeutic intervention
is finding applicability in a wide range of disorders.
Mindfulness is inculcating the ability to focus on ‘the
now’. It involves focussing initially on individual senses
for eg. taste, smell, vision, hearing etc. and then
graduating to focussing on one’s emotions, reactions,
responses etc. The aim is to harmonise the difference
between the mind and body. Mindfulness is particularly
important in the elderly, where there are so many
transitions taking place not only in the body, but also
in the mind, social interactions and roles within the
family as well as outside. All of these can contribute to
and worsen anxiety. Mindfulness then becomes a very
effective tool, under these circumstances.
5. Miscellaneous-
a) Yoga : Based on the medical condition of the
individual, various asanas can be taught. Yoga an
also be done sitting on a chair, and not on the
floor. More importantly relaxation, stretches and
pranayamas can be taught to senior citizens. There
is mounting evidence of control of elder anxiety
with Yoga.
b) Art Therapy: Free art in the form of drawing,
sketching or colouring as well as structured art
in the form of following instructions, are both
recommended. Art therapy can be planned as
an individual or group activity. Art is said to be
soothing and stimulates relaxation, which is
paradoxical to anxiety.
c) Dance therapy: Dance as a structured art form,
or free dance to music of one’s choice both
are advocated. Even for wheel chair bound and
individuals confined to bed, movement of the
upper body can help with some stimulation.
d) Music Therapy: Music as a form of environment
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modification has already been discussed. Music
can also be used as an activity—either singing
or playing an instrument. This can be done as
individual therapy or in a group, though there is
more evidence for group therapy.
e) Cognitive Rehabilitation: As much as the body
needs physical exercises, the mind too needs to
exercise itself. In our daily routine we do not even
realize how much we use the brain for planning,
sequencing and executing tasks. Cognitive
training involves activities like sorting by colour,
shape, sequence etc. It also involves memory
games wherein memorizing by loci, chunking,
pneumonics, visual imagery, su doku etc.
f) Social Activities or Networking : Interacting with
others not only is an important stimulus, but it
also improves synaptic connections between the
neurons in the brain. Social activity can be within
a small locus, or could be extended to external
activities like meeting in a senior citizen’s group,
laughter clubs, book clubs, ‘satsangs’ etc.
g) Alternative Therapies: Complementary and
alternative therapies like touch therapy,
reflexology, massage, reiki etc have been tried
with not very robust evidence. There are more of
anecdotal reports of the same.
While it is important to try out any of the above approaches,
one must not forget to keep in mind the caregivers dealing
with a patient of elder anxiety. Educating them about the
illness, expectations, response etc. are equally important in
the measure of overall response. Apart from information
related to the illness per se, it is vital that they learn the
art of communication, which can reduce the anxiety in the
elder individual. A few do’s and don’ts in this regard are:
Do’s
a) Talk in a neutral tone
b) Use very simple words and sentences. And speak slowly.
c) If instructing, please give one instruction at a time
d) If asking for something, please give maximally two
choices at a time
Don’ts
a) Use a harsh tone or voice
b) Use negative words or derogatory remarks
c) Lose your patience
Having a supportive and encouraging caregiver, is half the
battle won. A stay at home caregiver can even learn most of
the therapies by themselves, and minimize therapists visits.
However, if a trial of the above non-pharmacological
methods does not succeed, or the anxiety is too severe,
then pharmacological treatment can be initiated, but is
lowest possible doses for as short a duration as possible.
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Table 11: Treatment Overview

GAD PHOBIA PANIC DISORDER OCD PTSD
FIRST SSRI, SNRI, Buspirone SSRI, RIMA SSRI, SNRI SSRI SSRI
LINE
SECOND LINE Mirtazapine,,Pregabalin SNRI TCA TCA Mirtazapine
TCA,Tianeptine
THIRD BZD BZD, BZD, BZD BZD, Atypical
LINE MAO-I MAO-I antipsychotics

Table 12: Dosing strategies for commonly used Antidepressant Medications

Generic Name Starting dose Average Maximum recommended dose (CPS) Comments/Caution
mg/day Dose(mg)
SSRI
Escitalopram 5 10-20 20 mg Probably the safest in the elderly
Hyponatremia
Sertraline 25 50-150 200 mg Caution in those with bleeding
tendencies

SNRI
Venlafaxine 37.5 37.5-150 150 mg Watch for hypertension
Desvanlafaxine 50 50 50 mg Can start with 25 mg.
Watch for hyponatremia
Duloxetine 10 mg 10-30 30 mg Risk of falls
Others
Mirtazapine 15 30-45 45 mg Withdrawal is difficult
Pregabalin 75 150-600 600mg Very sensitive to side effects; giddiness
Use in caution with BZD
Tianeptine 12.5 12.5-50 50 mg Relatively free of side effects.
Well tolerated
Buspirone 10 10-60 60 mg Restlessness
TCA
Nortriptyline 10-25 40-100 200 mg Anti-cholinergic properties;
cardiovascular side-effects

Table 13. Common Side effects of medication seen in trial with an SNRI, and then the rest of the drugs follow.
elderly Benzodiazepines should be restricted to short term use,
Side Effect SSRI SNRI TCA Others and quickly tapered, owing to multiple problems that they
Hyponatremia   may lead to in the elderly.
Risk of bleeding  
QTc prolongation Occasional  While choosing a pharmacological agent, it is always
Narrow angle  preferable to follow the thumb rule—start low, go slow and
glaucoma
titrate upto usually half of the adult dose.
Anti-cholinergic 
effects
Elevated blood  Commonly, the following doses(Table 12) are recommended:
pressure
Giddiness   Pregabalin It is advisable to continue treatment for 4-12 weeks(longer
Serotonin syndrome if   for OCD and PTSD, before a response is expected). The
given in combination
Discontinuation Especially   Mirtazapine above can be combined with benzodiazepines, but with
syndrome Paroxetine use of both benzodiazepines as well as non-benzodiazepine
Toxicity in overdose  receptor agonists preferably should be limited to 2-4 weeks
Risk of falls Benzodiazepines in the initial period only. Both are associated with increased
Non-benzodiazepine
receptor agonists.
risk of falls, dissociative phenomena and confusion in the
elderly.

Pharmacological management Elderly in fact are quite sensitive to benzodiazepines, which

SSRI’s top the list of first line drugs(Table 11) across the have neuro-cognitive effects in them, similar to alcohol.
various disorders. Usually, failure of response leads to There use can also cause paradoxical agitation. Hence as far

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Fig. 1: Anxiety Disorder established

as possible we should avoid using them, but when required

use in very low doses and taper them quickly.

There are certain indications for benzodiazepines in

the elderly too-like alcohol withdrawal, pre-operative
anaesthesia, seizures and in very severe anxiety. However
here too, it is preferable to start with lower doses, and
quickly taper.
Fig. 2: Overview of approach to an elder individual with anxiety
or augment. The details of the same are discussed under
specific anxiety disorders.

Should there be no response with the first line of Other modalities of treatment
medications, then the second line can be tried either as Modalities of treatment like. rTMS, tDCS have been tried
monotherapy i.e switch to the given drug of another class in a few studies of anxiety disorders in adult patients, but

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Special issue
Medical Comorbidities
1. Heart disease
2. Chronic Obstructive
Pulmonary Disease
3. Parkinson’s disease(PD)
4. Endocrine disorders
5. Malignancy
Psychiatric Comorbidities
6. Comorbid depression:
7. Substance use disorders
8. Dementia
9. Agoraphobia
10. Complicated Grief
Other Issues of Importance
11. Fear of falls
12. Elder mistreatment
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Table 14: Issues of Special Concern.
Clinical presentation Management
Anxiety disorder following myocardial infarction is well known. Can effectively treated with escitalopram
Presence of anxiety and depression in heart disease increases the and sertraline (caution with those
morbidity and mortality in these patients. on anti-platelet agents), bupropion,
mirtazapine, duloxetine or venlafaxine,
desvenlafaxine, (In non responders and
in patients without conduction defects
and congestive cardiac failure).
In advanced stages COPD leads to a form of panic disorder precipitated In addition to anti-depressants psycho-
by exertion leading to a number of symptoms like avoidance of physical education, breath retraining and physical
activity for fear of getting a panic attack, fear of sudden death due to training are helpful.
asphyxia, guilt about chronic smoking and avoidance of social situations
due to negative body image.
40% of patients of Parkinson’s disease suffer from an anxiety disorder, SSRIs are effective with periodic
commonly GAD, Panic disorder, Social anxiety disorder, phobias or assessment for their side effects.
OCD. Depression is very commonly associated with anxiety disorders Buspirone may be another choice.
in Parkinson’s disease. Severity of PD, postural instability, gait Psychological interventions in the
disturbances, dyskinesia and young onset PD increase the risk. form of relaxation therapy, social skills
training and cognitive therapy are
effective in managing secondary anxiety.
Hypoglycaemia, hypo and hyperthyroidism, pheochromocytoma and Identifying and treating both the anxiety
hyperadrenocorticism are all associated with a high prevalence of anxiety disorder along with the endocrine
disorders. Anxiety disorders are also seen in Cushing’s disease, Carcinoid disease is the goal of management.
syndrome, hyperparathyroidism, hyperinsulinaemia, pancreatic tumours.
Quality of life of patients with malignancy deteriorates if the patient Treatment includes anti-anxiety drugs
develops anxiety as it creates many existential issues in the mind of and psychological interventions
the patient. These patients suffer from social isolation, pain, fatigue, including a spiritual component.
dissatisfaction in life. Anxiety and depression often coexist.
A high proportion of geriatric patients with anxiety disorders have Escitalopram and Nefazodone are found
coexistent depression leading to delayed acute treatment response and to be effective in depressed patients with
increased risk of relapse of depression with an increased risk of suicide. anxiety. The goal of treatment in these
patients is complete remission.
Anxiety disorders in elderly increase the risk of alcohol and medication Management includes a focus on age
abuse and vice versa. This leads to a poorer prognosis and outcome, specific issues such as loneliness,
increased mortality, increased suicidality and increased utilization of coping with loss, retirement, building
health services. self esteem and self efficacy, improving
social support and dealing with other
comorbid conditions like depression and
dementia.
Anxiety in dementia is associated with poorer quality of life, Psychosocial management along with
impairment in activities of daily living, sleep disturbances and poorer pharmacological management forms the
neuropsychological performance. mainstay of care.
There may be panic attacks leading to avoidance behaviour and limiting It is essential to be able to diagnose the
social activities. The main reasons for the panic attacks followed by underlying anxiety, so that it can be
agoraphobia are physical illnesses and traumatic events. treated.
It is distinct from depression and PTSD both, though it has many Psychosocial management is the
common features with both these disorders. Clinical features include mainstay of treatment. Clinical anxiety
shock, longing, disbelief, anger, guilt, intrusive memories, avoidance, and or depressive features may need
emotional numbing and feelings of loneliness. pharmacological management.
One may subsequently develop a phobia consisting of fear of further Implementing a rehabilitation programme
falls. This leads to functional impairment, reduction in activity level and following a fall e. g. Hip fracture,
decrease in social interactions. involving a mental health professional,
helps in prevention of this complication.
Depression, anxiety and PTSD are the commonest psychological Social support groups, skills training,
disorders occurring as a consequence of elder mistreatment. Female behaviour management and family
gender, poor self perceived health status, childhood trauma, neuroticism care conference are helpful in dealing
and intimate partner violence increase the risk of elder mistreatment. with elder mistreatment along with
appropriate pharmacotherapy for anxiety
disorders
Contd...
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Table 14: Contd..

Special issue Clinical presentation Management
13. Loneliness and social Being a female, being unmarried, low level of education, poor Educational groups, support groups,
isolation: socioeconomic status, poor self efficacy, mental illness, negative use of information and communication
life events and cognitive impairment predispose a person to develop technologies aimed at improving social
loneliness, which may be associated with anxiety. networks, of the lonely elderly are
shown to be successful interventions.
14. Hoarding It is more often in females who are single and living alone. When it Follow the management similar to OCD.
begins as a disorder of old age, it usually begins secondary to an illness
like dementia.

similar studies in elderly patients have not been done.
However rTMS has been shown to be useful in resistant
geriatric depression and it has been observed in these
patients that concurrent anxiety symptoms also improve.
Further research is needed in this area to establish these
treatment modalities in anxiety disorders.
Managing Side –effects
As the elder are more sensitive to side effects of most
medication, it is important for us to know of the common
side effects(Table 13) of the commonly prescribed anti-
anxiety medications, so we can keep a vigil on the same.
The overview below serves as a quick checklist.
There are two challenging side effects, commonly seen,
which are often difficult to deal with and manage. These are:
1] Hyponatremia
Hyponatremia is defined as a level of serum sodium below
135 mmol/l and is considered to be severe if it is below
120mmol/l. Usually below 130mmol/l would lead to nausea
and malaise and the elderly seem to be more prone to even
small changes in sodium levels. Below 115 mmol/l cn be life
threatening, leading to headache, disorientation, seizures,
coma, respiratory depression and even death.
In order to determine the cause, in addition to the sodium
levels, the total urine volume(24 hour) along with serum
and urine osmolality will give a clue. In addition tests of
thyroid and adrenal function may be done.
Once the cause is determined the approach is fairly standard:
- Remove the offending molecule if it is drug induced.
SSRI’s are notorious for causing the same in the elderly,
and along with correction, the offending molecule
should be replaced.
- Correct sodium levels by addition of sodium ( by
standard formulae for correction)
- Reduce total volume by fluid restriction, demeclocylcine,
vasopressin receptor antagonists etc.
2] Another very specific issue is managing benzodiazepine
abuse or dependence
Benzodiazepine Abuse is usually seen in two patterns
1. Non-medical or recreational abuse (to ‘feel good’)
2. Partial dependence due to quasi-therapeutic use -
long-term drug taking inconsistent with accepted
medicalpractice and at the same dose.
Benzodiazepine abuse may be approached in two steps:
A] Detoxification

Hyponatremia may be acute or chronic, or due to osmotic 1. Traditional Taper Method

demyelination. In chronic hyponatremia, there are increased
chances of falls due to two reasons-
a) Increase lethargy and confusion due to CNS impairment
b) Increased osteoclastic activity and decreased bone
mineralization leading to osteoporosis and frail bones,
which predispose to falls.
Hence it is important that hyponatremia is corrected at the
earliest. In order to correct it, one should ascertain whether
the hyponatremia is
i) Dilutional: a) Hypervolemic(oedema) secondary to heart
disease, nephritic syndrome, cirrhosis 2 mg daily, till 10 mg is reached. Then reduce by 1 mg daily
b) Euvolemic(no oedema) SIADH—which may be
idiopathic of drug induced; hypothyroidism, secondary
renal insufficiency
ii) Depletional : Secondary to volume loss—burns,
vomiting, trauma, diuretics, pancreatitis, primary
renal insufficiency.
Initially substitute with a longer acting BZD. Then start
tapering. Elder individuals may be sensitive to the side
effects and emergent paradoxical reactions with BZD, and
this becomes pronounced with longer acting molecules,
hence caution is advised.
The rule of thumb is 10% reduction till half the original dose
is reached, then 5% reduction till one-fourth the original
dose is reached, then 2.5 % reduction till 0.5 mg is reached
and then slowly increase the gap and gradually stop. For eg.
If 20 mg of diazepam is the substituted molecule, reduce by
till 5mg is reached. After this dose the next steps have to
be largely individualized. Then reduction can be by 0.5 mg
daily/alternate days/twice a week depending on the patient
response; till 0.5 mg is reached. Once 0.5 mg is reached
start increasing the gap between the doses i.e alternate
days, then thrice a week , then twice a week then stop.

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The response to tapering depends on
1. Individual patients
2. Setting-outpatient more difficult to monitor
3. Better if previous use was for therapeutic reasons
4. Co-morbid medications
5. Acceptance of need to abstain by the patient i.e patient
contract
2. Alternate method: Substitution to once daily dosing of
long acting BZD, taper over 4 weeks and stop.
B] Adjuvant pharamacotherapy-
In order to deal with the anticipated withdrawal syndrome,
anticonvulsants like Carbamazepine, Gabapentin, Valproic
acid may be used for about two weeks. In addition,
propranolol or anti-histaminics may also be tried for a
period of two weeks.
Treatment End Point
It is recommended that the duration of treatment should be
a minimum of 12 months starting from the time of remission
(and up to 2 years).
If the decision is made to stop medication, the dose should
be reduced over several months with monitoring for
relapse. Monitoring should be done 3-6 monthly keeping
two things in mind:
a) Remission/and or exacerbation of anxiety
b) Emergent cognitive symptoms
Specific Disorders
If we have to summarize the overall management and divide
it according to the various anxiety disorders in the elderly,
the following guideline may be useful(Fig.1):
Identify type of anxiety disorder
Based on type, review characteristics and initiate
management
Special Issues
Treatment of anxiety disorders in elderly is complicated
by comorbid psychiatric and medical conditions and
multiple medications that these patients may be
receiving. Certain medical illnesses in older individuals
require special mention, as may lead to anxiety
disorders(Table 14)
Conflict of Interest: Nil
BIBLIOGRAPHY
1. Gellis, Zvi D., and Stanley G. McCracken. 2008. “Advanced MSW
curriculum in mental health and aging.” CSWE Gero-Ed Center. Available
at www.gero-edcenter.org.
2. Ravi Soni, Demography and Epidemiology of Psychiatric Disorders in the
Elderly, Health and Medicine, Oct. 2nd, 2014 accessed from http://www.
slideshare.net
3. A Chowdhury, S Rasania. A Community Based Study Of Psychiatric
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Alka Subramanyam et al: Geriatric Anxiety Disorders
Disorders Among The Elderly Living In Delhi. The Internet Journal of
Health. 2007 Volume 7 Number 1.
4. Sreejith S. Nair, Pooja Raghunath, Sreekanth S. Nair; Prevalence of
Psychiatric Disorders among the Rural Geriatric Population: A Pilot
Study in Karnataka, India, Central Asian Journal of Global Health,
Vol.4, No.1(2015)
5. Elaine Kwan, Chanaka Wijeratne; Presentations of Anxiety in Older
People; Medicine Today 2016; 17(12): 34-41
6. Keri-Leigh Cassidy, MD; Neil A. Rector, PhD; The Silent
Geriatric Giant: Anxiety Disorders in Late Life, Geriatrics and
Aging. 2008;11(3):150-156
7. CANADIAN NETWORK For MOOD And ANXIETY TREATMENTS
(CANMAT.ORG)
8. Beattie E., Pachana N., Franklin S.(2010). Double Jeopardy: Comorbid
Anxiety and Depression in Late Life. Research in Gerontological Nursing.
3(3) 209-220.
9. Bonnie S. Wiese, Geriatric depression: The use of antidepressants in the
elderly. BCMJ, Vol. 53, No. 7, September, 2011, page(s) 341-347.
10. Campanelli, C. M. (2012). American Geriatrics Society Updated Beers
Criteria for Potentially Inappropriate Medication Use in Older Adults: The
American Geriatrics Society 2012 Beers Criteria Update Expert Panel.
Journal of the American Geriatrics Society, 60(4), 616–631.
11. Singh S, Sarkar S. Benzodiazepine abuse among the elderly. J Geriatr
Ment Health 2016 -3:123-30. 12. Diefenbach, G. J., & Goethe, J.
(2006). Clinical Interventions for Late-Life Anxious Depression. Clinical
Interventions in Aging, 1(1), 41–50.
13. Soiza RL and Hannah S.C. Talbot Management of hyponatraemia in older
people: old threats and new opportunities Ther Adv Drug Saf (2011) 2(1)
9_17
14. Bleakley S. The pharmacological management of anxiety disorders
Progress in Neurology and Psychiatry 15-20. Accessed through www.
progressnp.com
15. Orgeta V, Qazi A, Spector AE, Orrell M. Psychological treatments for
depression and anxiety in dementia andmild cognitive impairment.
Cochrane Database of Systematic Reviews 2014, Issue 1.
16. Olthuis JV, Watt MC, Bailey K, Hayden JA, Stewart SH. Therapist-
supported Internet cognitive behavioural therapy for anxiety disorders in
adults. Cochrane Database of Systematic Reviews 2016, Issue 3.
17. LenzeEric J, Wetherell Julie Loebach Anxiety disorders, in Textbook of
Geriatric Psychiatry ed Blazer Dan G., Steffens David C. 4th edition, The
American Psychiatic Publishing, p. 333-345.
18. Wetherell Julie Loebach, Stein Murray B, Anxiety disorders in
chapter Geriatric Psychiatry in Kaplan and Sadock’s Comprehensive
Textbook of Psychiatry,ed Sadock Benjamin, Sadock Virginia, Ruiz
Pedro, 9 th Edition, Wolters Kluwer, Lippincott Williams & Wilkins,
p. 4040-4047.
19. Katzman Martin A, Bleau Pierre, Chokka Pratap et al, Canadian Clinical
Practice guidelines for the management of anxiety, posttraumatic
stress and obsessive compulsive disorders, BMC Psychiatry, 2014,
14(suppl 1),S1.
20. Stojanovic J, Collamati A, Mariusz D et al. Decreasing Loneliness and
social isolation among the older people: systematic research and narrative
review. Epi Biostat and Pub Health. 2017; 14(2), Suupl. 1, e12408-1 –
e12408-8.
21. Dong Xin Qi, Chen RuiJia, Chang E-Shien et al. Elder abuse and
psychological well being: A systematic review and implications for
research and policy- a mini review. Gerontology.2013; 59:132-142.
22. Dong Xin Qi. Elder abuse: a systematic review and implications for
practice. JAGS. 2015. 63: 1214-1238.
23. Schuurmans J, Balkom A. Late life anxiety disorders: a review. Curr
Psychiatry Rep. 2011; 13(4): 267-73.
24. Tampi R, Tampi D. Anxiety disorders in late life: A comprehensive review.
Healthy aging Research. 2014; 3:14
25. Walsh K, Bennett G. Parkinson’s disease and anxiety. Postgrad Med J.
2001, 77: 89-93.
26. Wison K, Chochinov H, Skirko G. Depression and anxiety disorders in
palliative cancer care. J pain and Symp Management. 2007; 33(2),
118-129.
27. Hall R, Hall R. Anxiety and endocrine disease. Semin in clin
neuropsychiatry. 1999; 4(2): 72-83
28. Ascott- Evans B, Kinvig T. Endocrine disorders in the elderly. Endo Dis.
2004; 22(11): 623-628.
29. Dissananyaka N Sellbach A, Matheson S. Anxiety disorders in
Parkinson’s disease: Prevalence and risk factors. Mov Dis. 201; 25(7):
838-845.
30. O’Hara, Beaudreau, Late-Life Anxiety and Cognitive Impairment: A Review
Am J Geriatr Psychiatry 16:10, October 2008
31. Chattopadhyay K, Singh AP. Anxiety and its impact on quality of life
among urban elderly population in India:An exploratory study. Indian J
Res Homoeopathy 2016;10:133-41.
S381
[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]
Alka Subramanyam et al: Geriatric Anxiety Disorders
32. Syed Elias SM, Neville CC, Scott TL, The effectiveness of group
reminiscence therapy for loneliness, anxiety and depression
in older adults in long-term care: Asystematic review Geriatric
Nursing (2015) 1-9
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Clinical Practice Guideline for Management of Psychoses in Elderly
Shiv Gautam, Akhilesh Jain1, Manaswi Gautam, Anita Gautam
Director Professor, Gautam Hospital & Research Center, Jaipur, Consultant Psychiatrist Gautam Hospital and Research
Center, 1Specialist Psychiatry ESI Hospital, Correspondence: dr_shivgautam@yahoo.com
Other Expert participants: K K Verma, Debjani
Bandyopadhayay, G Prasad Rao, Om Prakash Singh Jhirwal
INTRODUCTION
According to Statistics of India in April 2016 population of people
above the age of 60 years has increased to 8.6 % of 121 Crores.
Age related changes in the Central Nervous System commonly
seen in the process of ageing include, Gross brain atrophy,
Ventricular enlargement, Selective regional neuronal loss,
Remodeling of dendrite, axons and synapses, Appearance
of intraneuronal lipofuscin, Selective regional decrease in
neurotransmitter and neuropeptides, Selective modification
of neurotransmitter metabolism, Possible dysregulation
of gaseous neurotransmitter metabolism, Glucocorticoid
neurotoxicity, Changes in receptors, Changes in neurotrophins,
Changes in signal transduction, Impairment of calcium
homeostasis, Possible changes in cell cycle regulations (eg,
cyclins), Possible changes in extra cellular matrix proteins (eg.
Laminin, proteoglycans), Possible regional decline in cerebral
blood flow, Possible regional decline in metabolic rate and
Appearance of senile plaque & neurofibrillary tangles.
PHARMACOKINETIC CHANGES WITH AGING
When we look at pharmacodynamics with aging changes
are seen in Neurotransmitter Pharmacodynamics,
Dopaminergic system, Dopamine D2 receptor in the
striatum, Cholinergic system, Choline acetyl transferase,
Cholinergic cell numbers and in Adrenargic system changes
are seen in cAMP production in response to beta-agonists,
Beta – adrenoceptor number, Beta – receptor affinity and
Alpha 2 – adrenoceptor responsiveness.
Changes in Gabaminergic system show effect on
Psychomotor performance in response to benzodiazepines
due to Post – synaptic receptor response to GABA.
Table1: INDIA AGEING
Population 121 crore Women 58.76 crore
Over 60 10.39 crore Over 60 5.28 crore
% share 8.6% % share 9%
Men 62.3 crore Over 60 in 2001 7.6 crore
Over 60 5.11 crore Over 60 in 2011 10.3 crore
% share 8.2% % increase 35.5%
© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
Psychosis is characterised by loss of contact with reality.
DSM -5 defines it by presence of delusions, hallucinations,
disorganized thinking (speech), grossly disorganized or
abnormal motor behavior including catatonia or negative
symptoms. In older populations its etiology, manifestations
and treatment deserved special consideration. Psychosis in
elderly includes schizophrenia, delusional disorders, psychotic
depression, schizo affective disorders, psychotic behavior
associated with dementia including Alzheimer disease,
parkinsons disease, lewy body and vascular dementias.
Commonest among psychoses is schizophrenia which occurs
in early age (late second and early third decade of life). In
contrast to early onset schizophrenia its presentation after
the age of 40 is called late onset schizophrenia and that after
the age of 60 is known as very late onset schizophrenia.
CHARACTERISTIC FEATURES OF VERY- LATE
ONSET SCHIZOPHRENIA
Females show significantly higher number than males.
Compared with early- or late-onset schizophrenia, very-late-
onset schizophrenia is characterized by associated sensory
impairment, Social isolation, greater likelihood of visual
hallucinations, lesser likelihood of formal thought disorder
and affective blunting, lesser likelihood of family history of
schizophrenia, greater risk of developing tardive dyskinesia.
DRUG-INDUCED PSYCHOSIS
Due to process of ageing Elderly patients are suffering from
other physical illnesses and often receive multiple medications.
Drugs that can produce psychotic symptoms in elderly patients
and drug interactions and dosage must be considered when
evaluating drugs as causative agents of psychotic symptoms.
Table 2. Pharmacokinetic Changes with Aging
Absorption Metabolism
↑ Gastric pH ↓ Hepatic mass
↓ (Delayed) gastric emptying ↓ Hepatic blood flow
↓ Splanchnic blood flow ↓ Phase I Metabolism
↓ Intestinal motility (unchanged) phase II metabolism
Distribution Elimination
↑ Body Fat ↓ Creatinine clearance
↓ Total body water ↓ Glomerular filtration rate
↓ Albumin ↓ Tubular secretion
↑ Alpha1 acid glycoprotein ↓ Creatinine production
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Shiv Gautam et al: Management of Psychoses in Elderly

Table:- 3 Clinical Features and Epidemiology of Table 4: Characteristics of common causes of psychosis
psychoses in old age
Disorder Clinical features Characteristic Delirium BPSD Late Onset
Late onset Life time Prevalence of early onset schizophrenia is 1.0% Features psychosis
Schizophrenia while that of LOS and VLOS is 0.3%. In comparison to Onset Acute gradual Acute/gradual
40 to 60 years EOS, patients with LOS and VLOS more commonly have Course Flactuating Stable/ Stable/progressive
Very late onset visual, olfactory, and tactile hallucinations, and may be progressive
schizophrenia more likely to have persecutory and partition delusions. Duration Hours to days Months to years Months to years
> 60 years Positive symptoms may be less severe in LOS and VLOS. Sensorium flactuating Clear until Clear
Delusional Delusional disorders are less common, their life time progressed
disorder prevalence is reported to be 0.18%. Characterised by Psychomotor Increased / Usually normal Usually normal
Presence of at least one delusion for at least one month in activities unpredictable
the absence of functional impairment or bizarre behavior. Cognitive functions Grossly impaired Not much
Psychotic MDD is seen with the presence of psychotic features, impaired impaired
depression which are usually mood congruent, late-onset psychotic Hallucination Predominantly Commonly Visual, Olfactory
depression tends to involve more severe depression, visual Visual or tactile
greater psychic anxiety and symptoms of hypochondriasis, Typical delusions fleeting Non Bizarre Complex/bizarre
increased frequency of somatic delusions, but fewer Misidentification of - frequently rarely
delusions of guilt and paranoia. Lifetime prevalence of caregivers
Depression with psychotic features has been reported to Past history of rare rare common
be 0.35%. psychosis
Schizoaffective Life time prevalence of SAD has been reported to be Eventual recovery frequent frequent uncommon
Disorder 0.32%. Characterised by depressed or manic episode from psychosis
in the presence of an uninterrupted psychotic illness, Length of Brief Brief Long term
additionally psychotic features must be present for at least maintenance on
a two-week period in the absence of mood features. antipsychotic
Bipolar In elderly very late onset, BPAD is estimated between medication
disorder 0.25 to1 %.Studies are limited and conflicting. Increased
depressive episodes with psychotic features in one study
and no difference in another. High prevalence of thought Table:- 5 Similarities and differences between early- and
disorders in elderly and high rate of aggression and late-onset / very late-onset schizophrenia
irritability in early onset and younger adults Similarities Differences
Delirium Constitutes about 10% of all causes of psychoses in elderly.
• Both have Genetic risk LOS / VLOS schizophrenia is
Prevalence rate is as high as 50% in hospitalized elderly
• The positive symptoms are characterized by:
patients in ICU. Perceptual disturbances are more common.
severe in both groups. • Fewer negative symptoms
Psychoses is more commonly reported in hyper active variant.
• Psychosocial maladjustments • Better neuropsychological performance
Alzheimer’s Patients with Alzheimer’s disease have associated
are seen in early course of • Better response to antipsychotics
disease psychotic features which include visual Hallucinations
illness.
and delusions which tend to be simple and non-complex
• Brain abnormalities revealed by
delusions, most commonly involve the misidentification
imaging are similar.
of people and paranoid delusions. The most common
delusions are ones of theft or property being taken away by
others. Prevalence of psychotic symptoms in Alzheimer’s Table 6: Medications used for other physical illnesses
disease have been reported about 41%. which are Associated With Psychotic Symptoms in the
Parkinson’s Psychotic symptoms in PD commonly seen include
disease Stereotyped and non frightening visual hallucinations,
Elderly
delusions are less common and tend to be paranoid Anticholinergics and Diphenhydramine, Hydroxyzine, Cimetidine
and non-bizarre. Prevalence of psychotic symptoms in antihistamines
Parkinson’s Parkinson’s disease has been reported to be 43%. Analgesics and anti- Indomethacin and Aspirin (acetylsalicylic acid)
disease Prevalence of visual hallucinations in Parkinson’s disease inflammatory drugs
Dementia dementia has been reported to be 89%. Antineoplastic drugs Prednisone
Lewy body In LBD Visual hallucinations are common and tend to occur Anti parkinsonian drugs Levodopa or carbidopa, Amantadine,
dementia early in the disease course, the visual hallucinations tend to be and related compounds Bromocriptine and Procyclidine
well formed and non frightening, as in Parkinson’s disease. Antidepressants Tricyclic antidepressants: Amitriptyline,
Tends to occur within one year after the onset. Prevalence of Imipramine, Doxepin
Psychotic symptoms reported include hallucinations (78%), Selective serotonin reuptake inhibitors:
misidentifications (56%) and delusions (25%) Fluoxetine, Sertraline, Paroxetine
Vascular Variable estimates of psychotic symptoms have been reported. Bupropion and Venlafaxine
dementia Anticonvulsants Phenytoin, Primidone and carbamezapine
Conventional Chlorpromazine, Thioridazine, Haloperidol
antipsychotics
FACTORS CONTRIBUTING TO INCREASED Benzodiazepines, Alcohol Methylphenidate, Amphetamine, Ephedrine
RISK OF PSYCHOSIS IN ELDERLY and Stimulants
Antiarrhythmic Digoxine, Propranolol, Quinidine and
Factors which contribute to increased risk of developing Procainamide
Other drugs Corticosteroids, Interferon
psychotic symptoms in old age include age-related

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deterioration of frontal and temporal cortices,
pharmacokinetic and pharmacodynamic changes,
Neurochemical changes, Social isolation, Sensory deficits,
Cognitive decline and Polypharmacy.
ASSESSMENT AND EVALUATION
Systematic observation of the patient with concentration
on the following areas:
• Assess symptoms to identify the problem.
• Assess antecedents and consequences
• Clarify negative effect of the symptoms on the patient
and caregivers because psychotic symptoms that do not
have a negative impact may not require treatment.
• Ascertain possible causes for the symptoms e.g.
environmental causes.
• Whether the patient has a negative view of the caregiver
or inability to understand the intentions of caregivers.
• Whether the patient suffers from social isolation or
sensory deprivation.
• Whether the patient misinterprets the environment
and situations.
Diagnostic criteria for schizophrenia (adapted from DSM-
IV-TR)
Characteristic symptoms
2 (or more) of the following, each present for a significant
portion of time
during a 1-month period (or less if successfully treated):
(1) delusions
(2) hallucinations
(3) disorganised speech, eg frequent derailment or
incoherence
(4) grossly disorganised or catatonic behaviour
(5) negative symptoms, ie affective flattening, alogia, or
avolition
SOCIAL/OCCUPATIONAL DYSFUNCTION
Duration: continuous signs of the disturbance persist for at
least 6 months
Exclusion of schizoaffective and mood disorder
Exclusion of substance/general medical condition
Agitation: The term agitation refers to a range of behavioral
disturbances including aggression, combativeness, shouting,
hyperactivity and disinhibition .The most common cause of
agitation in old age is delirium followed by dementia. Other
conditions like Schizophenia,BPAD,Psychotic Depression
may also cause agitation in this age group.
Preventive Interventions
Reorientation should be ensured by familier person and optimal
level of sensory input.Loud noise should be avoided and patient
should be allowed to have adequate and uninterrupted sleep.
Hydration should be maintained either orally or intra venously.
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Shiv Gautam et al: Management of Psychoses in Elderly
Physical restrainment should be discouraged as it may further
escalate the agitation. The use of unnecessary medications
should be avoided. The management strategy should follow
the basic principles as outlined before
Pharmacological Interventions
If agitation is severe enough to render patient himself or
others in danger, rapid sedation is necessary. Pharmacologic
options include the benzodiazepines and the typical and
atypical antipsychotics agents. Intravenous, intramuscular
or oral route may be preferred considering the level of
agitation and associated physical condition of the patient
Summary of the Initial Evaluation and Management of the
Agitated Elderly Patient
· Provide immediate interventions for urgent medical
conditions
· Assume the etiology of the agitation is delirium
· Assess for underlying etiology or exacerbating factors
and manage appropriately
· Review history of present illness, medical history and
medication profile
· Provide optimal environmental and supportive
interventions
· Pharmacological agents should be considered when the
patient has the potential to harm themselves or others,
or is impeding medical evaluation and management
· Dose must be adjusted considering age of the patient
DELUSIONAL DISORDER
Prevalence of Delusional disorder have been reported 0.03% of
elderly population. Delusional disorder may account for 1- 4
% in admitted elderly population. Delusional parasitosis tend
to occur more frequently specially in females. To establish
the diagnoses of delusional disorder, clinician must rule out
the possibility delirium, dementia, psychotic disorders due to
general medical conditions or substance use, schizophrenia,
mood disorders with psychotic features, significant organic brain
syndrome or physical illnesses like pellagra. These patients may
be treated with risperidone, olanzapine, quetiapine. Treatment
should be started at low dose and gradually be titrated upward.
CHARACTERISTIC SYMPTOMS OF
DELUSIONAL DISORDER
Non bizarre delusions, ie involving situations that occur in
real life, such as being followed, poisoned, infected, loved at
a distance, or deceived by spouse or lover, or giving a disease)
of at least 1 month’s duration, Not meeting the criteria for
schizophrenia, No marked social or occupational dysfunction,
Exclusion of mood disorder, Exclusion of substance abuse.
Subtypes:
Erotomanic type: delusions that another person, usually of
higher status, is in love with the individual .
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Shiv Gautam et al: Management of Psychoses in Elderly
Grandiose type: delusions of inflated worth, power,
knowledge, identity, or special relationship to a deity or
famous person .
Infidelity type: delusions that the individual’s sexual partner
is unfaithful
Persecutory type: delusions that the person (or someone to
whom the person is close) is being malevolently treated in
some way
Somatic type: delusions that the person has some physical
defect or general medical condition Mixed type: delusions
characteristic of more than 1 of the above types but no 1
theme predominates
BIPOLAR AFFECTIVE DISORDER
In elderly very late onset ,BPAD is estimated between
0.25 to1 %.Studies are limited and conflicting. Increased
depressive episodes with psychotic features in one study
and no difference in another. High prevalence of thought
disorders in elderly and high rate of aggression and
irritability in early onset and younger adults.
Drug treatment advised is atypical antipsychotics except
clozapine. Olanzapine-Fluoxetine combination has strong
evidence in mixed bipolar patients.
PSYCHOTIC DEPRESSION
Late onset depression(>60 Yr) is more commonly associated
with delusion than the early onset. Delusion of persecution is
more common in this age group. Nilhistic delusion may also
occur more commonly but hallucinations are less common.
Pharmacological treatment includes use of SSRI (Citalopram,
escitalopram, fluoxetine, paroxetine, and Sertraline).
Tricyclic antidepressant can be tried in those patients
who have not responded to SSRI and can tolerate the
side effects. In severe cases ECT continues to be the most
effective treatment.
Diagnosis of Late-Life Psychoses
Late life Psychoses caused by a psychiatric disorder is called
primary and that due to a medical or neurological disorder
is considered secondary. About three fifths of psychotic
disorders in later life are due to a secondary condition.
Delirium, Drugs, alcohol, toxins, Depression and other
affective disorders are most commonly associated with late life
psychoses, Dementia, Delusional disorder and schizophrenia
spectrum disorder are main stay of the diagnostic categories.
Clinical presentations commonly seen which raised suspicion
of secondary causes of psychosis are as follows:-
• Late age of onset of the presenting psychiatric symptoms
• Family history and past history of mental illness less
commonly observed.
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• Severity of symptoms more than expected
• Abrupt personality change followed by psychopathology
• Comorbid medical conditions.
• Abnormalities of cognition like memory and
consciousness
• Low response to psychiatric treatment
PLANNING INTERVENTION
The following points should be kept in mind:
• Needs of the particular patient and the cause of the
symptoms.
• Where is the intervention required? Patient or at the
environment or members of staff or the general system
of care.
• Regular assessment and re-evaluation of the intervention
is required to monitor improvement
FORMULATING A TREATMENT PLAN
Points to remember before prescribing medication in elderly
Magnitude of effect (clinical response) = Pharmacodynamics
(potency of a drug for binding to the receptor) x
Pharmacokinetics (drug concentration at the site of action
x biological variance (individual biology of he patient and
targeted disease process.
• In elderly medical complication of pharmacotherapy alone
constitute a highly significant treatable health problem.
• Adverse reaction to drugs of all types is seven times
higher in those aged 70 to 79 years, than in those 20 to
29 years old.
• Non compliance with therapy is a major problem for
psychiatric patients, and this dilemma is exacerbated
with age.
• Age related health problems combines with physiological
changes to increase the probability of adverse effect from
medication which in turn increase the likelihood of non
compliance.
• Complexities of medication regimens are further complicated
by communication difficulties arising from impaired hearing,
cognitive impairment, language & cultural difficulties.
MANAGEMENT
• Pharmacological
• Psychosocial interventions
Step 1.
Rule out organic and environmental causes of psychotic
symptoms e.g. deafness, poor vision, chronic pain,
dehydration, deranged metabolic functions and constipation,
medications that can cause/aggravate psychotic.
Step 2.
Decide whether the symptoms are causing distress or
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Shiv Gautam et al: Management of Psychoses in Elderly

disruption in the patient’s life to warrant treatment with Table:- 7

antipsychotic medication, carefully evaluate potential risks Disorder Drug of Dose range Side Effects
due to side-effects and benefits of symptom relief with the use choice per day
of antipsychotics. A common example is of an older lady with LOS/ Quetiapine 100 -300 mg Hypotension,QTC changes,weight
chronic schizophrenia presenting with musical hallucinations VLOS gain,sedation
that are not distressing. A simple social intervention such as
Olanzapine .5-15 mg Weight gain,metabolic
organising day care to reduce her loneliness or provision of a syndrome,hypotension
hearing aid may solve the problem as compared to starting/
increasing the dose of antipsychotics. Risperidone 1.5 to 3.5mg EPS,sedation,sedation

TREATMENT OF LATE ONSET SCHIZOPHRENIA Aripeprazole 15-30mg less likely to cause extra pyramidal
symptoms, sedation, weight gain
and cardiovascular side-effects
Conventional antipsychotics
Significant improvement in psychotic symptoms with the Clozapine Up to 50 mg Seizures,haematological,anticholi
use of haloperidol and trifluoperazine (10-30mg a day) were nergic,
sedation,weight gain
reported in the 1960’s.
Delusional Risperidone 1-2.5mg EPS,sedation,sedation
Depot antipsychotics can be useful in older patients with disorder
compliance problems. Use of low doses of depot antipsychotics Olanzapine 5-10 mg Weight gain,metabolic
such as flupentixol decanoate or fluphenazine decanoate syndrome,hypotension
every two weeks can produce a better clinical outcome.
Quetiapine 50-200mg Hypotension,QTC changes,weight
gain,sedation
One of the common dilemmas encountered in clinical
practice is the management of an older patient with chronic BPAD Risperidone 1-2.5mg EPS, sedation, sedation
schizophrenia who has been stable on a depot for a number
Olanzapine 5-10 mg Weight gain, metabolic syndrome,
of years but has now started to develop extra pyramidal hypotension
symptoms. There is usually an associated element of
cognitive and functional decline. The first step is to review Quetiapine 50-200mg Hypotension, QTC changes, weight
the dose of depot medication as older people do not need gain, sedation
higher doses and can easily be managed on a smaller dose
Psychotic Escitalopram 5-10 mg GI disturbance,
as discussed above. The second step Depression Dry Mouth,
fluoxetine 10 – 20 mg Rest less ness,
would be to either consider using a small dose of paroxetine 12.5 – 25mg insomnia,
anticholinergic medication such as procyclidine or consider Sertraline 25– 50 mg headache,
sexual dysfunction
using an atypical antipsychotic in oral or depot form – only
risperidone depot (Risperdal Consta) is available. Olanzapine 5-10 mg Weight gain, metabolic syndrome,
hypotension
The clinical decision-making process would involve weighing
these options against the risk of relapse, severity of illness Quetiapine Hypotension,QTC changes,weight
50-200mg
gain,sedation
and the overall quality of life of the individual patient.
Aripeprazole less likely to cause extra pyramidal
Atypical antipsychotics 15-30mg symptoms, sedation, weight gain
The first choice treatment for older patients now considered and cardiovascular side-effects
to be safe and effective are atypical antipsychotics due Dementia Risperidone 0.25-1.5mg EPS,sedation,sedation
with
to their better side-effect profile in comparison with BPSD Olanzapine 2.5-10 mg Weight gain,metabolic
conventional antipsychotics. syndrome,hypotension

Risperidone Quetiapine 12.5-200mg Hypotension,QTC changes,weight

The most extensively studied atypical antipsychotic in the
older population is risperidone. It is effective as a first-line
antipsychotic agent, is well tolerated in lower doses (1.5-
6mg daily) and produces significant clinical improvement in
older patients with schizophrenia.
Olanzapine
Olanzapine is claimed to significantly improve symptoms
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
gain,sedation
Aripeprazole 2.5-12.5 mg less likely to cause extra pyramidal
symptoms, sedation, weight gain
and cardiovascular side-effects
of schizophrenia and extra pyramidal side effects. However
the data available on the use of olanzapine in older patients
population of schizophrenia are limited.
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Shiv Gautam et al: Management of Psychoses in Elderly
Quetiapine
Quetiapine has been reported to be safe in older people
though the data available are limited. It has been reported
to be safely used in doses up to 750mg daily in divided doses
with a warning that in order to avoid potential side-effects
like postural hypotension and dizziness, it was better to
start at a lower dose and titrate slowly upwards.
Aripiprazole
Aripiprazole is less likely to cause extra pyramidal
symptoms, sedation, weight gain and cardiovascular side-
effects. However, there is a paucity of data on its use,
safety and dosing strategies in older people. It has been
reported to improve both positive and negative symptoms
and caused fewer side-effects. Dosing regimens should be
tailored according to the needs of individual patients. It is
the latest of the atypical antipsychotics with a unique mode
of action of being a partial agonist at D2 receptors.
Clozapine
The usefulness of clozapine in treatment-resistant early cases
is well established, but concerns about toxicity and the need
for monitoring white cell counts has led to a limited use in
older patients. In a review of clozapine use in older psychiatric
patients, the authors concluded that most patients showed
moderate to marked improvement of psychotic features at
a relatively low mean dose of 134mg per day, and cautioned
that agranulocytosis may occur more frequently in older
patients. In view the above-mentioned risks, clozapine is not
a first-choice antipsychotic for older patients and should only
be used in cases of treatment resistance and severe TD.
NON- PHARMACOLOGICAL MANAGEMENT
Electroconvulsive therapy
It appears that with the introduction of a variety of typical
and atypical antipsychotics, the use of ECT in older patients
with schizophrenia has declined in clinical practice. A better
response to ECT in patients of late paraphrenia presenting
with dominant affective symptoms has been reported.
Psycho-education
Depending upon the diagnosis of the patient psycho-education
has to be provided to the patient and the care givers regarding
disease, its causes, likely course of illness, treatment options
and selection of treatment with its rationale and an emphasis
on regularity of treatment, follow up care.
Cognitive behavioural therapy
Cognitive behavioural techniques aiming at modification
of delusional beliefs and control over hallucinations has
been widely reported. Unfortunately there have been few
research studies conducted on the use of these techniques
in older patients. The possibility of their use in helping
older patients gain insight into their illness and address
coping strategies to help them live a meaningful life.
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In 2000 a novel approach of an integrated cognitive
behavioural and social skills training intervention for older
people with schizophrenia was developed. This treatment
approach suits the needs of older patients and aims to
reduce their cognitive vulnerabilities, improving abilities to
cope with stress and adherence to other forms of treatment.
Psychosocial therapies
Psychosocial interventions aimed at improving independent
living and social skills is well established. Such interventions may
be of importance in older patients as a significant number fail
to show a complete response to antipsychotics. A combination
of interpersonal and independent skills training, along with the
standard occupational therapy, has been found to be associated
with improved social functioning and independent living.
Choice of treatment settings
Treatment setting includes management in indoor setting
followed by treatment in the OPD. Since the psychotic illness in
elderly needs adequate evaluation, assessment and management,
indoor treatment should be preferred. General ward with other
psychotic patients is not advisable. Patients should be given
individualized care preferably in a single room with least
sensory stimulation and intensive nursing care. It is advisable to
keep close care givers with the patient with an advise to keep the
patient oriented to time, day, date and place. In case of medical
comorbidity physician on call should be readily available.
Management of maintenance phase
Appropriate reduction in the doses of the drugs given
during acute phase and considering the improvement in the
patients clinical status should be made and first onset late
psychoses should be treated for at least one year. Treatment
may be continued longer in case of relapse of the illness.
When to stop treatment
As a rule, medication should be started at the low dose with
gradual upward titration until the clinical response is observed.
Once the optimal response is achieved, the same effective dose
should be continued for another 2 to 4 months with subsequent
gradual tapering and maintenance treatment as advised.
Optimal duration of treatment with antipsychotic
medications largely depends upon residual clinical picture
and psychosocial context of the patients and clinical
judgment of treating psychiatrist.
Special issues
Medical comorbidities
Secondary conditions are responsible for about three fifth
of psychotic disorders in elderly. Hence, a very careful and
comprehensive examination including history, physical
and neurological evaluation remains crucial for accurate
diagnoses and treatment.
Treatment in such cases should be based on underlying
medical condition. First line of treatment must focus on
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Shiv Gautam et al: Management of Psychoses in Elderly

behavioral and environmental strategies, however use of in to consideration while evaluating and treating psychoses
antipsychotics is indicated in case of symptom severity. in older adults.
Treatment should be tailored according to patients need
and should be time limited and dose limited. Metabolic conditions associated with psychoses include Vitamin
B12 deficiency, Folate deficiency, Electrolyte abnormalities,
It is advisable to avoid clozapine, olanzapine and Sodium, Potassium, Calcium, Magnesium, Acute intermittent
conventional antipsychotics in patients with major porphyria, Hepatic encephalopathy, Uremic encephalopathy,
metabolic conditions like diabetes, dyslipidemia, obesity Other nutritional deficiencies, Anoxia/hypoxia, Hypercarbia,
etc. similarly in cardiac patients clozapine, ziprasidone Infections, Meningitides, Encephalitides (e.g., herpes,
and conventional antipsychotic should be avoided. It is etc.), Neurosyphilis, HIV/AIDS, Pneumonia, Neurological,
preferable to use risperidone and quetiapine in such cases. Parkinson’s disease, Epilepsy, Temporal lobe epilepsy, Grand
mal, Non-convulsive status epilepticus, Subdural hematoma,
Common Comorbid medical causes of psychosis in elderly Cerebrovascular events, Huntington’s disease, Multiple sclerosis,
persons have been mentioned below which should be taken Amyotrophic lateral sclerosis, Tumors, Temporal lobe—auditory
hallucinations, Occipital lobe—visual hallucinations, Limbic—
Table:- 8
delusions, Hypothalamus—delusions, Limbic encephalitides,
During Intoxication During Withdrawal
Autoimmunereference, Paraneoplastic syndromes, Systemic
Alcohol Alcohol lupus erythematosis, Vasculitides, Sleep disorders (narcolepsy),
Cannabis Sedatives, hypnotics, or anxiolytics
Other genetic/heritable conditions, Likely to have been diagnosed
Phencyclidine Other substances
Other hallucinogens in childhood, Endocrine, Hypo-/hyperthyroidism, Adrenal
Inhalants disease, Hypo-/hypoglycemia and Hypo-/hyperparathyroidism
Sedatives, hypnotics, or anxiolytics
Stimulants (inclusive of amphetamine- Psychiatric comorbidities
type substances, cocaine, or other Common psychiatric comorbidities observed with psychoses
unspecified stimulants) & Other in elderly include depression, dementia, delirium, delusional
substances
disorder, anxiety/ agitation, which needs to be addressed after
ruling out possible secondary causes if any (medical disorders/
electrolyte/ metabolic disturbances, drugs). Management of co
morbidity has to be planned primarily by non pharmacological
management and medication if unavoidable.

Substance dependence
Multiple substances have been implicated in causation of
psychoses in elderly population either during intoxication
or withdrawal.

First line of treatment in such cases should focus on

withdrawal of offending substance, appropriate treatment
of non psychotic withdrawal symptoms and management
of psychotic symptoms with appropriate antipsychotic in
half the adult dose. Psychosocial interventions like CBT,
Motivational enhancement therapy should be encouraged
at the clearance of cognitive symptoms if any.

Risk of Suicide
Person aged 75 years or above have higher suicide
rates among all age group. Suicide attempts in elderly
population are often long planned and involves more lethal
methods as compared to younger counterparts who often
have communicative act and impulsive attempts. Major
depression is the most common cause in this population
who attempt or complete the suicide. Primary psychotic
disorders including schizophrenia, schizoaffective illness,
and delusion disorder, as well as anxiety disorders, tend to
be present in lower proportions. Physical illness also plays a
significant role in suicidal behavior in this population.

Key Risk factors

PSYCHOSES IN ELDERLY – ALGORITHM OF TREATMENT · Recent Stressful life events

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Shiv Gautam et al: Management of Psychoses in Elderly
· Presence of chronic/terminal illness with diaability
· Recent bereavement or relationship breakdown
· Widow/widower
· Evidence of depression /loss of interest or losas of pleasure
· Evidence of withdrawal
· Warning of suicidal intent
· Evidence of a plan to commit suicide
· History of psychosis
· Evidence of persecutory voices/beliefs
· Family history of serious psychiatric problems or suicide
· Presence/influence of hopelessness
· Prior suicide attempt
· History of socioeconomic deprivation/financial worries
· History of alcohol and/or drug misuse
Management of side effects of medication
Drug side-effects
Movement disorders like tardive dyskinesia (TD), can be more
persistent and disabling in older people. TD can lead to a
number of physical and psychological complications such as
difficulty in eating and swallowing, weight loss, falls, poor
balance and depression. The risk of developing TD from
conventional antipsychotics is five to six times higher in older
people and recent studies indicate that atypical antipsychotics
may have a lower risk of TD and may therefore be safer in
this age group. A large multicentered study comparing the
mortality risk posed by typical and atypical antipsychotics
reported a 37 per cent higher risk of death in people who went
on a typical antipsychotic and that risk was dose dependent.
In a clinical setting, it is useful to follow the principle ‘start low
and go slow’ for prescribing antipsychotics to older people.
CONCLUSION
Psychotic symptoms in older people can be caused by a wide range
of factors including common physical problems, environmental
factors, cognitive decline and functional illnesses are responsible
for psychotic symptoms in older people. The diagnosis and
management of psychosis in older people is a complex process
that should take into account all these factors and should not be
limited to the use of antipsychotic medication alone.
SUGGESTED READING
1. Shiv Gautam, Gopal Bhatia, Aftab Khan, Preeti l. odha, Navendu Gaur
clinical practice guidelines on psychoses in elderly, Indian Psychiatry
society 2007 (11 – 50).
2. Salman Karim, Diagnosis and Management of Psychosis in older people
prescriber 19 jan. 2008
3. Naresh Nebhinani, Vrinda Pareek, Sandeep Grover, General of Geriatric
Mental Health jul-dec 2014 (vol.1) issue 2
4. Michael M. Reinhardt. Carl l. Cohen, Current Psychiatry Rep. (2015) 17:1
DOI 10.1007/s 11920-014-0542-0
5. Mark A. Colijn, Bradley H. Nitta, George T. Grossberg copyright@2015
President and fellows of Harvard College. Unauthorized reproduction of
this article is prohibited, Volume 23 number 5, Sep/Oct 2015.
6. American Psychiatric Association. Diagnostic and statisticalmanual
ofmental disorders. 5th ed. Arlington, VA: APA, 2013.
7. Robins LNR, Regier DA. Psychiatric disorders in America: the
epidemiologic catchment area study. New York: Free, 1991.
8. Iglewicz A,Meeks TW, Jeste DV. New wine in old bottle: late life psychosis.
Psychiatr Clin North Am 2011;34:295–318.
9. Howard R, Rabins PV, Seeman MV, Jeste DV. Late-onset schizophrenia
and very-late-onset schizophrenia-like psychosis:an international
consensus. The International Late-Onset Schizophrenia Group. Am J
Psychiatry 2000;157:172–8.
10. Vahia IV, Palmer BW, Depp C, et al. Is late-onset schizophrenia a subtype
S370
of schizophrenia? Acta Psychiatr Scand 2010;122:414–26.
11. Mason O, Stott J, Sweeting R. Dimensions of positive symptoms in late
versus early onset psychosis. Int Psychogeriatr2013;25:320–7.
12. Perala J, Suvisaari J, Saarni SI, et al. Lifetime prevalence of psychotic and
bipolar I disorders in a general population. ArchGen Psychiatry 2007;64:19–28.
13. Rush AJ. The varied clinical presentations of major depressive disorder. J
Clin Psychiatry 2007;68 suppl 8:4–10.
14. Gournellis R, Oulis P, Rizos E, Chourdaki E, Gouzaris A, Lykour as L.
Clinical correlates of age of onset in psychotic depression. Arch Gerontol
Geriatric 2011;52:94–8.
15. Ropacki SA, Jeste DV. Epidemiology of and risk factors for psychosis of
Alzheimer’s disease: a review of 55 studies published from 1990 to 2003.
Am J Psychiatry 2005;162:2022–30.
16. Jeste DV, Finkel SI. Psychosis of Alzheimer’s disease and related
dementias. Diagnostic criteria for a distinct syndrome. Am J Geriatric
Psychiatry 2000;8:29–34.
17. Sweet RA, Bennett DA, Graff-Radford NR, Mayeux R, National Institute on
Aging Late-Onset Alzheimer’s Disease Family Study Group. Assessment
and familial aggregation of psychosis in Alzheimer’s disease from the
National Institute on Aging Late Onset Alzheimer’s Disease Family Study.
Brain 2010;133:1155–62.
18. Fenelon G, Soulas T, Zenasni F, Cleret de Langavant L. The changing
face of Parkinson’s disease-associated psychosis: across-sectional study
based on the new NINDS-NIMH criteria. Mov Disord 2010;25:763–6.
19. Archibald NK, Clarke MP, Mosimann UP, Burn DJ. Visual symptoms in Parkinson’s
disease and Parkinson’s disease dementia. Mov Disord 2011;26:2387–95.
20. Friedman JH. Parkinson disease psychosis: update. Behav Neurol
2013;27:469–77.
21. Nagahama Y, Okina T, Suzuki N, Matsuda M, Fukao K, Murai T.
Classification of psychotic symptoms in dementia with Lewy bodies. Am J
Geriatric Psychiatry 2007;15:961–7.
22. Ferman TJ, Arvanitak is Z, Fujishiro H, et al. Pathology and temporal
onset of visual hallucinations, misperceptions and family misidentification
distinguishes dementia with Lewy bodies from Alzheimer’s disease.
Parkinsonism Relat Disord 2013;19:227–31.
23. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of
dementia with Lewy bodies: third report of the DLB Consortium. Neurology
2005;65:1863–72.
24. Palmer, B. W., McClure, F. S. & Jeste, D. V. (2001)Schizophrenia in late life:
findings challenge tradition concepts. Harvard Review of Psychiatry, 9, 51–58.
25. Lisa, T., Zorrilla, E. & Jeste, D. (2002) Late-life psychotic disorders:
nosology and classification. In Principles andPractices of Geriatric
Psychiatry (2nd edn) (eds J. R. M.Copeland, M. T. Abou-Saleh & D.
Blazer), pp. 493–496.Chichester: John Wiley & Sons.
26. Tune, L. E. & Salzman, C. (2003) Schizophrenia in late life. Psychiatric
Clinics of North America, 26, 103–113.
27. Wood KA, Harris J, Morreale A, et al. Drug-induced psychosis and
depression in the elderly. Psychiatr Clin North Am 1988;11:167–193.
28. Targum SD, Abbott JL. Psychoses in the elderly: a spectrum of disorders.
J Clin Psychiatry 1999;60(suppl 8):4–10.
29. Holroyd S, Laurie S. Correlates of psychotic symptoms among elderly
outpatients. Int J Geriatric Psychiatry. 1999;14:379–84.
30. Webster J, Grossberg GT. Late-life onset of psychotic symptoms. Am J
Geriatric Psychiatry. 1998;6(3):196–202.
31. Marsh CM. Psychiatric presentations of medical illness. Psychiatric Clin N
Am. 1997;20(1):181–204.
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Clinical Practice Guidelines for management of Sexual Disorders in Elderly
T.S. Sathyanarayana Rao1, Abhinav Tandon2, Shivanand Manohar1, Supriya Mathur1
Department of Psychiatry, JSS Medical College and Hospital, JSS University, Mysore. 2Neuropsychiatrist& Director,
1
Dr AKT Neuropsychiatric Centre, Allahabad. tssrao19@yahoo.com
Other Experts Participants: Mukesh P Jagiwala, Tushar
Jagawat, Mrugesh Vaishnav
INTRODUCTION
Sexuality is an important component of emotional and
physical intimacy that most men and women desire
to experience throughout their lives. Although it is a
fundamental driving force, human sexuality is frequently
misunderstood. Even among clinicians who acknowledge
the relevance of addressing sexual issues in their patients,
there is a general lack of understanding of the optimal
approach for sexual problem identification and evaluation.
In line with the worldwide trend the number of older adults
is notable and is growing in India. The latest data by the
Ministry of Statistics and programme implementation in
2016 shows that India has a total of 103.6 million elderly
and their population has risen from 5.6% to 8.6% in the
last 5 decades, thus this topic which is frequently neglected
in the elderly takes on particular importance.
Sexual life continues to be important in later life and the
elder often view sexuality as an expression of passion,
affection, admiration and loyalty .Sexual activity is a means
for elder to affirm physical functioning, to maintain a strong
sense of identity and establish self-confidence. Studies show
that sexual desire does not change with older age and it is
important for both men and women. Even in elderly women
after menopause, the sexual ability does not completely
disappear but it is affected by sexual dysfunction, either in
oneself or in the partner.
Sexual functioning is a complex combination of bio-psycho-
social process which is coordinated by neurological,
vascular and endocrine systems and any approach to
the study of human sexuality that stresses only in one
dimension is counter-productive. Recent studies suggest
sexual functioning are influenced by factors representing
three domains: biologic (the drive), psychological (the will),
social context (the wish), and interactions between them.
Sexual function and activity are closely linked with physical
health, hence understanding sexual function in the later
© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
life course is important from a medical standpoint. Poor
sexual function can be due to an underlying serious health
condition. For example, it has been found that erectile
dysfunction in men may be a marker for asymptomatic
coronary artery disease. Diabetes mellitus, which has
vascular effects on blood vessels, is one of the most
frequent systemic disorders associated with low sexual
desire and other sexual problems in aging men whereas
diabetic neuropathy can cause impaired sexual desire in
women.Understanding the sexual behaviour may uncover
protective health effects. Laumann and colleagues
discovered an association between sexual well-being and
happiness.
Numerous prescription drugs have adverse effects
on sexual functioning including antidepressants
especially SSRI’s (causing anorgasmia, erectile
dysfunction, decreased libido) and antihypertensives
(Diuretics,calcium channel blockers). Moreover adverse
drug effects are reported much more frequently in the
aging population than in the general population. The
use of prescribed medications and the rate of adverse
effects of drug therapy are consistently higher in female
than male elderly populations and they influence sexual
responses including desire by non-specific effects on
general well-being, energy levels and mood.
Psychological factors (the will) are major determinants
of intensity of sexual desire. Psychological factors are
independently related to sexual functioning.In addition
emotional and interpersonal motivation mediates the effect
of sexual drive which is characterized by willingness of
person to behave sexually with a given partner and can
compensate for diminished physiologic desire of sexual
activity (eg as result of declining testosterone levels).
Psychological condition such as depression is a risk
factor for sexual dysfunction along with the medications
associated with treating it.
Social context (the wish) also plays a crucial role in sexual
function- a role that has been neglected in medical literature.
For e.g availability of a partner, intimate communication,
relationship duration, characteristics of an individual’s
sexual partner and cultural experiences. Furthermore,
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Rao TSS et al: Management of Sexual disorders in Elderly
Table 1 : Myths associated with Elderly Sexuality11
•  Quality of sex declines with age for both sexes.
•  Erectile dysfunction is inevitable and incurable without medical
treatment.
•  If a man does not get an immediate erection or a woman is not
sufficiently lubricated he or she is not aroused (Sexual arousal may not
lead to immediate physical changes in elderly)
•  If a man is no longer aroused by the mere sight of his wife he would not
be able to perform.
•  Female sexual desire decreases dramatically after menopause.
•  Females peak in their 30s and sexual responsiveness decreases later.
•  Orgasms in young age are more intense and orgasms attained through
masturbation are more enjoyable.
•  Sex should always end with orgasm.
•  Elderly with cardiovascular morbidity should avoid sexual activity
altogether.
• Only vaginal intercourse is appropriate for elderly and oral intercourse is
reserved for the young.
Laumann et al. discovered in their analyses of the Global
Study of Sexual Attitudes and Behaviours that association
among subjective sexual wellbeing and physical health,
mental health, sexual practices, and relationship context
were consistent in a broad variety of countries from each
major world region. In addition, the authors found that
men reported higher levels of subjective sexual well-being
regardless of sociocultural context. They also established
an overall correlation between subjective sexual well-being
and happiness in men and women.
Despite the importance of sexual function sexual problems
are highly prevalent yet frequently under-recognized and
under diagnosed in clinical practice. Adequate attention
to these aspects during the history taking will educate the
patients regarding the complex nature of sexuality, and
prepare them in understanding treatment and outcome
realities. The rational selection of therapy by patients is
only possible following appropriate education, including
information about sexuality and all treatment options
for sexual dysfunction. Although not always possible on
the first visit, every effort should be made to involve the
patient’s sexual partner early in the therapeutic process.
There are many myths (Table 1) prevailing in the society and
the treating physician and collaborating specialist should
possess broad knowledge about human sexuality.
Psychosocial factors affecting sexuality in Elderly
Marriage;
For woman availability of a sexually willing, capable and
socially sanctioned sexual partner appears to be the most
important factor, but problems arise as women usually
outlive men. Marital status appears to be less important
in men regarding sexual activity. As society is moving from
double standards for men and woman these differences are
narrowing. More and more older people cohabit to avoid
social insecurity; therefore one should not assume older
unmarried people are sexually inactive. Extramarital issues
should also be kept in mind.
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Families;
Many traditional and joint families, particularly in rural areas
fail to provide privacy to the elderly, young newly married
occupying the private space. Families who do not accept
the sexual needs of divorced or widowed elderly contribute
to the negative feelings of the elderly about themselves.
Medical and nursing staffs tendency to be judgmental about
sexual needs of the elderly patients, gives the impression
that this is abnormal. Total care of elderly should encompass
addressing sexual feeling and the need for privacy.
Remarriage;
Remarriage in late life may be even more satisfying than
first marriage. Remarriage is often threatening for grown up
children who throw storm of protest. Remarriage should be
encouraged as loneliness may lead to despair.
Sexuality, Education & Awareness; Education usually
removes sexual inhibition and unnecessary anxiety, and
enhances communication. Only education can give the right
attitude regarding sexuality in elderly who are widowed,
divorced or cohabiting.
Disparity in desire
Disparity in desire among couples may increase over years;
difficulties arise when one is content with holding hands
and the other partner has strong sexual urges.
Sexual interest
Individuals who enjoyed sex in younger years continue
sexual interest when they grow older and remain sexually
active in later years. Couples tend to become less inhibited
and feel free to explore varying type of sexual stimulation
as age advances.
Regular sexual expression
Regular sexual expression is important, especially for
women. Lack of regular sexual expression and privacy
correlates with a decrease interest in coitus.
Family climacteric; Faulty attitude to “change in life” may
affect the couples response if they consider that it implies
a change of status and the level of attractiveness, and the
sexual activity is inappropriate.
Women may suffer from empty nest syndrome or boredom,
and have little status of their own. They may have difficulty
in re-entering the profession of their own, or picking up
the threads of their own lives once their children have
left home. Women may link sexual capacity to maternal
capacity, and loss of reproductive capacity may be difficult
for some to accept, depending on what fertility has meant,
and whether they have had as many, too many or too few
children compared to what they wanted. Problems faced
during pregnancy, infertility and contraception also have an
impact.
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A small number of men over 60 years also experience a
syndrome called male climacteric. This is characterized
by four or more of the following symptoms; listlessness,
weight loss, poor appetite, depressed libido, loss of erectile
potency, impaired ability to concentrate, weakness, easy
fatigability and irritability. The differentiating and deciding
factor is level of testosterone.
HORMONES
Decrease in testosterone concentrations (normal 270-1100
ng/dl) are noted from the age of 50 years, at the rate of 100
ng/dl per decade and the sensitivity of androgen receptors
decreases in men with age; however healthy aging men
never become hypogonadal. Testosterone levels in saliva of
heterosexual adolescent men correlate positively with the
number of times they initiated sexual contact (although
whether sexual contact led to the increase in androgens
needs to be confirmed). In both men and women,
orgasm (induced by masturbation) increases sympathetic
activation leading to an increase in heart rate, blood
pressure and plasma noradrenaline levels (transiently) an
increase in plasma prolactin level for 30 min in men and
60 min in women. In women, sexual arousal increases
plasma luteinizing hormone and testosterone levels. The
neurohormone oxytocin is also released during orgasm and
reinforces pleasure.
ILL HEALTH
Hypertension Causes endothelial dysfunction by shear stress
leading to reduced vasodilation and problems with
erection & Vulvar /Vaginal Congestion19
Vascular disease Erectile dysfunction is a marker of cardiovascular
dysfunction. 30% of men with Coronary Artery
Disease have sexual dysfunction. Women with
Coronary Artery disease have impairment in desire,
orgasm,arousal & number of intercourse20
Cerebrovascular 20-75% of people having stroke have sexual
Accidents dysfunction.Post stroke sexual dysfunction is due
to autonomic dysfunction, imbalance between
sympathetic over activity and parasympathetic
hypoactivity21,22
Proctectomy Sexual impairment is reported in both in men and
women. Male report more distress even after years
of surgery.23
Prostate Illness Lower urinary tract symptoms (LUTS) is most
commonly associated with Benign Prostatic
Hypertrophy. LUTS is associated with erectile and
ejaculatory dysfunction.24
Diabetes Mellitus Erectile dysfunction in males
Loss of sexual desire in both males and females25
Arthritis Pain, Negative body image, morning stiffness and
increased fatigue dampens sexual desire.26
Hip and knee immobility causes difficulty in
performing sexual acts.
Androgen Affects all phases of sexual response cycle.27
deficiency and
Hyperprolactinemia
Depression and Sexual Dysfunction
Antidepressant
Medications
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EFFECTS OF AGEING ON SEXUAL RESPONSE
CYCLE
The capacity to respond to sexual stimulation is effectively
retained, although the intensity of physical reaction is
slowly reduced in all phases of sexual response cycle. Table
2 mentions the changes in sexual response seen with aging.
Sexual Problems: Classification and Epidemiology
The ‘Sexual Response Cycle’ was described first by Masters
and Johnson in 1966 as the EPOR Model (Excitement,
Plateau, Orgasmic and Resolution phases) and later modified
by Kaplan in 1974 into the DEOR model (Desire, Excitement
, Orgasmic and Resolution phases), which became the
accepted model universally. Classically, sexual inadequacy
refers to some specific disruption of the ‘Sexual Response
Cycle’ (as described by Masters and Johnson in 1970). The
clinicians initially faced the difficulty of ascertaining the
threshold for sexual disorders. This difficulty was overcome
by adopting a patient centered approach. Accordingly, a
sexual problem is said to be present when an individual
comes with difficulty in particular area of sexual functioning
which may or may not be associated with behavioral, mood
or cognitive symptoms. As per the DEOR model “Sexual
dysfunction is referred to aproblem during any phase of the
sexual response cycle that prevents the individual or couple from
experiencing satisfaction from the sexual activity”. Gender
identity disorders and paraphilias should be differentiated
from sexual inadequacies.‘Sex’ is most commonly referred
to as what an individual is biologically, whereas ‘gender’ is
what one becomes in the social context.
DSM-5 (Diagnostic and Statistical Manual of Mental
Disorders 5th Edition) released in May 2013 defines Sexual
Dysfunctions as “a heterogeneous group of disorders
that are typically characterized by a clinically significant
`disturbance in a person’s ability to respond sexually or
to sexual pleasure” Subtypes can be classified as Lifelong
vs acquired and generalized vs situational. Other factors
which may influence the symptom presentation include i)
Partner’s and individual vulnerability factors ii) Relationship
issues iii) Psychiatric comorbidity iv) Cultural and v) General
medical factors.
Common Sexual Problems and Dysfunctions
Classification in psychiatry has been a topic of debate and
complex area of research. Some are of the opinion that
classificatory system creates artificial boundaries between
different category of problems; one the best examples for
the same is merging of female sexual desire disorders and
arousal disorders in DSM-5. Due to its eclectic approach
the International classification of mental disorders (ICD-
10) has been clinically acceptable in India. The DSM
classificatory system by the American Psychiatric Society
has been acceptable in academic institutions due to its
pointwise approach. DSM 5 highlights the fact that clinical
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Table 2: Changes in sexual response with aging Table 3 Comparison of diagnostic categories of ICD‑10
SEXUAL MALE FEMALE & DSM‑5 of sexual disorders9
RESPONSE Disorders according ICD‑10 DSM‑5
CYCLE to sexual cycle
Excitement Erection takes longer Excitement phase takes longer Sexual desire Lack or loss of sexual Male hypoactive sexual
time and somewhat lost time disorders desire desire disorder
(Physiological impotence) Sexual aversion Female sexual interest/
Plateau Plateau phase is extended Excessive sexual drive arousal disorder
Orgasm Orgasmic phase is shortened. Woman remain capable of Sexual arousal Failure of genital MaleErectile disorder
Ejaculation may not happen having multiple orgasms Disorders response
on every occasion.The throughout their lives without Orgasm disorders Orgasmic dysfunction Male
volume, expulsive force and any refractory period Lack of sexual Premature (early)
biphasic characteristics of enjoyment ejaculation
ejaculation decline Premature ejaculation Delayed ejaculation
Resolution Refractory period is increased Resolution is more rapid Female
Orgasmic disorder
WOMEN Sexual pain disorders Nonorganic dyspareunia Female
Nonorganic Vaginismus Genito‑pelvic pain/
General Changes · Increased response time penetration disorder
· Decreased tone, strength and elasticity of Other sexual Paraphilias Substance/Medication
tissue disorders/ problems Gender identity induced sexual dysfunction
Clitoris · Slower and reduced tumescence disorders Other Specified Sexual
· Clitoral Head atrophy Other sexual Dysfunction
Labia Majora · Reduced flattening and separation dysfunction, not caused Unspecified Sexual
Labia Minora · Reduced thickening and expansion by Dysfunction
· Changes in color organic disorder or Paraphilic disorders
disease Gender Dysphoria
External Urinary Meatus · Gaping during orgasms, which may lead to Unspecified sexual Gender Dysphoria in
post coital dysuria/burning for as long as dysfunction, not children
2 days, sometimes associated with urinary caused by organic Gender Dysphoria in
urgency and incontinence disorder or disease adolescent and adults
Vagina · Shorter, narrower with decreased ability to Other specified Gender
expand. Dysphoria
· In women > 40 years Vaginal lubrication Unspecified Gender
time is increased to 2-3 minutes as compared dysphoria
to 30 seconds in younger age group.

MEN
subtypes include, lifelong which denotes that the problem
has been present from the very beginning; acquired denotes
Speed and · Reduced vasocongestive responses
Intensity · Decreased frequency of sexual activity, morning
that the problem started after a period of normal sexual
erections and nocturnal emissions functioning.Generalized (vs Situational) denotes that the
Erections · Takes longer time and requires more direct stimulation. sexual problem is present with all types of stimulation, all
· Penile tumescence slower, reduced in size and turgidity. situations and partners. Other factors which need to be
· Erections may be lost and difficult to regain considered include: 1)Partner factors (sexual problems in the
· Erections may be maintained for longer duration but with
decreased angle of penis
partner),2) Relationship factors, 3) Individual vulnerability
· Deepening of colour of glans factors (poor body image), 4) Cultural or religious factors,
· Elevation of testes 5) Medical factors. As per DSM 5, if the sexual problem is
· Myotonia due to a non -sexual mental disorder (anxiety, depression),
· Sex flush
substance use, other medical condition or severe
· Preejaculatory secretion
Ejaculation · Decreased incidence relationship distress then a sexual dysfunction diagnosis is
· Decrease in intensity not made.Table 3 gives a comparison of sexual dysfunctions
· Reduced or absent ejaculatory inevitability mentioned in DSM 5 and ICD 10 Classification of Mental
· Reduced or absent volume force duration and expulsive and Behavioral Disorders (International Classification of
contractions
· Reduced or absent awareness of orgasm
diseases10th Revision) Table 4 gives a brief description of
· Lesser rectal sphincter contractions sexual dysfunctions mentioned in DSM 5.
· Premature ejaculation
Sexual Dysfunctions: Epidemiology
Detumescence · Very rapid but with longer refractory period The frequency of reporting and seeking help for sexual
problems varies due to a number of factors like availability
judgement needs to be applied to ascertain whether the of sexual health care facility, awareness about the problem
sexual dysfunction is due to inadequate stimulation.DSM-5 and the social and cultural factors. Geriatric sexuality

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Table 4 : Brief description of sexual dysfunctions literature constitutes only 0.5 % of the total publications,
mentioned in DSM 5 and still very few from the developing world. Logistical
DSM-V (Diagnostic and Statistical Manual of Mental Disorders 5th issues, sexuality specific venues competing for publication
Edition) and geriatric journals avoiding sexuality related topics in
Delayed Ejaculation: Marked delay of ejaculation; infrequent or absence elderly, contributes to low research volume on geriatric
of ejaculation:* sexuality.Studies involving both the genders in the age
Specify- Lifelong vs Acquired; Generalized vs Situational; Mild, moderate
group more than 50 years, reports prevalence of sexual
or severe.
Erectile Disorder dysfunction to be around 50-80%.
Marked difficulty in obtaining an erection during sexual activity or
maintaining an erection during sexual activity or marked decrease in Studies involving females in the age group of 50-70 years,
erectile rigidity:* reports prevelance of sexual dysfunction to be around 50-
Specify- Lifelong vs Acquired; Generalized vs Situational; Mild, moderate
75%.
or severe.
Female Orgasmic Disorder
Marked delay, infrequent, reduced intensity or absence of orgasm:* Sexual Dysfunctions: Etiology
Specify- Lifelong vs Acquired; Generalized vs Situational; Mild, moderate Human sexual response is a complex biological phenomenon
or severe. and is strongly influenced by interpersonal and socio-cultural
Female Sexual Interest/ Arousal Disorder#
Significantly reduced or absence of sexual interest or arousal which may
include any 3 of the following: (1) Absent/Reduced interest (2) Absent/ Table-5: Etiology of sexual disorders
reduced erotic thoughts (3) Absent/reduced initiation of sexual activity or Partner Factors • Partner’s sexual problems
no response to partner’s attempt to initiate the same (4) Absent/Reduced • Partner’s poor health
sexual excitement in 75-100% encounters (5) Absent/reduced response to Relationship Factors • Poor communication, lack of Intimacy
erotic cues (6) Absent /reduced genital or non-genital sensations during • Discrepancy in sexual desire
sexual activity in 75-100% encounters. Psychiatric Comorbidity • Depression, psychotic disorders, dementia
Symptoms mentioned above are present for a minimum period of 6 months (Nonsexual mental Disorder) • Anxiety, obsessive compulsive disorders
and cause clinically significant distress. Individual factors • Poor body image
Specify- Lifelong vs Acquired; Generalized vs Situational; Mild, moderate Sociocultural and religious • Certain cultures consider sex as
or severe. factors appropriate only for the young
Male Hypoactive Sexual Desire Disorder • Various myths associated with elderly
Persistently deficient or absent sexual thoughts or fantasies and desire for sexuality
sexual activity. The judgement is made by taking into consideration the age Medical Factors • Cardiovascular comorbidity, neurological
and socio-cultural factors. The symptoms are present for a minimum period disorders, infections, malignancies,
of 6 months and cause significant distress. endocrinal disorders
Specify- Lifelong vs Acquired; Generalized vs Situational; Mild, moderate • Pelvic nerve damage, Diabetes, traumatic
or severe. surgical injury
Premature (Early) Ejaculation • Drugs
Persistent or recurrent ejaculation occurring during sexual activity with Substance Abuse • Alcohol, smoking
partner, within 1 minute of vaginal penetration and before the individual
wishes:*
This diagnosis may be applied in cases of non-vaginal sexualactivities. Table 6: Common Drugs associated with male sexual
Specify- Lifelong vs Acquired; Generalized vs Situational; Mild, moderate dysfunction and alternative safer drugs available
or severe. Drugs Associated Notes for alternative safer
Genito-Pelvic Pain/ Penetration Disorder Dysfunctions drugs
Persistence of any of the following symptoms: (1)Difficulty in vaginal
First generation Erectile Quetiapine and Aripriprazole
penetration (2)Significant pain during vaginal intercourse /penetration
antipsychotics,49many Dysfunction, have minimal side effects
(3) Fear/anxiety or pain in anticipation during vaginal penetration 4)
second generation Multiple phases and don’t lead to prolactin
Significant contraction of pelvic floor muscles during vaginal penetration
antipsychotics of sexual elevation
attempt.
function
The symptoms are present for a minimum period of 6 months and cause
Tricyclic Antidepressants, Erectile Among Antidepressants
significant distress.
SSRIs (Selective Serotonin Dysfunction Bupropion, Mirtazapine,
Genito-pelvic pain disorder can be further classified into (1) Lifelong vs
Reuptake Inhibitors)50 Decreased Duloxetine and Nefazodone
Acquired & (2) Mild, Moderate or Severe.
Benzodiazepines Libido have minimal side effects.51
Other Sexual Dysfunctions mentioned in DSM-5
Alcohol, Ketoconazole, Ejaculatory
Substance/Medication induced Sexual Dysfunction (Specify whether
Phenobarbital, Phenytoin Dysfunction
onset is during intoxication, during withdrawal or after medication use)
Antihypertensives Erectile ACE (Angiotensin Converting
Other Specified Sexual Dysfunction (diuretics : Dysfunction Enzyme) inhibitors like
Unspecified Sexual Dysfunction hydrochlorothiazide , Decreased Ramipril, ARBs (Angiotensin
For making any of the above diagnosis as per DSM-5, a nonsexual sympatholytics : Clonidine, Libido Receptor II blockers ) like
mental disorder, substance abuse/ general medical cause leading to sexual nonselective beta blockers, Ejaculatory Losartan and Calcium channel
dysfunction and severe relationship distress should be ruled out. alpha blockers) Dysfunction blockers (Amlodipine,
*On almost all or greater than 75% occasions of sexual activity with a partner Antiandrogenic Diltiazem, Verapamil) are
(in identified situations or, if generalized, in all situations), and without the Drugs(Digoxin, Histamine neutral towards sexual
individual desiring delay. The symptoms are present for a minimum period of 6
months and cause significant distress.
H2 receptor blockers functioning.20

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factors. Generally speaking, sexual dysfunctions are multi- should be considered and enquired. Sexual orientation
factorial in etiology. As mentioned, DSM-5 highlights the of the patient, any high risk sexual behaviour and sexual
point that a sexual dysfunction diagnosis is not made if the abuse history should be kept in mind. Regardless of sexual
problem is better explained by a nonsexual mental disorder, orientation, each phase of the sexual response cycle applies
stressor, substance use or a general medical condition. equally to both heterosexual and homosexual partners and
Table-5highlights the etiology of sexual disorders, whereas methods and principles of treatment are similar. Table 8
table 6 and 7 mention the drugs most commonly associated highlights the points to be considered for taking a sexual
with sexual dysfunction in the elderly male and female. history; whereas table 9describes the assessment of current
sexual functioning in males and females.
MANAGEMENT OF SEXUAL INADEQUACIES
Careful history taking should be followed by a physical
Diagnostic workup examination in all the cases after obtaining consent
As in all psychiatric interviews one needs to develop rapport and maintaining privacy. Rule out organic disease and
in an accepting atmosphere with a non-judgmental attitude. make a note of any contributing general medical illness.
Sexual history needs to be more structured, though areas Laboratory studies include urine analysis, complete blood
of concern for the patient should be explored positively. count, kidney and liver function tests, lipid profile, fasting
Both recent and early sexual histories need to be noted. The
current sexual complaints, life stresses, sexual practices,
Table 9: Assessment of current sexual functioning in
contraceptive use, partners, relationship problems,
males and females
sexual fantasies, masturbatory history, extramarital affairs
Current Sexual Functioning Current Sexual Functioning
and commitment to partner should be enquired into. If
(Males) (Females)
married courtship period, honeymoon and reproductive
Libido/Interest: Libido/Interest:
history should be looked into. Mutual physical attraction, Do you remain interested in sexual Do you remain interested in sexual
temporary separation and the effect of children on couple’s activity? activity?
sexual life should be noted. Changes in sexual functioning Whether you dream/fantasize Whether you dream/fantasize about
and frequency and quality of sexual interactions with about sex? How easily are you sex?
age should be detailed. The partner’s contribution to aroused? Do you enjoy sexual activity?
Do you enjoy sexual activity? How easily are you aroused?
the present distress, life style factors, psychiatric history How strong is your sex drive?
including history of substance abuse should be ascertained. Arousal and Performance: Arousal and Performance:
The patient’s self-image as a sexual being through childhood When was the last time you got a Subjective excitement during
and adolescence and people who contributed to patient’s satisfactory erection which can be intercourse?
maintained? Moistening of Vagina?
sexual education and identity needs to be detailed. Any
Was the Onset of the problem- Orgasm/Satisfaction:
history of group sex, homosexual encounters and abortions Gradual/Sudden? Do you achieve orgasm during sexual
Sexual stimulation and time activity?
required for erection? Whether it Whether orgasm is delayed/ absent?
Table 8: Taking a Sexual History53 can be maintained? frequency?
Individual’s Name, Age, Sex, Occupation, Relationship status Whether you need to concentrate Do you get adequate stimulation during
Identifying Data ( single, married, previous marriages, separated, in maintaining an erection? sexual activity? Stimulation during
divorced, cohabiting), sexual orientation Loss of erection before masturbation/ mutual masturbation?
Current sexual Satisfactory or not penetration? Pain during erection? Trust on partner or any associated
functioning Sexual dysfunctions (Onset-lifelong or acquired / Situation/partner specific erectile fears?
Generalized/Situational-in a particular situation problems?
or only with the current partner or only during Difficulty with certain sexual
masturbation) positions?
Frequency (decreased in elderly),Desire/Libido Ejaculation/orgasm Pain/Vaginismus
(How frequently Sexual fantasies are experienced) Whether you ejaculate during sex / Where and when does the pain occur?
Sexual Interaction Description (Initiation, foreplay, masturbation? During partial/deep penetration,
coital positions, verbalization, afterplay, feelings How long do you take to thrusting, ejaculation, withdrawal,
post sexual activity ejaculate? during micturition? Describe the pain.
Any compulsivity related to sex Do you ejaculate before you or Tensing of body during partner’s
Past Sexual History Childhood and Adolescent sexuality/ sexual your partner wants to? Frequency? attempt?Your thoughts and feelings at
activities Reaction of partner? that time?
Adult Sexual activities including premarital sex and Is your ejaculation delayed? Pain during other forms of penetration
Marriage(marital and extra marital sex) Frequency? (finger)? Pain while bicycling or
Psychosocial History Sexual myths, Sociocultural factors Do you have pain during wearing tight clothes?
Psychiatric & Depression, Psychotic illness, Cardiovascular ejaculation? Do you feel the tensing of pelvic floor
Medical History comorbidity, Diabetes, Neurological problems, Do you reach Orgasm? muscles during sexual activity/other
Drugs Frequency? acts?
Other important Sexual or Physical abuse, Gender Identity conflict, Is your partner satisfied? Do you have a drying up feel of the
issues Paraphilias vagina?

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Table10: Differentiating features between organic and

psychogenic sexual dysfunction9
Parameters Psychogenic Organic
Onset of disorder Situational Insidious
Precipitating event Psychogenic condition Debilitating disease, vascular
insufficiency or CNS
abnormality, penile trauma or
interfering drugs
Erectile response to Usually present Usually absent
other sexual stimuli
Nocturnal or Initially present and Absent or reduced in
morning erections full, lost in longstanding frequency and intensity
Dysfunction
Course of disorder Episodic or transient Persistent and progressive
loss of erection erectile
Dysfunction
Associated Premature ejaculation Retrograde or absent
ejaculatory disorder and intermittent loss of ejaculation
Ejaculation

blood sugar,ECG, thyroid function. Other endocrinal

tests and Lab tests related to general medical illness if
any or only when needed. Nocturnal penile tumescence,
Intracavernosalinjection using avasodilating agent like
papaverine, duplex color ultrasonography, dynamic
infusioncavernosometry and cavernosography, pelvic penile
angiography are the other tests in some selected cases
and depends on what procedure is being planned . It is
necessary to understand relationship difficulties among the
couple, whether partner is sympathetic or not sympathetic
towards the problem, their expectation and motivation for
treatment. Differentiating features between organic and
psychogenic sexual dysfunction need to be established well
before the active management as mentioned in table 10.
PSYCHOTHERAPEUTIC INTERVENTION
Sex therapy as it is referred to today is essentially a
modified form of the original therapy (as founded by
Masters and Johnson in 1970) and follows a brief, problem
focused, and behavioral approach. Based on classic
psychodynamic theories, resolution of early developmental
conflicts, acceptance of sexual impulses to the ego and
resolution of the problem was the main focus. The ‘new’
sex therapy focuses on relief of immediate symptoms and
acts as a bridge between the psychoanalytic and behavioral
approaches. Psychodynamic approaches are only used if
the initial behavioral techniques do not produce symptom
relief.
As elaborated by Masters and Johnson in 1970, sex therapy
(dual sex therapy) ideally includes involvement of both
the partners. Anatomy and physiology of sexual function
are explained in brief and doubts are cleared. Therapy
emphasizes that there is no use blaming one’s partner or
oneself, and sex is a mutual act between two individuals.
Interpersonal communication at a highly intimate level and
enhanced social communication benefits the relationship.
Education,heightening sensory awareness and sensate focus
exercises are taught to the couple. Behavioral exercises
include sensate focus (non-demand pleasuring), to allow the
individual to re-experience pleasure without any pressure
of performance or self-monitoring. The assessment and
treatment need to be tailored depending upon one’s setting,
profession, specialty and most important of all, the type of
the problem encountered in the client, wherein different
approaches may be helpful.
PHARMACOTHERAPY FOR SEXUAL
DYSFUNCTION
Nitric oxide enhancers:
These drugs improve inflow of blood into the penis and
improve erection. First drug developed in this class was
sildenafil citrate. It acts on the nitric oxide mechanism
by blocking PDE - 5 (Phosphodiesterase-5) enzyme. It
is the first approved non-surgical treatment for erectile
dysfunction and was approved by US Food and Drug
Administration (US-FDA) in 1998 for prescription sale. It is
rapidly absorbed after oral administration and has to be
taken one hour before sexual activity which is the time
required for peak plasma concentrations to be reached
and the effect may last for upto 4 hours. The starting

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PSYCHOTHERAPEUTIC INTERVENTION KEY POINTS

SEX THERAPY(Dual Therapy)53
BEHAVIORAL TECHNIQUES
·• Brief , problem focused and behavioral approach
·• Focus on relief of immediate symptoms and acts as a bridge between the psychoanalytic and behavioral
approach.
·• The assessment and treatment need to be tailored depending upon one’s setting, profession, specialty
and most important of all, the type of the problem encountered in the client
·• Involves both partners
·• Anatomy and physiology of sexual function are explained and doubts are cleared
·• Emphasizes on not to blame one’s partner or onself and that sex is a mutual act between two individuals
and interpersonal communication at a highly intimate level and enchanced social communication
benefits the relationship
·• Education, heightening sensory awareness and sensate focus exercises are taught to the couple.
·• Behavioral exercises include sensate focus (non-demand pleasuring), to allow the individual to re-
experience pleasure without any pressure of performance or self-monitoring.
·• Using a hierarchy of anxiety provoking sexual interactions the client systematically desensitized
·• Different approaches include Masters and Johnson’s approach, Kaplan’s approach and the PLISSIT
MODEL with some variations in the treatment process.
PLLISIT MODEL - Proposed by Annon
·• Graded Intervention wherein individual letters stand for 55,56 :-

-• P: Permission Giving

OTHER THERAPIES
Couple Therapy & Family Therapy
(Marital & Family Counselling)
Emotions Focused Couples Therapy
Behavioral Marital Therapy
Cognitive Behavioral Couple Therapy
-• LI: Limited Information
-• SS: Specific Suggestion
-• IT: Intensive Sex Therapy
·• Permission giving: The first phase client is assured that their thoughts, feelings, fantasies and behaviors
are normal till they are not affecting the partner in a negative manner.
·• Limited Information : Phase the client is given information related to his/ her sexual problem.
·• Specific Suggestion: Behavioral exercises like start- stop technique, ‘sensate focus’ are taught and
home-work assignments are given. These help in improved communication between the couple and in
learning new arousal behaviors.
·• Intensive therapy: Considered if the first three fail. Insight oriented and psychosexual approaches are
taken to make the client aware of their feelings.
·• Sex therapy involves primarily Sensitization, desensitization techniques. The general principles are
applicable to majority of the inadequacies encountered in clinical practice. The major guide-lines to be
followed are (i) Educating the couple (ii) Setting the framework for the therapy (iii) Proscribe sex (iv)
Sensate focus exercises (v) Systematic Sensitization & Desensitization: The couple is advised to talk
on issues bothering them in a nonjudgmental way, encourage partners to see, hear and understand each
other’s perception and teach verbal and nonverbal communication skills, in general and during sexual
activity, in particular.57,58,59
·• The therapist works with families and couples in intimate relationships, regardless of whether the client
considers it to be an individual or family issue.
·• Eclectic approach: Therapist uses a theoretical concept which leads to improvement of a couple’s
relationship. Ideally, in marital therapy both partners are counselled together. It is important to first
ascertain whether love and concern exists for each other.
·• Communication pattern between the couple and the power structure of their relationship needs to be
ascertained.
·• The therapist could by exaggeration highlight the method of relating to each other in a couple and
their communicative pattern. The therapist by modelling demonstrates methods like genuine listening,
encouraging and empathizing by which love and tenderness can be expressed.52,53
·• Short term intervention to reduce distress in adult love relationships and create more secure attachment
bonds.54
·• Skill oriented approach emphasizing that couples need basic skills and understanding of relationship
interactions to improve their marriages.
·• The focus is the current marital relationship and improving positive communication.55
·• Based on the concept that relationship distress includes cognitive, behavioral and affective components
that influence each other.56

dose should be used on atleast four occasions to precisely
access the efficacy and tolerability. If a satisfactory sexual
performance is not achieved, the dose should be increased
to the next higher level. Studies have clearly demonstrated
that there is a dose-response curve with sildenafil and
the best results are obtained upto a maximum dose of
100mg. However sildenafil has been used as a salvage
therapy for severe erectile dysfunction at a maximum
dose of 200 mg, but the incidence of side effects and
discontinuation rates increase considerably. Very recent
studies have reported that sildenafil does not worsen the
cardiac profile of patients with Ischaemic heart disease,

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undergoing stress exercises. Sildenafil increases the
time to developing symptoms of angina in symptomatic
patients with Ischaemic heart diseaseundergoing a
treadmill test. Sildenafil does not cause coronary steal or
reflex tachycardia. For patients who experience an acute
myocardial ischemia and who have taken sildenafil in the
last 24 hours, administration of nitrates should be avoided.
The American College of Cardiology and the American Heart
Association have published recommendations for the use
of sildenafil in patients with cardiac risk. Sildenafil should
be used with caution in individuals maintained on multiple
antihypertensive drugs. Adverse effects with sildenafil are
dose dependent. Common adverse effects are headache
(most common), flushing, rhinitis and visual disturbance
changes in the perception of colour, hue or brightness.
The adverse effects are usually mild and transient, lasting a
few minutes to a few hours after drug administration. It is
contraindicated in patients on concurrent organic nitrates.
This is because it potentiates the hypotensive action
of such drugs through its effects on nitric oxide/c-GMP
mechanisms. It should be used with caution in persons
with anatomical deformities of the penis (e.g. Angulation,

Table 11: COMPARISON OF PDE-5 INHIBITORS9

Dosage
Time to maximum plasma
concentration (T max) in
minutes
Half‑life in hours
Plasma protein binding
Bioavailability
Onset of action in minutes
Duration of action
Absorption
Dose adjustments required
Contraindication
Side effects
Recommended time between
medication intake and
intercourse
Sildenafil
30-120 (median 60)
2.6 to 3.7
96%
41%
15‑60
4 4
Fatty meals cause a mean
delay in Cmax of
60 minutes
Patients >65 years old
• Hepatic impairment
• Renal impairment
• Concomitant use of potent
cytochrome P450 3A4
inhibitors, such as
Ketoconazole, Itraconazole,
Erythromycin,
Clarithromycin, HIV
Protease
Inhibitors (Ritonavir and
Saquinavir)
• Concomitant use of
Rifampicin, Phenobarbital,
Phenytoin and
Carbamazepine, may
induce CYP3A4
and enhance the breakdown
Concomitant use of
cimetidine
Patients receiving organic
nitrates either regularly or
intermittently
Hypersensitivity to any
component of the tablet
Headache
Flushing
Dyspepsia
Nasal congestion
Alteration in colour vision
1 hour
Vardenafil Tadalafil
30-120 (median 60) 30–360 (median 120)
3.9 17.5
94% 94%
15% Not known
25 16‑45
36
Fatty meals cause a Not affected by food
reduction in Cmax
Patients >65 years old • Patients >65 years old
• Hepatic impairment • Hepatic impairment
• Renal impairment • Renal impairment
• Concomitant use of • Concomitant use of
potent cytochrome potent cytochrome
P450 3A4 inhibitors, P450 3A4 inhibitors,
such as Ketoconazole, such as Ketoconazole,
Itraconazole, Erythromycin, Itraconazole,
Clarithromycin, HIV Erythromycin,
Protease Inhibitors Clarithromycin, HIV
(Ritonavir protease
and Saquinavir) inhibitors (Ritonavir and
• Concomitant use of Saquinavir)
Rifampicin, Phenobarbital, • Concomitant use of
Phenytoin and Rifampicin,
Carbamazepine, may Phenobarbital, Phenytoin
induce and
CYP3A4 and enhance the Carbamazepine, may
breakdown induce
CYP3A4 and enhance the
breakdown
Patients receiving organic Any patient using organic
nitrates either regularly or nitrates either regularly or
intermittently intermittently
Hypersensitivity to any Hyper‑sensitivity to any
component of the tablet component of the tablet
Headache Headache
Flushing Dyspepsia
Rhinitis Back pain
Dyspepsia Myalgia
Sinusitis Nasal congestion
1 hour 1 to 12 hours
Udenafil
 60 to 90
11–13
---
38% (studied in rats)
 Onset of action is
comparable with Sildenafil
and Vardenafil
Overall bioavailability not
affected by food.
Fatty meals cause a
reduction in Cmax
Concomitant use of
potent cytochrome
P450 3A4 inhibitors,
such as Ketoconazole,
Itraconazole,
Erythromycin,
Clarithromycin, HIV
protease
inhibitors (Ritonavir and
Saquinavir)
• Concomitant use of
Rifampicin,
Phenobarbital, Phenytoin
and
Carbamazepine, may
induce
CYP3A4 and enhance the
breakdown
Any patient using organic
nitrates either regularly or
intermittently
Hyper‑sensitivity to any
component of the tablet
Stomach discomfort,
flushing, Headache, and
Nasal congestion, Blurred
vision
1 to 12 hours

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Rao TSS et al: Management of Sexual disorders in Elderly
Cavernosal fibrosis, Peyronie’s disease), and in patients
at risk for Priapism (e.gpatients with Sickle Cell anemia,
Multiple Myeloma, Leukemia, Bleeding Disorders, Retinitis
Pigmentosa). Rare side effect reported is Nonarteritic
Ischemic Optic Neuropathy (NAION).Recent studies have
reported that metformin and pioglitazone used in diabetes
enhance the effect of Sildenafil in treating ED. Various
PDE-5 inhibitors have been compared in table 11. A long
acting PDE5 inhibitor should be considered for elderly men
who frequently have sexual intercourse in the morning
after waking up and patients who anticipate frequent
sexual intercourse.  Udenafil has clinical properties of both
relatively rapid onset and long duration of action though it
is not available in India.
Oral Phentolamine and Apomorphine are helpful as
potency enhancers in minimal erectile dysfunction.
Apomorphine effects are mediated through the autonomic
nervous system causing arterial vasodilation and has
dopamine receptor stimulating effect. Phentolamine
decreases sympathetic stimulation and relaxes corporeal
smooth muscle. Smooth Muscle relaxants like Papaverine,
Phentolamine, Phenoxybenzamine are used in ICIVAD
(Intracavernosal injection of vasoactive drugs) techniques
for ED; Prostaglandin E (Alprostadil) through injection or
through intraurethral insertion is an effective agent for
ED; to improve erectile function in animal studies and is
likely to be studied on humans 52 in near future. A topical
cream containing 3 vasoactive agents: Aminophylline,
Isosorbidedinitrate and Co-dergocrinemesylate with or
without Alprostadil is helpful in ED. An Alprostadil cream
and vaginally applied Phentolamine are helpful for female
sexual arousal disorder. Yohimbine is a central Alpha 2
adrenoreceptor blocker and increases sympathetic drive.
Its effectiveness is doubtful in ED. Horny Goat weed
(Epimedium) has been used as a traditional remedy for ED
in China. Trazodone, an antidepressant acts by inhibiting
serotonin uptake and also by influencing alpha adrenergic
and dopaminergic function. Results are inconsistent in
erectile disorders.
Pharmacotherapy of premature ejaculation includes
judicious use of tricyclic antidepressants, SSRIs and certain
topical therapies.
Hormonal therapies:
Testosterone is definitively effective only in case of
hypogonadism. It can increase the desire but has no
effect on erectile functioning. Female low sex drive
and anorgasmia can be tried under careful monitoring.
Hormone Replacement Therapy (HRT) with estrogen in
case of menopausal women as vaginal function, particularly
lubrication is determined by them. Hyperprolactinaemia
is treated by administration of dopaminergic drugs like
bromocriptine.
S406
Other drugs:
Naltrexone, an opiate antagonist, can antagonize the
inhibition of sexual functions. Aswagandha, Shathavari,
Korean red ginseng are helpful in enhancing sexual
functioning in both males and females. Aswagandha (Indian
ginseng) enhances sexual desire in men. Shathavari(Asparagus
racemosus), a creeper which grows in low jungle areas
throughout India is considered to be the women’s equivalent
to Ashwagandha and enhances female sexual functioning.
Some of the traditional herbal medicines used in medieval
Persia, have been shown to be helpful in ED by relatively recent
research. These include ginger (Zingiberofficinale), almond
(Amygdaluscommunis), spice commonly known as ‘grains of
paradise; Melegueta pepper’ (Aframomummelegueta), and
certain brassica species and seed of garden cress (Lepidium
sp). Saffron (30 mg/day) has been shown to improve sexual
function (arousal, lubrication and pain domain) in females
with SSRI induced sexual dysfunction. Snacking on pistachio
nuts, 100 gm/day for 3 weeks, has been shown to improve
erectile dysfunction.
Flibanserin (Trade name-Addyi; now available in India by the
name Fliban by Hindustan Unilever) is a medication approved
by US-FDA for the treatment of pre-menopausal women
with hypoactive sexual desire disorder (HSDD).
In some selected cases when psychotherapy, behaviour
techniques and drugs fail or seen to be not very effective,
vacuum devises, injections and implants, vibrators are
found to be relatively effective. Ultimately, the success of
sex therapy depends on a host of factors. Therapy duration
ranges from 6 weeks to more than a year in occasional
cases. Sexual dysfunctions respond to treatment better
compared to gender identify disorders and paraphilias,
which are very resistant to therapy. More than half of the
cases of erectile dysfunction and almost all the cases of
premature ejaculation respond to combination of therapies.
Gender Identity disorder / Gender Dysphoria
Although much has been written on diagnosis of gender
dysphoria, emphasis has always been on younger
individuals. While several researchers have alluded to
the problems of the aging gender dysphoric patient the
relationship between diagnosis and treatment has been
neglected. As more older gender dysphoric patients request
sex-reassignment surgery, there will be increasing demands
for differential diagnoses and treatment strategies. Correct
diagnosis is especially crucial since life stresses may lead
some transvestites to clinically present as transsexuals
desiring sex-reassignment surgery.
Sexual Variations, Paraphilia and Paraphilic Disorders
Sexual variations are very common in almost all age groups
and elderly are no exception. The term ‘deviation’ refers
to the existence of a norm and the deviation takes place.
In sexuality no such norm exists, as standard varies from
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Rao TSS et al: Management of Sexual disorders in Elderly

time to time, place to place and epoch to epoch and
culture to culture. Homosexuality has gradually come to
be considered as a variation of sexual activity rather than
deviation. However, one may encounter issues related to
them in the Indian context in the elderly and there is need
to attend to them with utmost sensitivity.
The term paraphilia denotes a persistent sexual interest
other than sexual interest in genital stimulation with
phenotypically normal, mature and consenting human
partners. These may include the person’s erotic activities
or targets. Previously considered perversions implying
sexually arousing fantasies, activities and gratification
other than by willing genital intercourse between partners
and a departure from the cultural norm. Normal sexual
relationship implies activities which are acceptable and
pleasurable to both the partners without the degradation,
exploitation or distress to either of them. Contrary to
the long held belief many paraphilic behaviours are
predominantly male, does not involve offences and
practices remain intensely private. DSM 5 recognizes
and differentiates innocuous paraphilic behaviours from
paraphilic disorders. A paraphilic disorder is a paraphilia
causing distress to the individual with or without risk
of harm to self or others. Example persistent interest in
whipping or strangulating another person.A paraphilia is
a necessary but not the only condition for diagnosing a
paraphilic disorder. Among elderly they may represent
some other primary cause and ruling out dementia, mood
disorders and personality disorders is a must. Sexually
inappropriate conduct often accompanies the disinhibition
associated with dementia and neuropsychologic deficits. A
detailed evaluation is mandatory. The treatment involves
medications, behaviour modification therapies, family
and psychotherapy and where necessary sex therapy like
reinforcement of socially acceptable sexual function and
management of erectile and ejaculatory impairment.
4. It is important that older men and women do not fall
into the psychosocial trap of expecting (or worse,
trying to force) the kind and degree of sexual response
characteristic of their youth, it is equally as important
that they not fall prey to the negative folklore according
to which decreased physical intimacy is an inevitable
consequence of the passage of time.
5. Early adoption of healthy lifestyles may be the best
approach to reducing the burden of erectile and other
sexual dysfunctions on the health and well being of
elderly.
B.  Sexual Rights
1. Sexual rights embrace human rights that are already
recognized in international human rights documents
and other consensus statements and they include the
rights of all persons, free of coercion, discrimination and
violence, to the highest attainable standard of sexual
health, including access to sexual and reproductive
health care services.
Guiding Principles for Affirmative Action propounded
C. 
by WHO implies Affirmative approach to sexuality,
Autonomy and self-determination and responsiveness
to changing needs, Comprehensive understanding of
sexuality, Confidentiality and privacy, Advocacy and
Equity, Non-judgementaland Accessible services and
programmes to the elderly.
The following flowchart gives the treatment of sexual
disorders in elderly.

CONCLUSION

Conclusions:
A.  Quality of Life
1. Aging typically entails some degree of change in men’s
and women’s capacities for sexual performance from
strictly physiological standpoint, yet research data
suggests that an equalnumber of people in late life find
sex satisfying, if not more so, than in their youth.
2. It is important to recognize that older people are at risk
of severalhealth-related, psychosocial, environmental
circumstances that can hinder sexual expression and
functioning. Although some of these barriers cannot be
prevented entirely, education, advocacy andeffective
coping strategies can soften their impact considerably.
3. An understanding of the sexual changes that accompany REFERENCES
normalaging may help physicians give patients realistic 1. Hatzichristou D, Rosen RC, Broderick G, Clayton A, Cuzin B, Derogatis L,
and encouragingadvice on sexuality. Litwin M, Meuleman E, O’Leary M, Quirk F, Sadovsky R, Seftel A. Clinical

Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018 S407

[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]
Rao TSS et al: Management of Sexual disorders in Elderly
evaluation and management strategy for sexual dysfunction in men and
women. Journal of Sexual Medicine, 2004;1:49-57.
2. Kalra G, Subramanyam A, Pinto C. Sexuality: Desire, activity and intimacy
in the elderly. Indian Journal of Psychiatry. 2011;53(4):300-306.
3. Umidi, S., et al. (2007). “Affectivity and sexuality in the elderly: Often
neglected aspects.” Archives of Gerontology & Geriatrics 44: 413-417.
4. Choi KB, Jang SH, Lee MY, Kim KH. Sexual life and self-esteem in married
elderly. Arch GerontolGeriatr. 2011 Jul-Aug;53(1):e17-20
5. Wolfe, L. D. (1995), Sexuality across the life course. Edited by A.S. Rossi.
xvii + 418 pp. Chicago: The University of Chicago Press. 1994. $34.95
(cloth). Am. J. Hum. Biol., 7: 278–279.
6. John D. DeLamater& Morgan Sill (2005) Sexual desire in later life, The
Journal of Sex Research, 42:2, 138-149
7. Schiavi, R., Stimmel, B., Mandeli, J., &Rayfield, E. (1993). Diabetes mellitus
and male sexual function: A control study. Diabetologia, 36, 745-751
8. Laumann EO, Das A, Waite LJ. Sexual dysfunction among older
adults: prevalence and risk factors from a nationally representative
U.S. probability sample of men and women 57–85 years of age. J Sex
Med.2008;5(10):2300–11.
9. Schiavi, R. (1999). Impact of medical illnesses on sexuality. In Aging and
Male Sexuality (pp. 124-146). Cambridge: Cambridge University Press
10. Avasthi A, Grover S, SathyanarayanaRao TS. Clinical Practice Guidelines
forManagement of Sexual Dysfunction. Indian J Psychiatry. 2017
Jan;59(Suppl1):S91-S115
11. Block J D. Create a Sexy Frame of Mind. Sex over 50. A Perigee Book,
published by the Penguin Group, USA 2008;Ch. 1:1-16
12. Kinsey,Pomeroy,Martin. Sexual behavior in human female.
Saunders,Philladelphia.1953
13. Kinsey,Pomeroy,Martin. Sexual behavior in human male.
Saunders,Philladelphia.1948
14. Pfeiffer.e.Sexuality and the ageing patient.R.Green.Human
sexuality; A health practitioners Text, 2nd Ed, Williama and Wilkins,
Ballitmore,1980;125-133.
15. Kolodny R C,W.H.Masters,V.E.Johnson.Textbook of sexual medicine.
Little,Brown,Boston 1979
16. Amore M, Di Donato P, Berti A, Palareti A, Chirico C, Papalini A, Zucchini
S. Sexual and psychological symptoms in the climacteric years. Maturitas.
2007 Mar 20;56(3):303-11.
17. Kruger T, Exton MS, Pawlak C, von zurMuhlen A, Hartmann U, Schedlowski
M. Neuroendocrine and cardiovascular response to sexual arousal and
orgasm in men.Psychoneuroendocrinology 1998;23:401-411.
18. Exton MS, Bindert A, Kruger T, Scheller F, Hartmann U, Schedlowski
M. Cardiovascular andendocrine alterations after masturbation-induced
orgasm in women. Psychosom Med1999;61:280-289.
19. Holly N T,. Evans G W,.BerlowtizD R, ChertowG M., ConroyM B, FoyC
G, GlasserS P, LewisC E, et al SPRINT Study Group; Antihypertensive
medications and sexual function in women: Baseline data from the
Systolic Blood Pressure Intervention Trial (SPRINT). J Hypertens. 2016
Jun;34(6):1224-31
20. Assari S; Intercourse avoidance among women with coronary artery
disease.J Sex Med. 2014 Jul;11(7):1709-16
21. Salavati A1, Mehrsai A1, Allameh F1, Alizadeh F1, Namdari F1,
Hosseinian M1, Salimi E1, Heidari F1, Pourmand G;Is Serum Uric Acid
Level Correlated with Erectile Dysfunction in Coronary Artery Disease
Patients?. Acta Med Iran. 2016 Mar;54(3):173-5
22. Al-Qudah Z, Yacoub H, SouayahN ;Disorders of the Autonomic Nervous
System after Hemispheric Cerebrovascular Disorders: An Update. J
VascInterv Neurol. 2015 Oct;8(4):43-52.
23. Jong-Ho Park, Bruce Ovbiagele and WuweiFeng; Stroke and sexual
dysfunction — A narrative review. Journal of the Neurological Sciences,
2015-03-15, Volume 350, Issue 1, Pages 7-13.
24. Pozo ME, Fang SH; Watch and wait approach to rectal cancer: A review.
World J Gastrointest Surg. 2015 Nov 27;7(11):306-12.
25. Hackett G, Krychman M, Baldwin D, Bennett N, El-Zawahry A, Graziottin
A, Lukasiewicz M, McVary K, Sato Y, Incrocci L; Coronary Heart Disease,
Diabetes, and Sexuality in Men. J Sex Med. 2016 Jun;13(6):887-904
26. Almeida PH, Castro Ferreira Cd, Kurizky PS, Muniz LF, Mota LM; How the
rheumatologist can guide the patient with rheumatoid arthritis on sexual
function. Rev Bras Reumatol. 2015 Sep-Oct;55(5):458-63.
27. Corona G, Isidori AM, Aversa A, Burnett AL, Maggi M ;Endocrinologic
Control of Men’s Sexual Desire and Arousal/ErectionJ Sex Med. 2016
Mar;13(3):317-37.
28. Shearer,M.R,Shearer.Sexuality and sexual counseling in the elderly.
ClinicalObstretics and Gynaecology.Vol 20,No 11977;197-208.
29. . Shiri, J. Koskimäki, J. Häkkinen et al., “Effects of age, comorbidity and
lifestyle factors on erectile function: Tampere Ageing Male Urological
Study (TAMUS),” European Urology, vol. 45, no. 5, pp. 628–633, 2004.
30. Rosen RC. Reproductive health problems in ageing men. Lancet 2005;
366: 183–185. Shiri R et al. Prevalence and severity of erectile dysfunction
in 50 to 75 year old Finnish men. J Urol 2003; 170: 2342–2344.
S408
31. Diagnostic and Statistical Manual of Mental Disorders:DSM-5. American
Psychiatric Publishing Washington DC 2013;5th Ed:423-460,685-706.
32. Hogan, Douglas R.The effectiveness of sex therapy: A review of literature.
In LoPicoloJoseph &LoPicolo Leslie (Eds). Handbook of sex therapy. New
York: Plenum Press 1978:57-84.
33. T.SSathyanarayanaRao, Shahajan Ismail, Darshan MS, AbhinavTandon;
Sexual disorders among elderly: An epidemiological study in south Indian
rural population; Indian Journal of Psychiatry; 57(3)2015; 236-241.
34. Shifran JL, Monz BU, Russo PA, et al. Sexual problems and distress in
United States women. Obs And Gyn 2008; 112(5): 970
35. BertschneiderJ,Macoy N. Sexual minterest and behavior in healthy 80-
102 years old.actions of sexual behavior.1988;17:109.
36. H. A. Feldman, I. Goldstein, D. G. Hatzichristou, R. J. Krane, and J. B.
McKinlay, “Impotence and its medical and psychosocial correlates: results
of the Massachusetts Male Aging Study,” The Journal of Urology, vol. 151,
no. 1, pp. 54–61, 1994.
37. G. Corona, D. M. Lee, G. Forti et al., “Age-related changes in general and
sexual health in middle-aged and older men: results from the European
Male Ageing Study (EMAS),” The Journal of Sexual Medicine, vol. 7, no.
4, pp. 1362–1380, 2010.
38. R. Shiri, J. Koskimäki, J. Häkkinen et al., “Effects of age, comorbidity
and lifestyle factors on erectile function: Tampere Ageing Male Urological
Study (TAMUS),” European Urology, vol. 45, no. 5, pp. 628–633, 2004.
39. Rosen RC. Reproductive health problems in ageing men. Lancet 2005;
366: 183–185. Shiri R et al. Prevalence and severity of erectile dysfunction
in 50 to 75 year old Finnish men. J Urol 2003; 170: 2342–2344.
40. George LK, Weiler SJ. Sexuality in middle and late life. Arch Gen
Psychiatry 1981; 38: 919.
41. Renshaw DC. Sex, intimacy and the older women. Women Health 1983;
8: 43.
42. Derogatis LR, Burnett AL. The epidemiology of sexual dysfunctions. J Sex
Med 2008;5(2):289.
43. Greendale GA, Hogan P, Shumaker S, et al. Sexual function in
Postmenopausal women: The Postmenopausal Estrogen/Progestin
Intervention (PEPI) trial. J Women Health 1996; 5: 445.
44. LeIblum, Sandra R, Koochaki , et al. Hypoactive sexual desire disorder
inpostmenopausalwomen : US Result from Women International Study of
health and sexuality (WISHeS). Menopause 2006; 13(1): 46
45. Shifran JL, Monz BU, Russo PA, et al. Sexual problems and distress in
United States women. Obs And Gyn 2008; 112(5): 970
46. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States:
prevalence and predictors. JAMA.1999;281(6):537-544.
47. Lindau ST, Schumm LP, Laumann EO, Levinson W, O’Muircheartaigh CA,
Waite LJ. A study of sexuality and health among older adults in the United
States. N Engl J Med. 2007;357(8):762-774.
48. . Chen LW, Chen MY, Chen KY, Lin HS, Chien CC, Yin HL.Topiramate-
associated sexual dysfunction: A systematic review. Epilepsy Behav. 2017
Jun 9;73:10-17.
49. Mahmoud A, Hayhurst KP, Drake RJ, Lewis SW. Second generation
antipsychotics improve sexual dysfunction in schizophrenia:A randomized
controlled trial. Schizophrenia Research and Treatment 2011; Article ID
596898, 6 pages.
50. Rosen RC, Lane RM, Menza M. Effects of SSRIs on sexual function: a
critical review. J ClinPsychopharmacol 1999;19:67-85.
51. Vester-Blokland ED, Van der Flier S, Rapid Study Group. Sexual
functioning of patients with major depression treated with mirtazapine
orally disintegrating tablet or sertraline. Program and abstracts of the
American Psychiatric Association 156th Annual Meeting; May 17-22,
2003; San Francisco, California. Abstract NR494.
52. G. Corona, D. M. Lee, G. Forti et al., “Age-related changes in general and
sexual health in middle-aged and older men: results from the European
Male Ageing Study (EMAS),” The Journal of Sexual Medicine, vol. 7, no.
4, pp. 1362–1380, 2010.
53. Sadock VA. Normal Human Sexuality and Sexual Dysfunctions. In:
Sadock BJ, Sadock VA, Ruiz P.Kaplan and Sadock’s Comprehensive
Textbook of Psychiatry. Ninth Edition. Lippincott Williams and Wilkins
2009;18.1a:2027-59.
54. Clayton AH, Hamilton DV. Female sexual dysfunction. Psychiatric Clin N
Am 2010; 33(2): 323.
55. AvasthiA& Banerjee ST. Guidebook on sex education. Marital and
Psychosexual Clinic, Department of Psychiatry, PGIMER, Chandigarh 2002.
56. Hogan, Douglas R.The effectiveness of sex therapy: A review of literature.
In LoPicoloJoseph &LoPicolo Leslie (Eds). Handbook of sex therapy. New
York: Plenum Press 1978:57-84.
57. Annon, Jack S. The behavioral treatment of sexual problems:Brief Therapy
New York Harper & Row 1976.
58. Kaplan HS. The new sex therapy: Active treatment of sexual dysfunctions.
New York: Brunner/ Mazel 1974.
59. Hawton K. The behavioral treatment of sexual dysfunction. British J
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]
Psychiatry1982;140:94-101.
60. Gholamine B,  Shafiei M,  Motevallian M,  Mahmoudian M.Effects of
pioglitazone on erectile dysfunction in sildenafil poor-responders: a
randomized, controlled study.J Pharm Pharm Sci. 2008;11(1):22-31.
61. Gasto´ N J. Rey-Valzacchi, Pablo R. Costanzo, Luis A. Finger, Alberto
O. Layus, Guillermo M. Gueglio, Leo´ N E. Litwak, pabloknoblovits.
Addition of metformin to sildenafil treatment for erectile dysfunction
in eugonadalnondiabetic men with insulin resistance. A prospective,
randomized, double-blind pilot study. Journal of andrology, vol. 33, no. 4,
july/august 2012
62. Min ChulCho,Jae-SeungPaick. Udenafil for the treatment of erectile
dysfunction.TherClin Risk Manag. 2014; 10: 341–354. Published online
2014 May 14. doi:  10.2147/TCRM.S39727.
63. Van Ahlen H., Piechota H.J., Kias H.J., Brennemann W., Klingmuller D.
Opiate antagonistsin erectile dysfunction: a possible new treatmentoption?
Results of a pilot study with Naltrexone.European Urology 1995;28:246-250
64. Padma-Nathan H. Efficacy and tolerability of Tadalafil, a novel
phosphodiesterase 5 inhibitor in treatment of erectile dysfunction.
American Journal of Cardiology 2003;92:19M-25M.
65. Bella A.J. & Brock G.B. Intracavernous Pharmacotherapy for erectile
dysfunction. Endocrine 2004;23:149-155.
66. Fink HA, MacDonald R, Rutks IR, Wilt TJ . Trazodone for erectile
dysfunction: a systemic review and meta-analysis. British Journal of
Urology International 2003;92:441-446.
67. Chen J., Mabjeesh N.J., Matkzin H., Greenstein A. Efficacy of sildenafil
as adjuvant therapy to selective serotonin reuptake inhibitor in alleviating
premature ejaculation. Urology 2003;61:197-200.
68. Linet OI &Ogrinc FG. Efficacy and safety of intracavernosalalprostadil in
men with erectile dysfunction.TheAlprostadil Study Group, New England
Journal of Medicine 1996;334:873-877.
69. Ghadiri MK, GorjiA.Review of Impotence: Natural remedies for impotence
in medieval Persia. International Journal of Impotence Research
2004;16:80-83.
70. Shelly TE, McInnis DO. Exposure to ginger root oil enhances mating
success of irradiated, mass-reared males of Mediterranean fruit fly
(Diptera: Tephritidae). J Econ Entomol 2001; 94: 1413–1418.
71. Qureshi S, Shah AH, Tariq M, Ageel AM. Studies on herbal aphrodisiacs
used in Arab system of medicine. Am J Chin Med 1989;17:57–63.
72. Kamtchouing P et al. Effects of Aframomummelegueta and Piper
guineenseon sexual behaviour of male rats. BehavPharmacol
2002;13:243–247.
73. Gonzales GF et al. Effect of Lepidiummeyenii (Maca), a root with
aphrodisiac and fertility-enhancing properties, on serum reproductive
hormone levels in adult healthy men. J Endocrinol 2003;176:
163–168.
74. Kashani L, Raisi F, Saroukhani S, et al. Saffron for treatment of fluoxetine-
induced sexual dysfunction in women: Randomized double-blind placebo-
controlled study. Hum PsychopharmacolClin Exp. 2012;28(1):54-60.
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Rao TSS et al: Management of Sexual disorders in Elderly
75. Aldemir M, Okulu E, Neselioglu S, Erel O, Kayigil O. Pistachio diet
improves erectile function parameters and serum lipid profiles in patients
with erectile dysfunction. Int J Impot Res. 2011;23(1):32-38.
76. T.SSathyanarayanaRao, Chittaranjan Andrade; Flibanserin: Approval
of a controversial drug for a controversial disorder: Indian Journal of
Psychiatry; 57(3)2015; 221-223.
77. SathyanaryanaRao T S, Gupta S, Tandon A. Intimacy Matters: Elderly
Sexuality. Indian Association for Geriatric Mental Health 2011:70-118.
78. L. M. Lothstein.The Aging Gender Dysphoria (Transsexual) Patient.
Archives of Sexual Behavior, VoL 8, No. 5, 1979.
79. Raphael J. Leo, Kye Y. Kim.Clomipramine Treatment of Paraphilias in
Elderly Demented Patients.Journal of Geriatric Psychiatry and Neurology
Vol 8, Issue 2, 123 – 124
80. Esther Sapire K; Contraception and Sexuality in Health and Disease;
McGraw-Hill Book Company (UK) Limited; 1990
81. T.S. SathyanarayanaRao; Psychobiology of love and sexual relationships
in elderly: Issue in management; Journal of Geriatric Mental Health: July-
Dec 2016; Vol.3(2); 91-99.
82. Defining sexual health Report of a technical consultation on sexual health
28–31 January 2002, Geneva WHO 2006.
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Clinical Practice Guideline on Management of Sleep Disorders in the

Elderly
Samir Kumar Praharaj1*, Ravi Gupta2, Navendu Gaur3
1
Department of Psychiatry, Kasturba Medical College, Manipal; 2Department of Psychiatry and Sleep Medicine, Himalayan
Institute of Medical Sciences, Doiwala, Dehradun; 3Director, Gaur Mental HealthClinic, Ajmer. *Correspondence:
samirpsyche@yahoo.co.in

Other Expert Participant: R K Solanki and reduced sensitivity to low to moderate light levels.
Among the elderly, core body temperature, and cortisol
INTRODUCTION and melatonin rhythms occur at an earlier time. The
changes in sleep that occur with age are summarized in
Sleep disorders are common in the elderly. It is estimated Table 1. However, these changes are not the common sleep
that 40-70% of elderly experience chronic sleep problems. complaints of the elderly population.
Higher rates of sleep problems are observed in those elderly
with medical and psychiatric comorbidity. The comorbid Indian Psychiatric Society (IPS) published Clinical Practice
disorders have additive effects on sleep disturbances, i.e. Guideline (CPG) for management of sleep disorders, for
higher the number of comorbidities, higher the rates of the first time in the year 2006 and a revised version in
sleep problems. the year 2017. The current version of the CPG is an
update of the earlier versions which specifically focuses
Elderly subjects have initial insomnia, wake up earlier on management of sleep disorders in the elderly. The
than usual, have higher time spent in bed, have nighttime current version of the CPG for sleep disorders in elderly
awakenings, nap more, and have decreased total sleep must be read in conjunction with the previous versions
as compared to younger adults. With increasing age of CPG for sleep disorders in the adult population.These
lighter stages of sleep becomes more, whereas, REM and guidelines provide a broad framework for assessment and
slow-wave sleep reduce; up to 6 years of age there is 2% management of sleep problems in elderly patients. Most of
decrease in slow-wave sleep every decade. Slow-wave sleep the recommendations made as part of the guidelines are
does not change much from 60 to 90 years of age. However, evidence-based. However, these guidelines should not be
sleep efficiency, i.e. the duration of sleep relative to total time considered as a substitute for professional knowledge and
in bed, continue to decrease over time. Sleep in the elderly clinical judgment. The recommendations made as part of
is fragmented, lighter and is characterized by episodes of these guidelines are best available options that have to be
arousals and awakenings. modified as per the clinical needs of the individual patient
and the treatment setting.
Certain changes in circadian physiology occur with
age. They include sleeping before the desirable sleep SLEEP DISORDERS IN ELDERLY
and wake times, earlier clock hour of internal circadian
time, alteration in the relationship between the internal Insomnia and daytime sleepiness are the common sleep
circadian time and sleep, reduction in circadian amplitude, complaints in older individuals (table 2). Among the elderly,
the prevalence of initial insomnia are found in 15%–45%,
Table 1: Sleep changes in the elderly middle insomnia in 20%–65%, late insomnia in 15%–54%, and
Sleep feature Change with age
10% have poor sleep quality.Those having sleep complaints
1. Total time spent in bed Increased report poor quality of life and higher rates of depression and
2. Total sleep time Decreased (5-7 hours/night)
3. Stage I sleep percentage Increased
anxiety. Cognitive deficits can appear because of chronic
4. Slow-wave sleep percentage Decreased sleep problems in the elderly that include attentional
5. REM Latency Decreased impairment, difficulties in short-term memory, increase
6. REM sleep percentage No change inresponse time and decreased performance. Furthermore,
7. Nocturnal arousals† Increased (average of 27 arousals/hour) sleep problems increase mortality in older individuals;
8. Sleep efficiency Decreased
9. Abnormal breathing episodes Increased
lower sleep efficiency (<80%) almost doubles the risk of
10. Leg movement episodes Increased all-cause mortality. The common primary sleep disorders
11. Sleep quality‡ Poor (non-restorative sleep) thatare seen in older adults include chronic insomnia
†
Defined according to EEG activity; ‡Subjective complaint disorder (CID), sleep-disordered breathing (SDB), restless

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Praharaj S K et al: Management of Sleep Disorders in Elderly

Table 2: Common sleep complaints in the elderly Table 4: Conditions are mistaken for insomnia
1.  Initial insomnia (difficulty falling asleep) Conditions Description
2.  Middle insomnia (nocturnal awakenings) Short sleepers Require 6 hours or less of nightly sleep
3.  Terminal insomnia (early morning awakening) Poor sleep hygiene Environmental factors
4.  Non-refreshing sleep (non-restorative sleep) Nocturia Nocturnal awakenings to void urine
5.  Daytime sleepiness Advanced sleep-wake phase Sleep early and wake up early
6.  Vivid dreams disorder
7.  Snoring, snorting Delayed Sleep-wake phase Sleep late and wake up late
8.  Creepy, crawly sensation in legs disorder
9.  Difficulty in concentration
10.  Memory problems
11. Fatigue
12. Irritability
Table 5: Insomnia in psychiatric disorders
Disorder Sleep changes PSG findings
Depression Sleep onset and Prolonged sleep latency, decreased
Table3: Diagnostic criteria for chronic insomnia maintenance sleep efficiency,short REM latency,
disorder insomnia, early increased percent REM sleep,
morning awakening increased REM density, decreased
Criteria (ICSD-3, DSM-5)
(hypersomnia in slow-wave sleep
1. Sleep initiation or maintenance problems (SOL or WASO more than 30
atypical depression)
minutes)
Bipolar Manic phase: decreased Longer sleep onset latency, poorer
2. Ample opportunities and circumstances to sleep
disorder sleep need (short sleep) sleep efficiency, reduced sleep
3. Daytime effects (e.g. irritability, fatigue, sleepiness, concentration Depressive phase: period time, increased percentage
difficulty) ‡ hypersomnia (40-80%) of stage 1 sleep, shortened REM
4. Duration of 3 months and frequency 3 per week† or insomnia latency, and increased REM
5. Symptoms are not due to another sleep disorder (e.g. pain disorder) density
SOL: sleep onset latency, WASO: wake after sleep onset;†These cut-offs are Anxiety Initial insomnia, Increased sleep latency, decreased
arbitrary; ‡Only in ICSD-3
disorder ruminations sleep efficiency, increased stage
N1 and N2 sleep, decreased slow-
legs syndrome(RLS)/periodic limb movements in sleep wave sleep, decreased REM sleep,
shortened total sleep time
(PLMS), REM sleep behavior disorder (RBD) and advanced
Schizophrenia Sleep onset and Prolonged sleep latency, decreased
sleep-wake phase disorder (ASWPD). maintenance insomnia sleep efficiency, poor subjective
sleep quality, shorter total sleep
CHRONIC INSOMNIA DISORDER time, and disrupted circadian
rhythmicity
Substance use Sleep onset and Alcohol withdrawal: increased N1
Insomnia is commonly defined as recurring problems in disorder maintenance insomnia sleep, decreased slow-wave sleep,
sleep initiation (sleep onset insomnia) or maintaining asleep shortened REM latency, increased
(sleep maintenance insomnia). The former is also called initial REM sleep percent
insomnia, and the later can be either middle or terminal
insomnia. Without distinguishing between primary and
secondary, ICSD-3 identifies insomnia disorder, that can Table 6: Medical conditions associated with insomnia in
be divided on the basis of its duration into transient or elderly
short-term (lasting only a few days to three to four weeks) Medical conditions
or chronic (persisting for more thanthree months). Clinically Cardiovascular Arrhythmia, Congestive cardiac failure, Myocardial infarction
(as well as using polysomnographic criteria) insomnia Pulmonary Chronic obstructive pulmonary disease, Asthma
Neurological Dementia, Stroke, Brain injury
is defined as a sleep latency of more than 30 minutes, Endocrine Type 2 Diabetes mellitus, Hypothyroidism
remaining awake after sleep onset formore than 30 Musculoskeletal Osteoarthritis, Fibromyalgia, Kyphosis
minutes, sleep efficiency of less than 85%, or less than 6 Urological Benign prostatic hyperplasia, Prostate cancer
to 6.5 hours total time asleep, occurring on three nights Renal Chronic kidney disease, End-stage renal disease
Gastrointestinal Gastroesophageal reflux disease, Irritable bowel syndrome
per week or more.Complaints of only non-restorative sleep
Other Cancer, Menopause, Bruxism
are no longer sufficient to diagnose insomnia disorder.
The diagnostic criteria for chronic insomnia disorder are
in table 3. and impairment in functioning. Other consequences of
untreated insomnia disorder include increased chances of
Insomnia is the most common sleep complaint in the developing mental illness, accidents, poorer quality of life,
elderly. Insomnia is seen in 20 to 40% of older adults as and greater healthcare utilization.
compared with 9% to 15% in the general adult population.
Sleep maintenance insomnia is more common in elderly Assessment and Evaluation
than sleep onset insomnia. Insomnia disorder leads to In the diagnostic evaluation of patients presenting with
fatigue, mood changes, poor cognition, daytime sleepiness insomnia, detailed sleep, medical and psychiatric history is

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Praharaj S K et al: Management of Sleep Disorders in Elderly

Table 7: Medications associated with insomnia

Type Medications
Antidepressants SSRIs (Fluoxetine), SNRI (Venlafaxine), Bupropion,
MAOI
Antipsychotics Aripiprazole
Stimulants Methylphenidate, Modafinil, Caffeine, Amphetamine
Antihypertensives Beta blockers, Amlodipine, Diltiazem, Verapamil,
Methyldopa
Bronchodilators Theophylline, albuterol
Corticosteroids Prednisone, Dexamethasone
Decongestants Pseudoephedrine, Phenylephrine, Phenylpropanolamine

Table 8: Objective assessment scales in insomnia

Figure 1: Algorithm for diagnosis of insomnia disorder
essential. Detailed information has to be obtained regarding
the initiation of symptoms, its course, and progression. Also,
information from the bedpartner is invaluable in arriving
at the correct diagnosis. There are several conditions that
can be mistaken for insomnia and need to be ruled out
before making a diagnosis of insomnia (table 4). Insomnia
is associated with several psychiatric disorders (table 5)
and medical disorders (table 6) in the elderly. It is pertinent
to ask about the prescription as well as non-prescription
medications that a person is taking several classes of
medications are associated with insomnia (table 7). Sleep log
or diary is a primary subjective method which gives nightly
information on perceived sleep patterns and quality. It not
only aids in the assessment of insomnia but also in monitoring
treatment outcomes. Simple forms of sleep diaries may only
include information on how much time a person spends in
bed, approximate durations of sleeping and waking time, and
estimation of sleep efficiency. While starting therapy, sleep
diaries are typically filled two weeks prior and continued
during treatment and follow up period. An algorithm for the
diagnosis of insomnia disorder is presented in figure 1.
There are specific scales and other rating instruments available
for assessment of sleep and insomnia symptoms (table 8). These
instruments aid in the evaluation of patients with insomnia and
may be used in addition to history and examination. Objective
methods such as polysomnography (PSG) and actigraphy are
used in special laboratories for measuring sleep initiation
and maintenance variables. PSG is not indicated routinely in the
evaluation of insomnia but may be used to rule out other sleep
disorders or in non-responders (i.e. when patients do not respond
to the first-line medications). Actigraphy is a small device that is
worn as a wristwatch that records movement frequency and is
a reliable and valid tool for assessing sleep duration.
Scale Description
Insomnia severity A 7-item instrument to measure the severity
index (ISI) of insomnia.Scores 0-7 is no insomnia, 8-14
subthreshold insomnia, 15-21 clinical insomnia –
moderate, and 22-28 clinical insomnia – severe.
Hindi version is available.
Pittsburgh Sleep A 19-item scale with seven subscales (subjective
Quality Index (PSQI) sleep quality, sleep latency, sleep duration, habitual
sleep disturbances, use of sleep medication and
daytime dysfunction); each of which is rated
from 0–3. Higher scores reflect more severe sleep
complaints.
Epworth Sleepiness A self-rated questionnaire with 8-items that assesses
Scale (ESS) the chances of falling asleep or dozing off while
doing eight different activities. It is rated on a
4-point scale (0-3) and the total score can range from
0 to 24. Higher ESS score denotes the average sleep
propensity in daily life, i.e. daytime sleepiness.
Dysfunctional Beliefs A self-rated instrument with 28 items that measure
and Attitudesabout negative cognitions about sleep. A Hindi version,
Sleep Questionnaire DBAS-16 is available.
(DBASQ)
Table 9: Non-pharmacological treatment for chronic
insomnia disorder
Treatment Description
1 Sleep hygiene education Diet, exercise, environmental factors
2 Stimulus control To establish a regular pattern of sleep and
maintain its association with the bed and
bedroom (e.g. only go to sleep when tired)
3 Sleep restriction Restricting the time spent in bed to sleep time,
and increasing gradually as sleep efficiency
improves
4 Relaxation training Training to decrease bodily tension, control
thought patterns that disturbs sleep
5 Cognitive behavioral Using both cognitive and behavioral techniques
therapy for insomnia such as stimulus control, sleep restriction and
relaxation training
6 Multicomponent therapy Using a combination of behavioral approaches
or brief behavioral without cognitive therapy
therapy for insomnia
Non-pharmacological management
The initial treatment for insomnia in the elderly should
include non-pharmacological approaches. Several
treatment options for the older individuals are available
(see Table 9).

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Praharaj S K et al: Management of Sleep Disorders in Elderly

Sleep hygiene education can be used which includes
certain lifestyle changes such as diet control, regular
exercise and reducing stimulant and alcohol use, in
addition to controlling environmental factors such as
ambient noise, light, and temperature that may disturb
sleep. Also, it is advised to avoid frequent daytime
napping, late evening exercises, and late heavy dinner.
A regular exercise regimen and adequate light exposure
during daytime have been found useful forinsomnia in
elderly.
Stimulus Control Therapy: The theory behind stimulus
control treatment is maladaptive conditioning between
the bedroom environment and bedtime with behaviors that are
incompatible with sleep. These behaviors include worrying,
reading, using a smartphone or watching TV while in bed.
Stimulus control aims at reducing the association between
these maladaptive behaviors which maintain arousal
during bedtime and increasing the association between
sleep and sleep-promoting stimuli. This is achieved by
restricting the time one is awake in bed by reducing the
sleep-interfering activities, and by maintaining a regular
sleep-wake schedule. Instructions to patients for stimulus
control include:1) Lie on the bed only when feeling sleepy,
2) Avoid any activity that keeps you awake in the bedroom,
other than sex, 3) Sleep only on bed in the bedroom, and
not on other places such as sofa, 4) To leave the bedroom
soon after waking, 5) To come to bedroom only when feel
sleepy, 6) Keep the waking up time fixed, irrespective of
the hours of sleep during night, and 7) Avoid napping
during day.
Cognitive behavioral therapy for insomnia (CBT-I): This has
been specifically developed for insomnia that comprises
of cognitive approaches that target cognitive distortions
and misconceptions related to insomnia, behavioral
approaches such as stimulus control and sleep restriction,
and educational approaches such as sleep hygiene. This
can be delivered in several different formats either face-
to-face individual or in a group setting, through the
telephone- or internet-based modules, and also through
self-help books. CBT-I in elderly has mild effect for
sleep problems and works best for sleep maintenance
insomnia. Multi-component therapy involves a different
combination of all the treatment approaches listed
above. Brief behavioral therapy (BBT) is also used for
insomnia in older adults.
Pharmacological management
In the elderly, the ideal hypnotic should 1) be able
to induce sleep rapidly, 2) have no adverse effects
on normal sleep architecture, 3) demonstrate no
significant residual effects, 4) be safe in patients with
respiratory and cardiac conditions, 5) have minimal
effects on memory, 6) not impair functioning, 7) have
no risk of tolerance or rebound insomnia, 8) be safe
during overdose, and 9) possess no potential for abuse
or dependence. However, there is no ideal hypnotic
available till date.
The basic rules of rational pharmacotherapy for insomnia
in the elderly includes prescribing the lowest effective dose
(which is usually half of adult dose), for shortest possible
time (no more than 3–4 weeks), intermittent dosing (two

Sleep Restriction: It includes reducing the duration spent

in bed to the actual time asleep, thus creating sleep Table10: First line medications† for chronic insomnia in
deprivation and subsequent increase in sleep drive. Before elderly
starting sleep restriction therapy, a sleep log for 2 weeks Non- Dose Half- Comment
is maintained which gives an estimate of average sleep benzodiazepines (mg) life (in
time versus actual time in bed, i.e. sleep efficiency (SE). (Z-drugs)* hours)

The allowed sleep time is the average subjective sleep time 1 Zaleplon 5-10 1-1.5 Sleep-onset insomnia, can be given
on waking during night
but is never less than 5 hours. As SE improves (more than 2 Zolpidem 5-10 1.5-2.6 Sleep-onset insomnia
90%), time in bed is increasedby 15-minute increments until 3 Zolpidem 6.25-12.5 2.8 Sleep-maintenance insomnia
adequate sleep duration is attained. controlled release
4 Zopiclone 3.75-7.5 2.5 Sleep-maintenance insomnia
Relaxation therapy and imagery: Thoughts can be detrimental 5 Eszopiclone 1-2 6 Sleep-maintenance insomnia
Melatonin agonists
to sleep and anxiety may cause sleep onset insomnia. 1 Melatonin‡ 1.5-6 0.5 Sleep-onset insomnia
Relaxation training originally used to alleviate anxiety is 2 Ramelteon 8 1-2.6 Sleep-onset insomnia
used for the treatment of sleep onset insomnia. Several 3 Agomelatine‡ 25 2.3 Sleep-onset and maintenance
techniques have been used in the treatment of insomnia insomnia
Orexin antagonist
that includes 1) Progressive muscle relaxation, 2) Autogenic
1 Suvorexant 10-20 12 Sleep-onset and maintenance
training (induction of sensations of warmth and heaviness insomnia
are used to promote somatic relaxation), 3) Imagery Histamine
(pleasant imagery can be used along with relaxation to antagonist
improve sleep). Individuals must practice the chosen 1 Doxepin 3-6 15 Sleep-maintenance insomnia
†
All benzodiazepines are included in the Beers List (potentially inappropriate
technique at least twice a day, and itmay require several medication use in older adults); ‡Evidence for efficacy in elderly is lacking;
weeks of practice before the skill is acquired. *Evidence for efficacy up to 1 year

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to four times weekly) if possible, using drugs that have
shorter elimination half-lives and lesser daytime sedation,
and which can be gradually discontinued without causing
rebound insomnia.
The first line drugsfor chronic insomnia disorder includes
nonbenzodiazepine Z-drugs, benzodiazepines and
melatonin receptor agonist ramelteon (table 10).Other
medications include orexin receptor antagonist suvorexant,
the antidepressants such as doxepin, antihistamines,
antipsychotics, and melatonin. There is no evidence
of superior efficacy of either of the agents in insomnia
treatment.
Non-benzodiazepine benzodiazepine receptor agonists:
The Z-drugs in this group include zolpidem, zaleplon,
zopiclone, and eszopiclone. These medications target
the GABA-A receptor complexes and have preferential
affinity for the α-1 subunit. For sleep onset insomnia,
medications with a shorter half-life (zaleplon or zolpidem)
are preferred, whereas, for sleep maintenance insomnia,
those with a longer half-life (zolpidem sustained release
or eszopiclone) are needed. Zaleplon can be used
specifically for the treatment of mid-night awakenings
because of its short half-life and ensures 4 hours of sleep.
Owing to less adverse effects, Z-drugs are considered
as the first-line agents for chronic insomnia wherever
available.
Melatonin agonists: Ramelteon, a selective melatonin MT1
and MT2 receptor agonist, has been used for chronic
insomnia at 4 to 8 mg/day. It probably acts through
suprachiasmatic nucleus by influencing homeostatic sleep
signaling. Ramelteon reduces sleep onset latency and total
sleep timein older adults with insomnia and wastolerated
well up to one year. Studies suggest that low doses of
melatonin (0.5-6 mg) improve initial sleep quality in older
adults with insomnia. There is some evidence to suggest
that agomelatine at 25 mg isuseful for the treatment of
insomnia in the elderly.
Orexin receptor antagonist: Suvorexant is a newer medication
for treating insomnia that blocks orexin-mediated wake
signaling. It improves initial and maintenance insomnia at
10-20 mg dosage. Suvorexant is usually taken on an empty
stomach so that sleep onset is faster. It is recommended
that it is taken at a time when one plans to sleep for at
least 7 hours continuously. Common side effects include
somnolence, fatigue, and headache. Suvorexant improves
sleep onset and maintenance and is tolerated well bythe
elderly.
Very low dose doxepin: Doxepin 3-6 mg through its H1
antagonism action has been found to be safe and effective
in the treatment of sleep maintenance insomnia in the
elderly. It improves sleep maintenance, total sleep time and
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Praharaj S K et al: Management of Sleep Disorders in Elderly
sleep quality, but has no effect on sleep onset. There are
no residual symptoms the next day. However, long-term
studies are lacking.
Several benzodiazepines such as estazolam, temazepam,
triazolam, flurazepam have been used for the treatment of
chronic insomnia. In absence of benzodiazepines approved
as hypnotics, other agents such as lorazepam, oxazepam,
clonazepam or diazepam can be used. The strategy is to use
long-acting benzodiazepines if comorbid anxiety is present.
In other situations, either short- or intermediate-acting
agent are preferred for sleep onset and sleep maintenance
insomnia, respectively. However, benzodiazepines should
be used with caution in the elderly, as it can lead to falls
and fractures, motor vehicle accidents, cognitive decline,
delirium, dependence and are best avoided if possible.
Sedating tricyclic antidepressants may be used as hypnotics
in low doses, e.g. amitriptyline 10-50 mg, imipramine 25-
50 mg. Other commonly used medication for insomnia,
mostly available as over-the-counter agents includes
diphenhydramine (50-100 mg) and promethazine (25-100
mg). However, these medications are best avoided in elderly
and are included in Beers list for potentially inappropriate
medication use in the elderly.
Trazodone 50 mg improves sleep parameters in Alzheimer’s
disease and is tolerated well. Mirtazapine (7.5-15 mg)
and esmirtazapine (1.5-4.5 mg) has also been reported
to be effective in the treatment of insomnia. Atypical
antipsychotics such as a low dose of quetiapine (25-100
mg) may be useful in some patients with insomnia if other
agents are not effective. Tiagabine, a selective inhibitor of
GABA transporter, at 4-6 mg dose increase slow-wave sleep
and was well tolerated in elderly. Gabapentin (100-600 mg)
and pregabalin (150-300 mg) may sometimes be used for
insomnia, specifically for those with comorbid neuropathic
pain symptoms.
SLEEP-DISORDERED BREATHING (SDB)
SDB is an umbrella term encompassing obstructive sleep
apnoea (OSA), primary or secondary centralsleep apnoea
(CSA), high-altitude periodic breathing, Cheyne–Stokes
respiration, nonobstructive hypoventilation, or hypoxemia
disorders secondary to pulmonary parenchymal, vascular,
neuromuscularor chest wall disorders. OSA, which is
the most common SDB, is characterized by a distinctive
snoring pattern caused by intermittent airway collapse.
In this condition, there are of periods of loud snoring or
brief gasping followed by cessation of respiration lasting
20 to 30 seconds. This leads to sleep arousals, possibly
due to arterial oxygen desaturation. Often the patient is
not aware of his or her snoring and nighttime arousals,
and a subset of patients complain of excessive daytime
sleepiness (EDS).
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Praharaj S K et al: Management of Sleep Disorders in Elderly
In patients having SDB, apneas (complete cessation of
respiration) and/or hypopneas (30% reduction in airflow
with 4% oxygen desaturation) occur during sleep. SBD is
diagnosed when these episodes last more than 10 sec and
occurseveral times during the night, leading to frequent
arousals and fall in oxygen saturation. The total number of
apnoea and hypopnea episodes per hour of sleep is known
asapnea-hypopnea index (AHI). For the diagnosis of SBD, an
AHI morethan 5 is required. SDB in > 65-year-olds is found
in >20%(as defined by AHI ≥10) and can be up to 60% in
frail elderly patients (Netzer et al. 2016). The known risk
factors for SDB in older adults include male gender, positive
family history, smoking, several craniofacial abnormalities
such as retrognathia, retrusion of the maxilla, macroglossia,
central obesity, concomitant pulmonary diseases that
reduce the chest wall compliance or any condition reducing
diaphragmatic movement. Therisk of SBD becomes more
if there is alcohol consumption sedating medication use.
In elderly patients with severe SDB (AHI≥30), cognitive
impairments are frequent that includes poor attention and
recall, slowed response time and impairments in executive
function.
Central sleep apnea (CSA) is characterized by loss of
ventilatory drive leading to stoppage of breathing (at least
5 or more per hour) during sleep. On the basis of etiology,
CSA in the older population can be broadly classified as
primary CSA, Cheyne–Stokes breathing pattern inheart
failure, and CSA in neurodegenerative disease and stroke.
Assessment and Evaluation
Evaluation of SDB includes a complete sleep history that
covers the history of snoring, snorting, non-refreshing sleep,
nocturia >2/night, nocturnal gastro-esophageal reflux,
sleep-talking, increased dreaming, daytime fatigue and in a
subset of patients, excessive daytime sleepiness. Preferably,
in all cases, parallel information must be obtained from bed-
partners who complain of witnessed pauses in breath during
sleep. Also, details of medical and psychiatric disorders,
prescribed medications, alcohol use, as well as cognitive
impairment should be elicited. Formal evaluation for OSA
should be considered in elderly patients who exhibit typical
symptoms, but also should be considered in patients with
comorbid cardiovascular risk factors or atypical symptoms
such as nocturia, un explainedfalls, automobile accidents,
or cognitive decline.
Findings on physical examination that supports OSA
include: 1) neck circumference >40 cm in males and 37
cm in females, measured at cricothyroid level, 2) body
mass index (BMI) >25 kg/mm2, 3) low-lying soft palate,
4) elongated or large uvula, 5) large tongue (often noted
by the presence of tongue edge crenations), or 6) large
tonsils or narrow distance between the tonsillar pillars.
In older adults, an additional risk factor is an edentulous
state, i.e. when patients remove their dentures at night,
S388
this leads to a reduction in the vertical dimension that
increases the occurrence of upper airway obstructive
events.
Screening tools, such as the Berlin Questionnaire can be
used for estimation of OSA risk, which has been validated
for Indian population. Epworth Sleepiness Scale may be
used to document sleepiness.
The SDB is diagnosed based on overnight sleep recording,
i.e. nocturnal PSG. A full night polysomnography in the
sleep laboratory is considered as the gold standard
method for diagnosis of SDB. In this method, sleep data
of entire night is recorded and is scored by a trained
scorer. The subsequent night is used to manually titrate
the pressure of PAP device. Thus, each study requires at
least two nights. However, in extreme cases where pre-
test clinical data suggests severe OSA and patient is not
having any other comorbidity, split-night study may be
done. During “split study” the initial half of the night is
used for diagnosis, whereas, the second half is used to
titrate positive arterial pressure (PAP) if the OSA is severe.
The limited-channel home-based testing (respiratory
polygraphy) has also been studied in making the
diagnosisof SDB. However, this must be used cautiously
only in selected cases as it provides data only regarding
sleep discorded breathing and can miss other information
which may be important for patient’s management.
Non-pharmacological management
Treatments for SDB depend on the symptoms and disease
severity, and the presence of cardiovascularor metabolic
disease. Treatment options in OSA are summarized in
table 11. Treatment for mild OSA (AHI 6-15) without any
other medical comorbidity includes lifestyle modification
strategies such as regular exercise and weightloss,
smoking cessation and reducing caffeine, alcohol, and
avoiding the use of sedatives and other recreational
drugs, and optimizing sleep and medical management of
comorbidities. These patients should be followed up every
three months to clinically assess symptoms and progress of
weight reduction.
Inmild-to-moderate SDB, positional measures and oral
mandibular advancement splints are used. Positional
therapy consists of techniques intended to increase the
time spent in the lateral sleeping position as opposed to
the supine position. These include using pillows to prop
up while lying or even sewing a ball into the back of the
shirt to make the supine position more uncomfortable.
There are sleep shirts available to facilitate lateral positional
therapy. Positional therapy is indicated specifically for
positional sleep apnea. In a meta-analysis, both continuous
positive airway pressure (CPAP) and positional modification
techniques were effectivein reducing AHI in those with
positional OSA; however, the former was better.
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Table 11: Treatment options for OSA
First-line therapy Second-line therapy
AHI <5 No therapy unless
sleep is fragmented or
comorbid conditions
(e.g. hypertension)
AHI 5-15 Positional therapy
Weight loss
Oral appliance
CPAP
AHI >15 CPAP BiPAP
Auto-titrating PAP
UPPP
Oral therapy
Positional therapy
Weight loss
Nasal expiratory resistance device
Oral appliances are helpful in improving respiration and sleep
quality in patients with OSA. It is recommended that for
OSA in adults, a custom, titratable appliance is prescribed
in consultation with a qualified dentist. However, their
effectiveness in elderly is poorly studied.
In moderate to severe cases of OSA or symptomatic cases
(associated with other comorbidities) mainstay of therapy is
positive airway pressure devices and it is considered the gold
standard treatment. Usually, manual CPAP device is preferred.
Bilevel PAP device is advisable when the patient is not able to
tolerate CPAP pressure or when PAP pressure requirement is
beyond 20 cmH2O. In a network meta-analysis, CPAP was
found to the most effective treatment for OSA. Older
adults whoadhere to at least three months of CPAP
treatment show improvements in cognitive functions such
as psychomotor speed, executive functioning, and non-
verbal delayed recall. Auto-PAP has limited efficacy in the
management of OSA.
Surgical modifications of upper airwayinclude procedures such
as maxillomandibular advancement (MMA), laser-assisted
uvulopalatoplasty (LAUP), uvulopharyngopalatoplasty
(UPPP) and radiofrequency ablation (RFA). In a meta-
analysis, MMA resulted in improvements in the AHI,
whereas, pharyngeal surgeries had less consistent
outcomes. Several studies have found good results with
newer pharyngeal surgeries and multi-level techniques,
which needs replication. However, due to limited data,
recurrence rates falling close to 50%, surgical methods are
restricted to only a selected group of patients with major
anatomical issues and PAP failure.
Hypnotics and other sedating medications worsen SDB by
inducing or worsening OSA and CSA. These medications
should be avoided if SBD is suspected.
Sometimes, modafinil or armodafinil can be used if daytime
sleepiness persists in spite of compliance to PAP therapy.
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SLEEP-RELATED MOVEMENT DISORDERS
Sleep-related movement disordersinclude conditions that
have stereotyped movements that disrupt sleep. The common
presenting features are initial or maintenance insomnia. It
includes restless leg syndrome (RLS), periodic limb movement
disorder (PLMD) and REM sleep behavior disorder (RBD).
RESTLESS LEGS SYNDROME (RLS)
Restless legs syndrome (RLS) (also called Willis-Ekbom
disease) is featured by dysesthesia in the legs which are usually
described as bubbly or a “creepy and crawly” sensation, tingling,
tickling, just restlessness, stretching sensation in the leg
muscles that occurs during rest and is relieved by movement.
Indian data suggests that most of the patients adopt one
of the four strategies: moving legs, coming out of bed and
walking, asking somebody to massage their legs and tying a
rope on their legs. These complaints are almost always seen
at night. A number of conditions may be mistaken for RLS, so
they should be ruled out carefully, before diagnosing RLS.The
prevalence of RLS in >65-year-olds is 10-35%.
Certain medications are seen in those having RLS. These
are commonly seen in elderly, increasing the chances
of having RLS. These include iron deficiency, uremia,
neuropathies and cardiovascular disorders. Hence, these
disorders must be ruled out in all patients of RLS. Serum
ferritin level <50 μg/L has been found to correlate with
severe RLS symptoms in comparison with serum iron levels,
total iron binding capacity (TIBC) or transferrin saturation
percentage. The prevalence of RLS is typically between
15to 40% in patients with uremia. It affects hemodialysis,
as patients are required to lie still during the procedure.
There is some evidence to suggest that RLS is associated
with diabetic or alcoholic neuropathy and spinocerebellar
ataxia type 3.
Assessment and Evaluation
Diagnosis of RLS is purely clinical and depends upon the
information provided by the patient (table12). All the criteria
need to be met to diagnose RLS. Also, the RLS mimics
(table13) need to be differentiated. Additional supportive
criteria include treatment response with dopaminergic
agents (60-75%). Iron deficiency frequently coexists and
needs investigation. Low serum ferritin (<50 µg/L) is a
sensitive marker for iron deficiency. The recommended
investigations in elderly include hemogram, serum ferritin,
blood urea and serum creatinine in all cases, and if possible,
serum folate, vitamin B12, and magnesium levels.
Salient features of patient workup have been summarized
in table 14.
International Restless Legs Scale (IRLS) is a 10-item measure
of disease severity in RLS that is easy to use and has
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been used extensively. Actigraphy or polysomnographic over-the-counter medications such as antihistamines worsen
assessment is usually not required. RLS symptoms and are better avoided. Other medications
such as antipsychotics, antiemetics, antidepressants, beta
The Suggested Immobilization Test (SIT) was developed for blockers, some anticonvulsants and lithium are known to
evaluation of RLS, however, it has limited clinical utility. In exacerbate RLS and should be discontinued if possible.
the standard procedure of the SIT, the patient lies down
with legs straight for one hour starting at 9pm. Patients are Pharmacological Treatment
encouraged to resist any urge to move during the SIT. Also, Pharmacotherapy is indicated when RLS symptoms impair
the SIT gives information on the propensity to symptom functioning, sleep, and quality of life. The medication options
onset because immobilization provokes RLS symptoms. A
modification of SIT, Multiple Suggested Immobilization Test Table 14: Work up of a suspected case of RLS at
(m-SIT) is also validated which consists of several tests in baseline and on each follow-up visit
the afternoon and evening hours.
History Symptom profile according to diagnostic criteria
Time of onset of symptoms
Non-pharmacological Treatment Duration of symptoms
Several dietary and lifestyle modifications are useful to Frequency of symptoms
control RLS. Patients are instructed to take a hot shower or Diurnal variability of symptoms
Topography of symptoms
massage their legs before bedtime, have regular sleeping
Disturbance in the nighttime sleep because of symptoms
and waking timings, regular exercise, and avoiding sleep Daytime consequences of the symptoms: cognitive,
deprivation and caffeine, cigarettes, andalcohol. Several emotional, social and occupational
Lifestyle of the patient: Caffeine use, sleep schedule, use of
psychoactive agents, physical activity during the day
Table12: Diagnostic Criteria for RLS/WED Other Any other medical disorder e.g., stroke, CAD, kidney disease,
Criteria† Comment medical hepatitis, cirrhosis, melena, BPH, hypertension, diabetes,
disorders rheumatoid arthritis, Parkinson’s disease
1 Urge to move the legs ± unpleasant Painful in 30-50% patients. Can
Treatment Other medications that the person is taking, especially
sensation in legs (Dysesthesia of also involve other body parts, but
Psychotropics
legs) predominantly in legs
Examination Local examination of leg, rule out pedal edema, varicose
2 Starts or worsens when one is Sensory symptoms are prominent
veins, arthritis, muscle weakness
inactive or at rest (Quiscegence) during SIT
Laboratory Complete Hemogram
3 Partial improvement by rest, till activity At least some symptomatic relief is
work-up S Ferritin
continues (Movement responsive) seen as soon as activity starts
BUN
4 Only occur or worsens during Ascertain circadian differences in
S Creatinine
evening or night (Nocturnal) response to symptoms to rest
5 Not because of any other medical or Differential diagnosis of RLS,
behavioral condition (RLS mimics) improves diagnostic specificity
†
International Restless Legs Syndrome Study Group (IRLSSG) 2012 revised Table 15: Pharmacotherapy of RLS
criteria; SIT: Suggested Immobilization Test; An easy to recall acronym URGE Drugs Dosing (mg/day)
(urge to move the legs, rest makes it worse, get up and go to make it better,
and evening and night times are worse) Non-ergotamine dopamine agonists
1 Pramipexole Start at 0.125 mg, titrate every 5-days, effectivedosage
0.125–0.75 mg 0.375-0.75 mg, maximum 1.5 mg
Table13: RLS Mimics 2 Ropinirole Start at 0.25 mg, titrate every 5-days, effectivedosage
1.5-2.5 mg, maximum 4 mg
Conditions Feature not consistent with RLS
3 Rotigotine 0.5-3 mg
1 Nocturnal leg cramps Cramping rather than urge to move reported, not Ergotamine dopamine agonists
worsened by rest 4 Pergolide† Start at 0.05mg, titrate by 0.05mg every 2 to3 days,
2 Positional discomfort Doesn’t occur in all rest positions, relief with effective dose 0.1 to 0.5mg, some require up to 1mg
single position change 5 Cabergoline† 0.5-2 mg
3 Habitual foot tapping Not nocturnal or quiescegenic, history of habit 6 Bromocriptine† Start at 1.25 to 2.5 mg, increase every 1-2 weeks, up to
present 5-15 mg
4 Neuropathy Symptoms localized to skin, not muscles, not Dopamine precursors
relieved by movement 1 Levodopa† 50-200 mg is effective, some may require up to 600 mg
5 Myalgia Not nocturnal or quiescegenic, worsened by Anticonvulsants
movement or after exertion 4 Gabapentin 600-1200 mg, maximum 2700 mg
6 Drug-induced Not focal on legs, starts after drug use 5 Pregabalin 150-450 mg
akathisia Carbamazepine 100-400 mg
7. Pacing associated History of worries/anxiety present. Symptoms not Opioids
with anxiety localized to legs 6 Oxycodone 2.5-15 mg
8. Burning feet Burning sensation reported in soles, no symptom 7 Methadone 5-40 mg
syndrome in calf muscles Other agents
9. Arthralgia in knees Patients complain of some “sensation” that is Clonazepam Improves sleep, nor PLMS. 0.5-2 mg is usual dose
limited to knee joint along with pain on movement; Clonidine 0.1-1 mg
improves by rest and worsens by movement †
Not preferred because of higher rates of augmentation

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Table 16: Max Planck Institute criteria for augmentation
A Basic features (all must be present)
1 Worsening of symptoms (5 days in past week)
2 Worsening of symptoms is not because of medical condition, change in
lifestyle orthe natural progression of the disorder
3 There is a previous positiveresponse to treatment
B Persisting paradoxical response to treatment
Worsening of symptoms after a dose increase and improves with dose
reduction
C Earlier onset of symptoms
1 Onset of symptoms at least four hours before, or
2 Earlier onset (between two and four hours) withone of the following:
a) Symptoms appear earlier during rest
b)Symptoms spread to other body areas
c)Symptoms are of higher intensity (or increase in periodic limb
movements if measured by polysomnography or thesuggested
immobilization test)
d)Relief with treatment is for shorter periods
Augmentation is diagnosed if A+B, A+C, or A+B+C criteria are present
Table 17: Plausible reasons for lower rates of RBD in
females
Reasons`
1. Milder forms of RBD in females
2. Less aggressive dreams
3. Feeling shy to share dream content or dream enactment behavior
4. Less observant bed-partner
5. No bed partner
6. Clinic/ hospital bias
in RLS are summarized in table 15. The first-line treatment
of primary RLS includes non-ergot based dopamine agonists
(ropinirole, pramipexole, and rotigotine), which have
the highest level of evidence for efficacy and safety. The
dopamine precursors (levodopa) and ergot-based dopamine
agonists (e.g. cabergoline) are effective, but more likely to
cause augmentation, hence, are considered as second-line
agents. In general, longer acting dopamine agents are
preferred and the dopaminergic load should be decreased by
prescribing the lowest dose that is effective for the shortest
time.
One of the major problem during treatment with short-
acting dopaminergic agents is augmentation, which is
characterized by either worsening of the severity of
symptomsor by an earlier onset of symptoms as compared
to baseline. This condition worsened by increasing the dose
of dopaminergic agents. This must be differentiated from
the end of dose phenomenon. The Max Planck Institute’s
operationalcriteria for augmentation is summarized in
table16.
If augmentation limits the use of dopamine agonists, non-
dopaminergic agents such as gabapentin and pregabalin
are preferred agents and have a fair level of evidence for
their efficacy. In some recent guidelines, use of these drugs
is considered as first-line to prevent the development of
augmentation. Specifically, gabapentin enacarbil (the pro-
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Praharaj S K et al: Management of Sleep Disorders in Elderly
drug of gabapentin) is preferred considering its longer
half-life. Use of opioids is limited by their possible abuse
potential but may be usefulin non-responders, specifically
those having severe augmentation features. Benzodiazepines
such as clonazepam do not reduce PLMS, but improves
sleep; therefore, they are indicated if sleep disturbance is
prominent.
For secondary RLS, the underlying condition needs
treatment along with specific treatment with dopamine
agonists. Iron therapy is indicated in those with lower
ferritin levels. Oral supplementation or intravenous
formulations are indicated so that the ferritin levels
increase to more than 50 μg/L.It is not effective if ferritin
levels are higher than 100 μg/L and anemia is absent. In
those with RLS associated with end-stage renal disease,
dialysis improves the symptoms.
RAPID EYE MOVEMENT SLEEP BEHAVIOR
DISORDER (RBD)
The prevalence of RBD is 0.5% in the general population.
Among the elderly, 7% have RBD. It is predominantly seen
in males after the age of 50 years. The plausible reasons for
lower rates in females are summarized in table 17.
RBD is featured by dream enactment behavior (DEB) that
ranges from simple to complex vocalizations and motoric
behaviors that occur during REM sleep. These behaviors
occur because there are periods where there is no loss
of muscle tone that is typically found in REM sleep, i.e.
REM sleep without atonia (RSWA). Typically, RBD behaviors
are more prominent during the latter part of the night
when REM sleep predominates. Common RBD behaviors
are walking, speaking and eating. Occasionally, they can
be violent and the patient or their bed partner may be
hurt; however, most are unaware of these actions. It is
likely that some patients with RBD involve impressive
and obvious DEB, whereas, most DEB may be unobtrusive
movements limited to the hands, otherwise known as hand
babbling.
Idiopathic RBD is linked to neurodegenerative disorders,
specifically with alpha-synucleinopathies (e.g. Parkinson’s
disease, Lewy Body Dementia, multiple system atrophy)
(see table 18). Features that suggest the possibility of
neurodegenerative disorders include abnormal smell or
vision, constipation, orthostasis and motor slowing. Several
medications and drugs are also associated with RBD (see
table 19).
Assessment and Evaluation
The observations of a bed partner or someone who
has witnessed the patient’s sleep are invaluable. In
patientswithout a bed partner, clues suggesting possible
RBD include vivid or terrifying dreams, falling out of bed,
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or unexplained nocturnal bruising. RBD can be accurately Non-pharmacological Treatment

identified with the following screening question: “Has The primary goals of treatment in RBD include preventing
anyone ever told that you act out your dreams (e.g. punching injury to the patient and their bed partner during sleep
or flailing arms in theair or screaming and shouting in your andminimizing sleep disruption.
sleep?)”. RBD need to be distinguished from NREM sleep
disorders. One clue which favors RBD is that patients are Injury-preventing techniques: These includes modification
alert and immediately have a vivid dream recall. Another clue of environment such as sleeping on the floor to avoid
is the phenomenon of isomorphism, i.e. the DEB correlates falling from bed, padding corners of furniture, keeping the
with a recalled dream, in contrast to confusion and little window and door locked at night and removing potentially
recall after NREM sleep disorder. A 16-item Mayo Sleep dangerous objects from the room. Using heavy curtains
Questionnaire (MSQ) can be used to screen for RBD and on bedroom windows reduces sleep disruption. The bed
other sleep disorders. All patients with dream enactment partner may be asked to sleep separately till the condition
history should be screened for OSA, which can mimic RBD. improves.
The differential diagnosis of RBD is summarized in table 20.
Detailed neurological examination in patients with RBD is
Discontinue medications known to exacerbate RBD: Medications
summarized in table 21. Early features of neurodegenerative
that are known to exacerbate RBD should be discontinued if
disorders having RBD is presented in table 22.
possible. These include antidepressants (selective serotonin
reuptake inhibitors, serotonin-norepinephrine reuptake
Although history may suggest RBD, PSG is often required
for definitive diagnosis. The diagnosis of RSWA is based inhibitors, tricyclic antidepressants and monoamine
on EMG findings during REM sleep. To diagnose RBD, EMG
abnormalities include increase in muscle tone and/or phase Table 20: Differential diagnosis of RBD in elderly
twitch during REM sleep. The duration of RBD may have a Disorders of arousal Others
wide variation, however, most occur less than once weekly Primary Secondary
and last for less than 2 minutes. · Sleep terror · Periodic limb · Physiologic
· Sleepwalking movement disorder hallucinations of sleep
Approach to a patient with RBD is depicted in figure 2. · Sleep talking · Obstructive sleep · Dissociative/
· Confusional apnoea conversion disorder
arousals · Gastroesophageal · Malingering
Table 18: Secondary causes of RBD reflux disease · Domestic violence
Degenerative Other · Nocturnal seizures · Post-traumatic stress
(e.g. frontal lobe disorder
1. α-synucleinopathies 5. Limbic Encephalitis
epilepsy) · Vertigo
· Multiple System Atrophy (MSA) 6. Epilepsy
· Absence seizures
· Dementia of Lewy Body (DLB) 7. Multiple sclerosis
· Epilepsy in mentally
· Parkinson’s disease (PD) 8. Guillain-Barre syndrome
retarded
· Pure autonomic failure (PAF) 9. Stroke
2. Tauopathies/Amyloidopathies 10. Brain tumors
· Progressive supranuclear palsy (PSP) 11. Obstructive sleep
· Guadeloupean Parkinsonism (GuadeP) apnoea (Pseudo-RBD)
Table 21: Neurological history and examination: salient
· Alzheimer’s disease (AD) 12. Medications
· Frontotemporal dementia (FTD) 13. Drug withdrawal features
· Corticobasalganglionic degeneration (CBGD) Prodrome of Explore for early Subtle signs on Triad* of
3. Spinocerebellar atrophy-3 (SCA-3) RBD bradykinesia neurological impending
4. Huntington’s disease examination neurodegeneration
· Twitching · Difficulty in · Affect · RBD with chronic
Table 19: Drugs associated with RBD · Simple turning over in · Voice volume unexplained
motor bed · Speed of · Hyposmia
Iatrogenic (or acute) Drug withdrawal movements · Slowing of eating articulation · Constipation
1. Antidepressants 1. Alcohol · Speaking or dressing · Blink rate · If impaired color
· Specific serotonin-reuptake inhibitors (SSRIs) 2. Benzodiazepines · Yelling · Above difficulties · Motor tone identification,
· Tricyclic antidepressants (TCAs) 3. Barbiturates unilateral/bilateral · Cogwheel rapid conversion
· Monoamine oxidase inhibitors (MAOIs) 4. Meprobamate significant of rigidity to PD
· Serotonin Noradrenergic Reuptake Inhibitors 5. Pentazocine Parkinson’s · Gait testing: · Psychiatric
(Venlafaxine) disease stride length, disorder
· Noradrenaline and Specific Serotonergic · Change of arm swing, (depression) may
Agent (Mirtazapine) handwriting freezing, be a predating
2. Cholinesterase inhibitors · Lowering of number of steps factor*
3. β-blockers speech volume to turn
4. Tramadol (intravenous) · Whether ever felt · Postural
5. Caffeine feet stuck to the instability
6. Chocolate floor

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Praharaj S K et al: Management of Sleep Disorders in Elderly

depression, bupropion is preferred as it doesn’t worsen

RBD.

Treat underlying cause: If any specific underlying cause is

found (e.g. brain stem tumor), it requires specific treatment.

Prognostic counseling: Patients need to be educated

regarding the possibility of RBD being an early marker of
neurodegenerative disease.

Bed alarm: A bed alarm can be used for the treatment of

RBD. It consists of a pressure sensor that is placed on the
shoulders which get activated during dream enactment. At
that time a pre-recorded message is played which tells them
that it is a dream, thereby calming the patient and they go
back to sleep.

Pharmacological Treatment
First-line treatment: The preferred treatment for RBD is
low-dose clonazepam at doses from 0.5-1 mg/day. It is a
long-acting benzodiazepine that reduces abnormal motor
behavior in 90% of subjects (table 23). However, there
are concerns regarding its use in elderly such as residual
sleepiness, unsteadiness leading to falls and fractures,
Figure 2: Flowchart showing differential diagnosis, progression delirium and cognitive impairment, which limits its
monitoring and treatment decision tree in idiopathic RBD use in frail patients. Also, it should be avoided in RBD
(iRBD) patients with comorbid OSA, as it is potential respiratory
suppressant. Furthermore, clonazepam being a cytochrome
Table 22: Early features of neurodegenerative disorders P450 substrate, drug interactions needs consideration.
that present as RBD
Disease Clinical features Investigation findings
Melatonin at high-doses is also as effective as clonazepam
for RBD and can be considered as an alternative first-line
Parkinson’s Older, male, non-tremor EEG slowing
disease (PD) motor PD, more severe PD, Baseline tonic, but not the agent. It is probably better tolerated, specifically in those
longer disease duration, phasic, EMG activity higher in with neurodegenerative disease. The recommended dose is
sleepier, autonomic RBD cases converting to PD 3-15 mg at bedtime (median effective dose is 6 mg). Other
dysfunction, fall, worse not DLB melatonergic agents such as agomelatine (25–50 mg) or
cognition & MCI, more Midbrain hyperechogenicity on
ramelteon (8 mg) at bedtime may be helpful, but evidence
hallucinations and transcranial sonography (absent
delusions, higher levodopa in narcolepsy with RBD) for their efficacy is low.
doses,
Dementia RBD+MCI indicate On neurocognitive testing, Second-line drugs: Medications such as dopaminergic
with Lewy evolving DLB. Fewer poor performance on attention, agonists (pramipexole) and acetylcholinesterase inhibitors
bodies fluctuations and visuoconstructional ability,
(rivastigmine) have been used with variable success in
hallucinations perceptual organization, visual
Reduced cardiac MIBG memory, and letter fluency patients with RBD and may be considered in treatment-
uptake is an early specific (AD group, perform worse on refractory patients as second-line agents. Other agents that
biomarker confrontation naming and verbal have been used include temazepam, lorazepam, zolpidem,
memory) zopiclone, cannabinoids, and sodium oxybate.
Multiple Early age at onset. Sleep Cardiac MIBG uptake within
System talking is an early feature normal limits
Atrophy of RBD. Female to male CIRCADIAN RHYTHM SLEEP-WAKE
ratio higher than other DISORDERS (CRSWD)
synucleinopathies
Progressive RBD appears concurrently Sleep and circadian rhythm changes with aging, as well
supranuclear or after onset of
palsy/ AD parkinsonism
as less exposure to light and reduced activity level, are
factors leading to circadian rhythm sleep-wake disorders
(CRSWDs) in the elderly (see table 24). Sleep quality is
oxidase inhibitors), beta-blockers (atenolol, bisoprolol), optimal if there is a match between the intended sleep
tramadol and cholinesterase inhibitors. If there is comorbid times with thetiming of endogenous circadian rhythm.

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CRSWDs can occur if the timings of central circadian Evaluation and assessment
clock changes or the timing of endogenous circadian To diagnose CRSWDs, clinical sleep history, monitoring
rhythm don’t match with the daily social and physical with a sleep diary, and if possible actigraphy for at least
environment.The underlying cause for CRSWDs is related one week is required. Patients with ASWPD typically
to circadian timing alterations, however, the clinical report sleepiness during the early evening, early sleep
presentation depends on the physiological, behavioral and onset (between 6-9 PM), and spontaneous early morning
environmental factors.Shift work and Jet lag disorder are awakening (2-5 AM). Even if they resist evening sleepiness
extrinsic, whereas, rest are intrinsic disorders. and sleep at conventional bedtime, they still wakeup early
and have daytime sleepiness. A sleep log or actigraphy
In the elderly advanced sleep-wake phase disorder monitoring is required to demonstrate a pattern of
(ASWPD) is most common, which is characterized by advancement in the regular sleep time for at least one week.
an advancement of the sleep-wake cycle. It presents as Psychiatric disorders that cause early morning awakening
regular and involuntary sleep and wake times which occur such as depression and bipolar disorder need to be ruled
several hours before the usual times. In a large multicenter out. Morningness-Eveningness Questionnaire (MEQ) can be
study on subjects more than 65 years, 20% experienced used to characterize the chronotype of an individual, which
early morning awakening. shows a definite ‘morning type’. Polysomnography is not
always needed for diagnosis of CRSD, but may be indicated
to rule out other comorbid conditions such as OSA or PLMS.
Table 23: Drugs used in treatment of RBD
If PSG is performed, it is to be done at the usual sleep time
Molecule t½ (hour) Dose Comments
(mg/d)
of the patient.
1 Clonazepam 30-40 0.25-4 1st line agent; suppresses
phasic REM activity To study the phase and amplitude of circadian rhythm,
2 Melatonin 0.33-0.83 3-12 2nd line agent; restores REM dim light melatonin onset (DLMO) and nadir core body
(dose/route sleep atonia; 30 min before temperature (Tmin) can be used. DLMO is considered
dependent) bedtime as the most reliable among all. It is the timewhen
3 Zopiclone 3.5-6.5 7.5 Inconclusive/mixed results
endogenous melatonin levels start rising in dim light, i.e.
4 Agomelatine 1-2 25-50
5 Ramelteon 2-5 8 approximately 2–3 hours before the usual bedtime. DLMO
6 Donepezil 70 5-10 is used to estimate the circadian timing of individual so
7 Rivastigmine 1-2 6-12 that melatonin and other treatment can be administered
8 Pramipexole 8-12 0.5-1.5 at appropriate times. The intrinsic circadian periodcan
9 L-dopa 0.83-1.5 250-1250
be estimated under free-running conditions, where the
10 Desipramine 24 50-300
11 Sodium Oxybate 0.5-1 2500-9000 effects of light are controlled.
12 Carbamazepine 12-17 400-1200
(repeated Management of Advanced sleep-wake phase disorder (ASWPD)
doses) Treatment of ASWPD involves delaying the sleep-wake
timing through chronotherapy, timed-melatonin, and timed-
light exposure. Sleep hygiene is not of much use, except for
Table24: Circadian rhythm sleep-wake disorders avoiding long evening naps which may improve nocturnal
Disorder Description sleep. The co-morbid conditions that may contribute to
1 Delayed sleep-wake Sleep is delayed at least by 2hours than usual sleep complaints, especially depression should be treated.
phase disorder along with a difficulty in falling asleep at the
(DSWPD) socially acceptable time. Uncommon in elderly.
2 Advanced sleep- Sleep occurs at least 2 hours prior to theusual
Nonpharmacological treatment
wake phase disorder times. Most common disorder in the elderly. Light therapy: The principle involves reducing morning light
(ASWPD) that advances phase and increasing evening light which
3 Irregular sleep-wake There is no clearly defined sleep-wake rhythm, delays phase. Patients are instructed to avoid going out and
rhythm disorder with variable sleep and wake episodes. Seen in stay in a dark room during the early morning and to wear
(ISWRD) elderly patients with dementia.
4 Non-24-Hour The circadian pacemaker is not synchronous with
sunglasses while going out. Also, they are instructed to
Sleep-Wake the light/dark cycle leading to either insomnia or remain outdoors in the late afternoon and early evening and
Disorder(N24SWD) excessive sleepiness, depending on when sleep is use bright lights inside the home during the evening. Bright
(Free-running disorder) attempted. Seen in blind individuals. light is recommended in the evening, between 7 to 9 PM
5 Shift work disorder Shifts in work schedules (e.g. night, early (at least 5000 lux for 2 hours) todelay the circadian phase.
morning or rotating) cause decrease in total
sleep time (typically by 1–4 hours) along with a
subjective feeling of unrefreshing sleep. Chronotherapy: The goal in the treatment of ASWPD is a
6 Jet lag disorder The timing of endogenous circadian rhythm correction of abnormal early sleep phase. Most patients
does not match with the time zone during long- have difficulty delaying their sleep schedule, but find it
distance travel.
easier to advance. Therefore, in some persons, advancing

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around the clock is preferred. In ASWPD, typically timing of
sleep is advanced by 3 hours every 2 days until the expected
time is reached. However, such schedules may not be liked
by many and can cause disruptions in routine work.
Pharmacological Treatment
Melatonin: Phase delay can be induced by administration
of melatonin in the early morning; the optimal time is in
the early morning following spontaneous awakening. Light
exposure should be minimized so that phase delay with
melatonin is not countered by the phase advance effect of
early morning light. It is useful at doses ranging from 0.5
to 10 mg.
CONCLUSION
Sleep in the elderly gets lighter and fragmented, however,
very few otherwise healthy older people complain about
their sleep problem. In the majority, sleep disruptions are
associated with medical and psychiatric disorders, use of
medications, changes in circadian rhythm and other sleep
disorders such as sleep disordered breathing and REM
behavior disorder. It is important to identify various causes
of sleep disturbances in the elderly and to start treatment
at the earliest. Furthermore, the factors that maintain
disrupted sleep are targeted using nonpharmacological and
behavioral techniques, along with medications if needed.
This would enhance the quality and duration of sleep, and
improve the overall quality of life in the elderly.
REFERENCES
1. Abbott SM, Reid KJ, Zee PC.Circadian Rhythm Sleep-Wake Disorders.
Psychiatr Clin North Am 2015;38(4):805-23.
2. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS,
Winkelman JW, et al; International Restless Legs Syndrome Study
Group.Restless legs syndrome/Willis-Ekbom disease diagnostic criteria:
updated International Restless Legs Syndrome Study Group (IRLSSG)
consensus criteria--history, rationale, description, and significance.Sleep
Med 2014;15(8):860-73.
3. Altınyazar V, Kiylioglu N.Insomnia and dementia: is agomelatine
treatment helpful? Case report and review of the literature. Ther Adv
Psychopharmacol 2016;6(4):263-8.
4. Barnes H, Edwards BA, Joosten SA, Naughton MT, Hamilton GS,
Dabscheck E.Positional modification techniques for supine obstructive
sleep apnea: A systematic review and meta-analysis. Sleep Med Rev
2016: S1087-0792(16)30138-1.
5. Camargos EF, Louzada LL, Quintas JL, Naves JO, Louzada FM, Nóbrega
OT.Trazodone improves sleep parameters in Alzheimer disease patients:
a randomized, double-blind, and placebo-controlled study.Am J Geriatr
Psychiatry 2014;22(12):1565-74.
6. Caples SM, Rowley JA, Prinsell JR, Pallanch JF, Elamin MB, Katz SG,
Harwick JD.Surgical modifications of the upper airway for obstructive
sleep apnea in adults: a systematic review and meta-analysis.Sleep
2010;33(10):1396-407.
7. Cheng SK, Dizon J.Computerised cognitive behavioural therapy for
insomnia: a systematic review and meta-analysis.Psychother Psychosom
2012;81(4):206-16.
8. Dhyani M, Rajput R, Gupta R.Hindi translation and validation of
dysfunctional beliefs and attitudes about sleep (DBAS - 16).Ind Psychiatry
J 2013;22(1):80-5.
9. García-Borreguero D, Allen RP, Kohnen R, Högl B, Trenkwalder C, Oertel
W, et al; International Restless Legs Syndrome Study Group.Diagnostic
standards for dopaminergic augmentation of restless legs syndrome:
report from a World Association of Sleep Medicine-International Restless
Legs Syndrome Study Group consensus conference at the Max Planck
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Praharaj S K et al: Management of Sleep Disorders in Elderly
Institute.Sleep Med 2007;8(5):520-30.
10. Garcia-Borreguero D, Cano-Pumarega I.New concepts in the management
of restless legs syndrome.BMJ 2017;356:j104.
11. Garcia-Borreguero D, Kohnen R, Boothby L, Tzonova D, Larrosa O, Dunkl
E.Validation of the multiple suggested immobilization test: a test for the
assessment of severity of restless legs syndrome (Willis-Ekbom disease).
Sleep 2013;36(7):1101-9.
12. Garcia-Borreguero D, Silber MH, Winkelman JW, Högl B, Bainbridge
J, Buchfuhrer M, et al.Guidelines for the first-line treatment of restless
legs syndrome/Willis-Ekbom disease, prevention and treatment of
dopaminergic augmentation: a combined task force of the IRLSSG,
EURLSSG, and the RLS-foundation.Sleep Med 2016;21:1-11.
13. Gupta R, Ahmad S, Dhar M, Goel D, Lahan V. Clinical presentation of
restless legs syndrome: does the gender matter? Sleep Biol Rhythms
2014a; 12: 180-186.
14. Gupta R, Ali R, Dhyani M, Das S, Pundir A. Hindi translation of Berlin
questionnaire and its validation as a screening instrument for obstructive
sleep apnea (OSA) J Neurosci Rural Practice 2016; 7: 244-249.
15. Gupta R, Das S, Gujar K, Mishra KK, Gaur N, Majid A.Clinical Practice
Guidelines for Sleep Disorders.Indian J Psychiatry. 2017 Jan;59(Suppl
1):S116-S138.
16. Gupta R, Goel D, Ahmed S, Dhar M, Lahan V. What patients do to
counteract the symptoms of Willis-Ekbom disease RLS/WED): Effect of
gender and severity of illness. Ann Indian Acad Neurol 2014b;17:405-8.
17. Hening WA, Allen RP, Earley CJ, Picchietti DL, Silber MH; Restless Legs
Syndrome Task Force of the Standards of Practice Committee of the
American Academy of Sleep Medicine.An update on thedopaminergic
treatment of restless legs syndrome andperiodic limb movement disorder.
Sleep 2004;27:560–83.
18. Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J,
et al.Suvorexant in elderly patients with insomnia: pooled analyses of data
from phase III randomized controlled clinical trials. Am J Geriatr Psychiatry
2017;25(7):791-802.
19. Horne JA, Ostberg O. A self-assessment questionnaire to
determinemorningness-eveningness in human circadian rhythms. Int
JChronobiol 1976;4:97–110.
20. Hornyak M, Feige B, Riemann D, Voderholzer U.Periodic leg movements
in sleep and periodic limb movement disorder: prevalence, clinical
significance and treatment.Sleep Med Rev 2006;10(3):169-77.
21. Johns MW.A new method for measuring daytime sleepiness: the Epworth
sleepiness scale.Sleep 1991;14(6):540-5.
22. Joshi S.Nonpharmacologic therapy for insomnia in the elderly.Clin Geriatr
Med 2008;24(1):107-19.
23. Jung Y, St Louis EK.Treatment of REM sleep behavior disorder.Curr Treat
Options Neurol 2016;18(11):50.
24. Keijzer H, Smits MG, Duffy JF, Curfs LM.Why the dim light melatonin onset
(DLMO) should be measured before treatment of patients with circadian
rhythm sleep disorders.Sleep Med Rev 2014;18(4):333-9.
25. Lahan V, Gupta R.Translation and validation of the insomnia severity
index in hindi language.Indian J Psychol Med 2011;33(2):172-6.
26. Lankford A, Rogowski R, Essink B, Ludington E, Heith Durrence H, Roth
T.Efficacy and safety of doxepin 6 mg in a four-week outpatient trial of
elderly adults with chronic primary insomnia. Sleep Med 2012;13(2):133-8.
27. Liu T, Li W, Zhou H, Wang Z.Verifying the relative efficacy between
continuous positive airway pressure therapy and its alternatives
for obstructive sleep apnea: a network meta-analysis.Front Neurol
2017;8:289. doi: 10.3389/fneur.2017.00289.
28. Markota M, Rummans TA, Bostwick JM, Lapid MI.Benzodiazepine use in
older adults: dangers, management, and alternative therapies. Mayo Clin
Proc 2016;91(11):1632-9.
29. McGrane IR, Leung JG, St Louis EK, Boeve BF.Melatonin therapy for
REM sleep behavior disorder: a critical review of evidence.Sleep Med
2015;16(1):19-26.
30. Michaud M, Paquet J, Lavigne G, Desautels A, Montplaisir J. Sleep laboratory
diagnosis of restless legs syndrome.Eur Neurol 2002;48(2):108-13.
31. Milligan SA, Chesson AL.Restless legs syndrome in the older adult:
diagnosis and management.Drugs Aging 2002;19(10):741-51.
32. Montgomery P, Dennis J.A systematic review of non-pharmacological
therapies for sleep problems in later life.Sleep Med Rev 2004;8(1):47-62.
33. Montgomery P, Dennis J.Cognitive behavioural interventions for
sleep problems in adults aged 60+.Cochrane Database Syst Rev
2003;(1):CD003161.
34. Netzer NC, Ancoli-Israel S, Bliwise DL, Fulda S, Roffe C, Almeida F, et
al.Principles of practice parameters for the treatment of sleep disordered
breathing in the elderly and frail elderly: the consensus of the International
Geriatric Sleep Medicine Task Force. Eur Respir J 2016;48(4):992-1018.
35. Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP.Using the Berlin
Questionnaire to identify patients at risk for the sleep apnea syndrome.
Ann Intern Med 1999;131(7):485-91.
36. Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV.Meta-analysis
S395
[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]
Praharaj S K et al: Management of Sleep Disorders in Elderly
of quantitative sleep parameters from childhood to old age in healthy
individuals: developing normative sleep values across the human lifespan.
Sleep 2004;27(7):1255-73.
37. Ohayon MM.Epidemiology of insomnia: what we know and what we still
need to learn.Sleep Med Rev 2002;6(2):97-111.
38. Olde Rikkert MG, Rigaud AS.Melatonin in elderly patients with insomnia.
A systematic review.Z Gerontol Geriatr 2001;34(6):491-7.
39. Patel KV, Aspesi AV, Evoy KE.Suvorexant: a dual orexin receptor
antagonist for the treatment of sleep onset and sleep maintenance
insomnia.Ann Pharmacother 2015;49(4):477-83.
40. Ramar K, Dort LC, Katz SG, Lettieri CJ, Harrod CG, Thomas SM, Chervin
RD.Clinical Practice Guideline for the Treatment of Obstructive Sleep
Apnea and Snoring with Oral Appliance Therapy: An Update for 2015.J
Clin Sleep Med 2015;11(7):773-827.
41. Richardson GS, Zammit G, Wang-Weigand S, Zhang J.Safety and
subjective sleep effects of ramelteon administration in adults and older
adults with chronic primary insomnia: a 1-year, open-label study.J Clin
Psychiatry 2009;70(4):467-76.
42. Rojas-Fernandez CH, Chen Y.Use of ultra-low-dose (≤6 mg) doxepin for
treatment of insomnia in older people.Can Pharm J (Ott) 2014;147(5):281-
9.
43. Roth T, Wright KP Jr, Walsh J.Effect of tiagabine on sleep in elderly
subjects with primary insomnia: a randomized, double-blind, placebo-
controlled study.Sleep 2006;29(3):335-41.
44. Russell T, Duntley S.Sleep disordered breathing in the elderly.Am J Med
2011;124(12):1123-6.
45. Ruwe F, IJzerman-Boon P, Roth T, Zammit G, Ivgy-May N.A phase 2
randomized dose-finding study with esmirtazapine in patients with primary
insomnia.J Clin Psychopharmacol 2016;36(5):457-64.
46. Savarese M, Carnicelli M, Cardinali V, Mogavero MP, Federico F.Subjective
hypnotic efficacy of trazodone and mirtazapine in patients with chronic
insomnia: a retrospective, comparative study.Arch Ital Biol 2015;153(2-
3):231-8.
47. Seyffert M, Lagisetty P, Landgraf J, Chopra V, Pfeiffer PN, Conte ML, Rogers
MA.Internet-delivered cognitive behavioral therapy to treat insomnia: a
systematic review and meta-analysis.PLoS One 2016;11(2):e0149139.
48. Sharma S, Trivedi JK. Guidelines for the treatment of sleep disorders.
(Eds): Shiv Gautam & Ajit Avasthi. Published by Indian Psychiatric Society,
2006; Volume II, 232-264.
49. Thompson W, Quay TA, Rojas-Fernandez C, Farrell B, Bjerre LM.Atypical
antipsychotics for insomnia: a systematic review.Sleep Med 2016;22:13-7.
S396
50. Trauer JM, Qian MY, Doyle JS, Rajaratnam SM, Cunnington D.Cognitive
behavioral therapy for chronic insomnia: a systematic review and meta-
analysis.Ann Intern Med 2015;163(3):191-204.
51. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al;
International Restless Legs Syndrome Study Group.Validation of the
International Restless Legs Syndrome Study Group rating scale for
restless legs syndrome.Sleep Med 2003;4(2):121-32.
52. Yoon IY, Kripke DF, Elliott JA, Youngstedt SD, Rex KM, Hauger RL.Age-
related changes of circadian rhythms and sleep-wake cycles.J Am Geriatr
Soc 2003;51(8):1085-91.
53. Zhu Y, Long H, Jian F, Lin J, Zhu J, Gao M, Lai W.The effectiveness of oral
appliances for obstructive sleep apnea syndrome: A meta-analysis.J Dent
2015;43(12):1394-402.
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Clinical Practice Guidelines for Management of Delirium in Elderly
Sandeep Grover, Ajit Avasthi
Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, Correspondence:
drsandeepg2002@yahoo.com
INTRODUCTION
Delirium is an acute, transient, usually reversible
neuropsychiatric syndrome, seen in medical-surgical set-ups.
It is considered to be a serious problem in acute care settings.
Although delirium is encountered in all age groups, elderly
are considered to be a high-risk group for development of
delirium. It basically reflects decompensation of cerebral
functions, as a result of one or more pathophysiological
processes. Unfortunately, on many instances delirium is not
detected or the detection is delayed. Delirium is known to
be associated with varied negative outcomes like prolonged
hospital stay, need for institutional care, poor functionality
and high treatment costs. It has also been shown to be
associated with high short-term and long-term mortality.
Besides these, delirium has been shown to be associated
with significant distress to the patient and the family. Due
to all these negative consequences, it is very important
to prevent the development of delirium in medically ill
patients. It is also important to detect this entity at the
earliest and manage the same to reduce the associated
morbidity, mortality and distress among patients and their
caregivers. Earlier it was thought that delirium is not
associated with any long-term consequences, but now it is
increasingly being recognised that in the long run, delirium
is associated with cognitive decline and development of
dementia.
Indian Psychiatric Society had published clinical practice
guidelines (CPGs) for management of various psychiatric
disorders amongst elderly for the first time in the year 2007.
In the earlier version, management of delirium was included
under the CPGs for management of Psychosis amongst
elderly. This time it is felt that management of delirium
involves a broader range of evaluations and interventions
and hence, an effort is made to have separate CPGs for
management of delirium. The new guidelines are an attempt
to provide updated information on the subject and use the
newer information in formulating the guidelines. Although
these guidelines are published as part of CPGs for Geriatric
Psychiatry, these guidelines can also be applied to patients
of other age groups with delirium.
For these guidelines, Internet searches were carried out
by using search engines of PUBMED, Embase and Google
Scholar to find out the available evidence based literature
© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
both for non-pharmacological and pharmacological
management. Available treatment guidelines on the topic by
different organizations were also reviewed for formulation
of the guidelines.
Epidemiology of delirium
Epidemiology of delirium has been evaluated across
different treatment settings across the world and the
incidence and prevalence is influenced by the treatment
setting (Intensive care units, medical/surgical ward, post-
operative patients, consultation-liaison psychiatry services),
population assessed (elderly, pediatrics, adult, mixed
age group) and method used for estimation (screening
instrument, diagnostic instrument) of delirium. In general,
data suggest an incidence rate of 3 to 42% in hospitalized
patients and prevalence to vary from 5 to 44% amongst
the hospitalized patients. Data also suggests that the
incidence and prevalence of delirium is much higher among
patients admitted to various intensive care units (ICUs) with
prevalence reported to be as high as 82% with higher rates
amongst those requiring mechanical ventilation. Studies
evaluating patients in the emergency department, suggest
that about 40% of patients have delirium. Studies from India,
which have evaluated the incidence of delirium in various
intensive care units, have reported prevalence rates to vary
from 26.2% to 68.2% and the incidence rates to vary from
9.27 % to 59.6%. Studies, which have evaluated the course
of delirium in ICU settings, suggest that the delirium usually
starts after 2 (SD-1.7) days of admission to the ICU and lasts
for 4.2 (SD-1.7) days.
Nosology
With each revision of the Diagnostic and Statistical Manual
(DSM), American Psychiatric Association has made certain
modifications in the diagnostic criteria of delirium. The DSM-
III version gave importance to ‘clouding of consciousness
with a reduced capacity to shift, focus and sustain attention’
as the core feature. Subsequent revision, i.e., DSM-III-R,
shifted the emphasis from ‘clouding of consciousness’ to
‘reduced attentiveness’ and ‘disorganized thinking’. Each
of these was defined as a major criterion and the term
‘clouding of consciousness’ was dropped. The DSM-IV took
a reverse turn and again laid emphasis on ‘disturbance in
consciousness and inattention’ as one of the major criteria.
The most recent version, i.e., DSM-5 again lays importance
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Grover and Avasthi: Management of Delirium in Elderly
on disturbance in attention (i.e., reduced ability to direct,
focus, sustain, and shift attention) and awareness (reduced
orientation to the environment) and do not consider
clouding of consciousness in its clinical criteria of delirium
(Table-1). Some of the researchers have questioned this
change in emphasis and have shown that the interpretation
of the criteria can influence the epidemiology of delirium.
The World Health Organization’s International
Classification of Diseases (10th revision) defines delirium by
disturbance in cognition manifested by both ‘impairment
of immediate recall and recent memory’ and ‘disorientation
to time, place and person.’ Additionally, criteria in ICD-10
include ‘disturbance in sleep wake cycle’, ‘psychomotor
disturbances’, and ‘emotional disturbances’. ICD-10 also
specifies the upper limit of 6 months for delirium. Some of
the studies which have evaluated the concordance between
DSM-IV and ICD-10 criteria suggest that DSM-IV is more
sensitive than ICD-10 for the diagnosis of delirium.
Clinical features of delirium
The clinical features of delirium include a constellation
of symptoms encompassing physical, biological and
psychological disturbances. It is characterised by an acute
onset of symptoms, with a fluctuating course. The symptoms
of delirium are broadly divided into cognitive, non-
cognitive and motoric symptoms. The cognitive symptoms
include disturbances in attention, memory, orientation,
comprehension, vigilance, visuo-spatial abilities and
executive functioning. Of the various cognitive functions,
inattention is considered to be the most consistent feature
and accordingly is included as a diagnostic criterion.
Disturbance in attention involves all aspects, i.e., ability
to mobilize, shift and sustain attention. Impairments in
memory can involve both short- and long-term memory with
significant impairment in recent memory. Disorientation to
time, place and person is also very common. Visuo-spatial
disturbances and executive dysfunction when present
impair the functionality of the patients. The non-cognitive
Table-1: DSM-5 criteria for Delirium
A. A disturbance in attention (i.e., reduced ability to direct, focus,
sustain, and shift attention) and awareness (reduced orientation to the
environment).
B. The disturbance develops over a short period of time (usually hours to
a few days), represents a change from baseline attention and awareness,
and tends to fluctuate in severity during the course of a day.
C. An additional disturbance in cognition (e.g. memory deficit,
disorientation, language, visuospatial ability, or perception).
D. The disturbances in Criteria A and C are not better explained by a
pre-existing, established or evolving neurocognitive disorder and do
not occur in the context of a severely reduced level of arousal, such as
coma.
E. There is evidence from the history, physical examination or laboratory
findings that the disturbance is a direct physiological consequence of
another medical condition, substance intoxication or withdrawal, or
exposure to a toxin, or is due to multiple etiologies.
S330
symptoms of delirium include disturbances in the sleep
wake cycle, speech and language disturbances, affective
lability, perceptual abnormalities (hallucinations, illusions
etc.) and delusions. Sleep-wake cycle disruptions can
range from napping and nocturnal disruptions to asevere
disintegration of the normal circadian rhythm. The motoric
symptoms of delirium include an increase or decrease in the
psychomotor activity. Based on the psychomotor activity,
delirium is subtyped as hyperactive, hypoactive and mixed.
The most common subtype of delirium varies from one
treatment setting to the other. Studies based on referrals
to the consultation-liaison psychiatry (CLP) teams suggest
that hyperactive delirium is the most common subtype of
delirium. On the other hand, studies involving ICU patients
or studies that have reported data of inpatients screened
for delirium suggest that hypoactive delirium is the most
common subtype of delirium. Recognising the subtypes of
delirium can have an important prognostic implication, as
studies have shown that hypoactive subtype is associated
with higher mortality rates.
Risk factors/etiology for delirium
Delirium is often multi-factorial in origin. Data on risk factors
is mainly available from the hospital-based studies. Certain
risk factors have been found to be consistent across various
treatment settings, whereas other risk factors are specific
to a particular treatment setting. The commonly identified
risk factors are shown in Table-2. Among these factors,
certain factors are considered to predispose or increase
vulnerability to develop delirium while certain factors have
been shown to be associated with development of delirium.
Keeping this in mind, some authors categorise the factors
associated with delirium as risk factors/ predisposing
factors and etiological/precipitating factors. Accordingly,
predisposing factors are defined, as factors, which depict
the vulnerability of an individual to develop delirium and
these, are usually present prior to admission to the hospital
and are considered to have a larger contribution than the
precipitating factors for the onset of delirium. In contrast
to these, precipitating factors are noxious insults or hospital-
related factors, which contribute to the development of
delirium and are often detected at the time of detection of
delirium. However, this categorisation is arbitrary, as there
is some overlap in these factors.
Of all the risk factors, higher age, presence of cognitive
impairment, severe concomitant medical illnesses, and
receiving medications are considered as ‘robust risk factors’.
The commonly associated risk factors for delirium among
elderly in acute hospital medical units include presence of
dementia, older age (> 70 years), higher severity of medical
illness, infection, use of ‘high-risk’ medications, reduction
in activities of daily living, being immobile, sensory
deprivation/impairment, presence of insitu urinary catheter,
raised urea levels, electrolyte imbalance, malnutrition and
longer duration of hospital stay.
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Table-2: Risk factors for delirium
Socio-demographic variables: age > 70 years/ advanced age, male
gender, institutionalization,
Baseline Mental Status: cognitive impairment/ dementia, depression,
social isolation
Past History: previous history of delirium
Sensory impairment: vision and/or hearing impairment
Medical Illnesses: severe medical illness, high APACHE II score, fracture
at admission to the hospital,brain disorders like Parkinson’s disease,
tumors, Iinfections
Physical Status: fever, hypotension, poor functionality/immobility, limited
pre-morbid activity levels
Metabolic disturbances: electrolyte imbalance, anaemia, acid base
imbalance, hypoglycaemia
Medications
Sedative-hypnotics: benzodiazepines; especially long acting agents,
barbiturates, Antihistamines (e.g., diphenhydramine)
Narcotics: Meperidine
Drugs with anticholinergic effects: Oxybutynin, Tolterodine,
Antihistamines, Antipsychotics (e.g., low potency neuroleptics such as
chlorpromazine), Promotility agents, Tricyclic antidepressants (especially
amitriptyline, imipramine and doxepin), Cumulative effect of multiple
medications with anticholinergic effects
Histamine-2 Blocking agents: Cimetidine
Anticonvulsants: Phenytoin, Phenobarbitone
Antiparkinsonian medications: Dopamine agonists, Levodopa-carbidopa,
Amantadine, Anticholinergics, Benztropine
Use of more than 3 medications
Laboratory Findings: High urea/creatinine ratio, Hypo/Hypernatremia,
Hypo/hyperkalaemia, Hypoxia, hepatic failure
Surgery and Anaesthesia: Unplanned (i.e., emergency) surgery,
Immobility after surgery, preoperative use of narcotic analgesics, type of
surgery (hip replacement surgery, neurosurgery), emergency surgery, longer
duration of surgery, type of anaesthetic, postoperative pain, intraoperative
blood loss
Pain: poor pain management
Nutrition: Malnutrition, dehydration,hypoalbuminemia
Treatment related factors: use of physical restraints, indwelling
Cather, more number of procedures including investigations during early
hospitalization (X-rays, blood tests etc.)
Sleep: sleep deprivation/insomnia
Treatment setting: Intensive care units, longer duration of hospital stay
Others: Alcohol abuse, Urgent hospitalization, frequent hospitalizations
Differential Diagnosis
The differential diagnosis of delirium includes dementia,
depression and psychosis/ schizophrenia. Dementia is a risk
factor for delirium and is also a differential diagnosis for
delirium. Careful history taking can help in distinguishing the
two disorders. Delirium is characterised by an acute onset
of illness; in contrast, dementia usually has an insidious
onset. The cognitive symptoms in dementia manifest in
the absence of an altered level of consciousness, whereas
delirium is often characterized by an altered level of
consciousness. Further, dementia usually follows a downhill
course, whereas delirium is often reversible. However, it is
important to remember that many patients may present
with delirium superimposed on dementia and the symptom
profile of patients with delirium with or without dementia
do not differ much. Depression is also considered as a risk
factor for delirium. History taking should focus on eliciting
the history of persistent sadness of mood and morning
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Grover and Avasthi: Management of Delirium in Elderly
worsening of symptoms. In contrast to this, delirium is often
characterized by lability of mood and evening worsening
of symptoms, which is also known as sun-downing effect.
Primary psychiatric disorders are often characterized by
presence of auditory hallucinations, whereas delirium is
predominantly characterized by presence of visual and
tactile hallucinations. Cognitive disturbances are present in
patients with primary psychotic disorders though these are
not as prominent as seen in patients with delirium.
Assessment Scales for Delirium
As delirium is commonly seen in medical-surgical settings,
detection of the same requires a high index of suspicion
on the part of the treating physician/surgeon. Various
instruments have been designed to screen, diagnose
and rate the severity of delirium. Separate screening and
diagnostic instruments have been designed to assess
delirium in different treatment settings,(for example,
medical-surgical wards and ICUs). Additionally, instruments
have also been designed for different age groups as well as
to rate the motoric symptoms in delirium(Table-3).
Screening instruments are recommended for non-mental
health professionals. Amongst the various screening and
diagnostic instruments, Confusion Assessment Method
(CAM) is commonly used for both screening and diagnosing
delirium by non-mental health professionals. It can be
administered in a short span of time (usually 5 minutes)
and has been shown to have good psychometric properties.
Confusion Assessment Method for Intensive Care Unit (CAM-
ICU) has been specifically designed to assess delirium in the
ICU setting. It can be used in patients who cannot speak
(for example those on mechanical ventilation). CAM-ICU
can be used in patients who are arousable to verbal stimuli
and can be completed within 1 to 2 minutes by a trained
health care professional. CAM-ICU has been shown to have
a higher sensitivity (95-100%) and specificity (93-98%), when
compared with the diagnosis of delirium made by a mental
health professional using DSM-IV criteria. CAM-ICU has also
been shown to have high interrater reliability (0.79 to 0.95).
For rating of severity of delirium, Delirium Rating Scale-
Revised-98 (DRS-R-98) has been the most commonly used
scale in recent times. Compared to the previous version,
the revised version has a provision for evaluating cognitive
symptoms, non-cognitive symptoms, and motoric symptoms
and also has diagnostic items. DRS-R-98 has 16 items, out
of which 3 items are of diagnostic importance. Patient’s
behaviour is rated on the basis of information available from
all the sources including the mental status examination. Each
severity item is rated from 0 (no impairment) to 3 (severe
impairment), with a severity score > 15 and a total score
of > 18 is indicative of delirium. Higher scores on the scale
indicate a much more severe delirium. The DRS-R-98 total
score is able to distinguish patients with delirium from those
with other mental disorders like dementia, schizophrenia,
and depression during blind rating, with a sensitivity ranging
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Grover and Avasthi: Management of Delirium in Elderly

from 91% to 100% depending on the cut-off score chosen. It symptoms and subtyping delirium. In case patient has
is also the one of the commonest scales used for evaluating alcohol withdrawal delirium then appropriate scales like
the symptom profile or the phenomenology of delirium in revised Clinical Institute Withdrawal Assessment for Alcohol
various studies. The scale has also been used for monitoring Scale (CIWA-Ar) can be used to quantify the severity of
the severity of delirium over a period of time and has been alcohol withdrawal syndrome at the baseline and for
used as an outcome measure in different medication trials. monitoring the symptoms over time.
However, it is important to remember that DRS-R-98 has not
been validated in the ICU setting. Once a patient is diagnosed with delirium, management
should involve identification of possible causes, correction/
Mini Mental Status Examination (MMSE) is also used for removal of the etiological factors, and management of
evaluating the cognitive impairment in patients with symptoms of delirium by using both pharmacological and
delirium. However, it is important to remember that MMSE non-pharmacological treatment.In addition, the clinician
can evaluate only the cognitive dysfunction. should play a role in prevention of any complications and
provide adequate information to the family (Table-4).
Management of Delirium
Delirium is a psychiatric emergency, management of which General Principles of Assessment of underlying cause(s),
requires proper detection, identification of the cause and contributory and maintaining factors for delirium
treatment of symptoms (Figure-1 & 2). First and foremost, Once the diagnosis of delirium is established with certainty
it involves making a correct diagnosis. Diagnosis should be then all efforts must be made to identify the underlying
based on any standard nosological system as appropriate cause for delirium (Table-5). Elderly patients are often
rating scales must be used to rate the severity of the not able to provide proper history and in such a scenario
efforts must be made to collect the information from all
the collateral resources. A thorough review must be
Table-3: Commonly Recommended Scales for
done for medications received including the prescription
Assessment of Delirium
and over the counter medications. Due attention must
Purpose Instrument
be paid to addition of any new drug or an increase in
Screening Delirium Observation Screening Scale/Delirium
dosage of medication (s). If there is a close link between
instruments for Observation Scale
delirium Global Attentiveness Rating onset of delirium and change in the dosage or starting
Intensive care delirium screening checklist of a medication then it can be considered as a possible
NEECHAM Confusion Scale offending agent. Detailed physical examination needs to be
Nursing Delirium Screening Scale done to evaluate all the possible causes of delirium. In terms
Paediatric Anesthesia Emergence Delirium scale
of investigations, neuroimaging is not indicated routinely
Clinical Assessment of Confusion - A and B
CAM and must be considered in persons having suspicion of
Diagnostic CAM-ICU intracranial lesions, i.e., patients having focal neurological
instruments for Confusion Assessment Method signs, history of head injury/trauma just prior to onset of
delirium Delirium Rating Scale-revised version symptoms, presence of papilloedema indicating raised
Diagnostic instruments Delirium Symptom Interview
intracranial pressure. Similarly electroencephalogram
Memorial Delirium Assessment Scale
Paediatrics CAM-ICU should not be done routinely.
Saskatoon Delirium Checklist
Instruments to Confusion Assessment Method for Intensive Care Unit Management for the underlying cause(s) of delirium
assess severity of assessment tool Once a cause is identified it should be treated with adequate
delirium Confusion Assessment Method
measures. It is important to remember that on many
Confusional State Evaluation Scale
Delirium Assessment Scale occasions, more than one factor lead to delirium, i.e., there
Delirium Index may be just one offending agent but multiple contributory
Delirium Rating Scale factors. In case the delirium is attributed to a medication,
Delirium Rating Scale-Revised-98
Delirium Severity Scale Table-4: General Principles of Management of Delirium
Delirium-O-Meter
Identify the cause(s), contributory and maintaining factors for delirium
Memorial Delirium Assessment Scale
• Manage the cause(s) of delirium: discontinue or reduce the dose of
Instruments for Delirium Motor Checklist, Delirium Motor Symptom
causative agent, correct electrolyte imbalance, treat infection, use specific
assessment of Scale
antidotes if delirium is related to poisoning or toxic conditions
motoric symptoms Memorial Delirium Assessment Scale
• Communication with the primary treating team
Motoric items of Delirium Rating Scale, DRS-R-98
• Educate the family about the condition: nature, symptoms, their role in
Richmond Agitation and Sedation Scale
management
Instruments used Mini Mental Status Examination (MMSE)
•  Monitor the patients clinical status
for assessment of Hindi Mental State Examination (HMSE)
• Non-pharmacological measures
cognitive functions Montreal Cognitive Assessment (MoCA)
• Pharmacological agents
only Abbreviated Mental Test (AMT)
• Prevent development of secondary complications; falls, bed sores

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Figure-1: Assessment of patients with Delirium
the offending agent must be removed in consultation with
the primary treating team. Additionally all non-required
medications need to be stopped in liaison with the primary
treating team (Table-6).
At times delirium may not be attributed to one specific
medication, but it may be due to cumulative anticholinergic
properties of various medications received. This can be
done by using available charts like Anticholinergic Burden
Classification (ABC), Anticholinergic Drug Scale (ADS),
Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive
Burden Scale (ACB), Clinician-rated Anticholinergic Score,
Anticholinergic Activity Scale (AAS) and Anticholinergic
Loading Scale (ACL). Among these instruments, ABC is
the most commonly used scale. The ABC provides a list of
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Grover and Avasthi: Management of Delirium in Elderly
Figure-2: Management of Delirium
medications along with their anticholinergic propensities.
The drugs are rated from 1 to 3 depending on the
anticholinergic properties. This can help in understanding
the anticholinergic load and identifying the agents, which
need to be stopped. If delirium is related to an infection,
appropriate measures must be taken treat the infection.
Appropriate antidote must be used in case delirium is
related to a poisoning or intoxication. If delirium is related
to alcohol withdrawal, then benzodiazepines must be
considered. Additionally, measures like use of high doses
of thiamine must be carried out. Many elderly patients
are prone to have nutritional deficiencies and if these are
suspected then use of multivitamins may be considered.
Communication with the primary treating team
As delirium is most often encountered in the consultation-
liaison psychiatry set-up, communication with the
primary treating team forms an important aspect of the
management. Often the physicians and surgeons equate
delirium with other psychiatric disorder, which do not have
underlying physical causes and request to shift the patient
to the psychiatric unit. In such situations, it is important
to explain to the primary team members that although the
patient is having symptoms similar to some of the other
psychiatric disorders like psychosis, but delirium is a result
of an underlying medical-surgical aetiology and is reversible.
Emphasis must be laid upon the fact that correction of
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Grover and Avasthi: Management of Delirium in Elderly
Figure-3: Management of Alcohol Withdrawal Delirium
underlying cause can reverse the process. Besides this, the
primary treating team must be explained about the role of
non-pharmacological and supportive measures and the use
of psychotropics to manage delirium.
Educate the family about delirium
Family members often experience significant distress on
seeing the clinical manifestation of delirium. They are
also often ignorant about their role in management of
delirium. Hence, it is of utmost importance to address the
family members as they can be an important integral part
of the management. They should be provided adequate
information about the nature of the syndrome, symptoms
and their role in management (Table-7).
Monitoring of the patient
All patients with delirium require close monitoring till
the symptoms subside. Monitoring over a period of time
must be done to avoid emergence of newer factors, which
can worsen the delirium and can lead to continuation
of symptoms of delirium. Other important aspects of
monitoring include ensuring safety of the patient, ensuring
adequate sleep, avoiding development of complications like
bed sores and falls (Table-8). In general physical restraints
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Table-5: General Principles for Assessment of cause of
delirium
Baseline evaluation of patient
• Confirm the diagnosis of delirium by using standard diagnostic criteria
• Rate the severity of delirium, subtype the delirium
• Evaluate the risk of harm to self or others
• Evaluate the onset and the course of symptoms
• Evaluate the underlying medical illnesses- both acute and chronic
• Look for information about recent procedures- surgery, drainage etc
• Alcohol and other substance use pattern- last intake, relationship with
onset of symptoms of delirium
• Psychiatric comorbidity
• Previous level cognitive functioning
• Past history of delirium and response to treatment
• Level of functioning (i.e., basic and instrumental activities of daily living)
• Psychosocial history- social isolation
• Look for symptoms which can indicate the possible cause (fever
suggestive of infection)
• Sensory impairment/deprivation
• Physical restraints, urinary Cather etc
• Sleeping pattern- duration of sleep, diurnal pattern of sleep
• Functioning of bladder and bowel – constipation, impaction of faecal
material
• Dietary and fluid intake
Review of Medications
• Review the medication history- total number of drugs, type of drugs, over
the counter use of drugs, use of drugs from alternative medicine, any
recent change (addition or deletion) of drugs and their association with
emergence of symptoms of delirium
• Review the anaesthesia records in post-operative patients
Baseline Physical Examination
• Thorough physical examination from head to toe
• Neurological examination- evaluate the level of consciousness
• Review the vital signs in postoperative patients – look for hypertension,
hypotension
• Hydration status and nutritional status
• Signs and symptoms of local or systemic infection- fever, crepitations in
the chest etc
• Look for signs and symptoms of alcohol withdrawal/intoxication or those
related to other substances
Baseline evaluation of the Environment
• Sensory deprivation or overload (example, too much noise, beeps etc)
• Changes around: frequent change of rooms, frequent change of staff,
• Involvement of the family- isolation from family
• Familiarity with the surroundings
• Presence or absence of calendars, clock etc)
Basic Investigations
• Serum electrolytes- sodium, potassium, calcium, magnesium
• Haemogram
• Renal function test- urea, creatinine
• Liver function test- Alkaline phosphatase, alanine aminotransferase
(ALT), Aspartate aminotransferase (AST)
• Blood glucose levels
• Thyroid function test
• Arterial blood gas (ABG) analysis
• Urine analysis- routine, culture
• X-ray Chest
• Electrocardiogram (ECG)
• If indicated than consider urine drug screen, blood cultures, serum level
of medications, computerized tomography (CT) or magnetic resonance
imaging (MRI)
• If indicated consider Electroencephalogram (EEG): can help in
distinguishing delirium from dementia, when delirium sis thought to be
associated with status epilepticus, partial complex seizures, can help to
distinguish hypoactive delirium from depression
• Lumber puncture if meningitis is suspected
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Table-6: Management of Underlying Cause(s)
•  Remove the offending agent (s) associated with development of delirium
•  Use scales like Anticholinergic Burden Classification (ABC) to evaluate
the anticholinergic propensity of all the prescribed drugs which patient is
receiving and minimize the anticholinergic load
•  Remove all the unnecessary medications
•  Treat underlying infections with appropriate antibiotics
•  Poisoning and Intoxication: use appropriate antidote
•  Delirium related to Alcohol Withdrawal: Benzodiazepines, Thiamine
Table-7: Educate the family members about delirium
•  Explain the family members that the symptoms are due to underlying
organic cause
•  Explain that the symptoms are transitory and will subside in short
duration
•  Explain family members about their role in management of delirium
Table-8: Monitoring of patients with delirium
•  Rate the severity of symptoms over time
•  Serial assessment of cognitive functions
•  Review sleep chart
•  Ensure safety of the patients
•  Close observation and monitor the vital signs, temperature, oxygenation,
hydration, electrolytes, glucose level, nutrition, input/output
•  Regularly evaluate the patients and take measure to avoid development
of pressure sores
•  Reduce immobility – encourage performance of self-care activities on
their own, allow free movements
•  Remove the catheter as soon as possible
•  Monitor bladder and bowel habit and maintain normal elimination
patterns
•  Monitor the prescription with special focus on evaluation of potential
adverse drug-drug interactions and drug-disease interactions
must be avoided as far as possible. Physical restraints
may be considered when there is a serious risk for bodily
harm to self or other, other measures to control (i.e.,
pharmacotherapy have failed) and the potential benefits
outweigh the risks of using restraints. When required, least
restrictive physical restraints be used and for the shortest
possible duration and must be removed when the potential
harm threatening behaviours have subsided or if the patient
develops physical complications due to the use of restraints.
Non-Pharmacological Management
Non-Pharmacological treatment involves providing
unambiguous, supportive environment to improve the
orientation and maintain the competence of the patients.
The components of this can be divided into providing support
and orientation, providing unambiguous environment,
measures at maintaining competence and providing other
supportive measures (Table-9). Many studies have evaluated
the various components of the non-pharmacological
interventions in delirium. However, there are limited
numbers of randomised control trials (RCTs), which have
evaluated non-pharmacological interventions. Findings
from various RCTs suggest that systematic detection and
multidisciplinary care do not appear to be superior than
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Grover and Avasthi: Management of Delirium in Elderly
Table-9: Non-pharmacological measures for delirium
Providing support and orientation
• Communication: use simple language, communicate in clear, simple,
firm, slow-paced language and if require repeat the instruction
• Avoid abstract ideas/language
• Avoid discussion which cannot be appreciated by the patient
• Discuss topics which the person with delirium is interested in talking, is
familiar with such as his hobbies and profession
• Reorientation: reorient the patient (repeated reminders for the day, time
and location, and identity of key individuals including treating team
members)
• Address the patient face-to-face, make proper eye contact, and give clear
instructions when talking to patients
• Convey an attitude of warmth, calmness and kind firmness
• Understand the persons emotional state and encourage them to speak
• Do not try to provide too much of information at one go and when patient
is not interested
• Clear markers/signs for patient’s location
• Provision for calendar, clock, chart with the day’s schedule in the
patients room
• Avoid multitasking: provide one stimulus/task at a given time
• Bring familiar belonging from the home: personal/familiar objects
(Photos, favorite blanket), night clothes, things kept at bedside in the
home to enhance orientation and security
• If interested, patient may be encouraged to carry out cognitively
stimulating activities: many times a day (puzzle books, Sudoku,
magazines, or video games etc.)
• Minimize change of staff
• Use a television/radio/smartphones/listening to music etc. for relaxation
can be allowed if the person wants the same, as these can help the patient
maintain contact with the outside world; light music can prevent under
stimulation and also provide a buffer against noise extremes
• Physical restraints to be kept away, if possible; when used should be for
shortest possible duration and be removed in timely manner
• Encourage feelings of security and orientation by involving family
members/caregivers
• Explain about each procedure or the act being done as part of treatment
or general care (for example changing the bed sheet), to reduce the
chances of misinterpretation
• Position your hands in the field of the vision and avoid rapid movements
or gestures, which could be misinterpreted as signs to harm
• In case patient gets agitated, look for the triggers and use behavioural
strategies (change in the environment, distraction) to reduce agitation
• Do not contradict the delusional beliefs- this can enhance the agitation
and encourage disorientation
• Do not confront and disagree with the patient, even if the patient
verbalizes inappropriate or inaccurate things
• Avoid having more than one patient with delirium in the same room,
especially persons with agitated hyperactive delirium, as agitation of one
patient reinforces/induces the agitation in the second patient
Providing an unambiguous environment
• Remove harmful and unfamiliar objects from the vicinity
• Avoid both sensory deprivation (provide glasses and hearing aids, if
patient was using the same) and sensory overload (noise)
• Do away with unnecessary objects in the care area, maintain adequate
space between beds
• If the provision exist or it is possible that, provide single room: will
help in providing rest and lead to avoidance of extremes of sensory
experience; this can also eliminate the disturbance caused by staff/family
caregivers of other patients in the same room
• Frequent change of location of patient’s bed should not be done
• Do not use medical jargon in front of the patient as this can enhance the
feelings of paranoia
• Adequate lighting: appropriate lighting to the time of day and minimal
lighting at night may reduce disorientation (40–60 W night light reduces
misperceptions)
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• Quiet environment, reduce noise (keep phones in the silent/vibrator
mode, use vibrating beepers, reduce the noise from staff, equipment,
visitors to the minimum with a aim of <45 decibels during the daytime
and <20 decibels at night)
• Room temperature to be maintained between 21°C and 23.8°C
• Encourage family members to stay with the patient- can help in
reorientation, provide a sense of safety, help in effective communication
• Educate the family about how to communicate
Maintaining competence
• Recognise and correct sensory impairments: make sure that patients have
their glasses, hearing aids and dentures
• Check whether patient understands your language or an interpreter is
required; if so use an interpreter
• Early mobilization: Ambulate at the earliest, if this is not possible than
encourage whole range of movements for at least 15 minutes three times a day
• Encourage independence in self-care activities
• Encourage participation in treatment (for example, encourage the patient
to give feedback about their pain)
• Ensure good uninterrupted sleep: schedule treatment/interventions/
Intravenous fluids in such a way that patient can have maximum periods
of uninterrupted sleep (use a sleep protocol to promote quiet hours)
• Address the issues related to nutrition
• Do away with urinary catheter, central line, Intravenous fluid line etc at
the earliest
• Adequate skin care and avoid development of bed sores
• Proper measures to be taken to prevent falls
Other supportive measures
• Maintain adequate oxygen saturation, correct electrolyte imbalance
• Adequate pain management: use non-pharmacological measures, local
measures, in case of severe pain use appropriate analgesics (preferable
non-narcotic agents) round the clock
• Unnecessary medications to be discontinued
• Treat infection: antibiotics
• Ensure regular bowel/bladder habits: avoid constipation
• Prevention, detection, management of major postoperative complications
Educate the Staff
• How to recognise and monitor the symptoms of delirium
• How to provide reorientation cues
Table-10: Pharmacological management of Delirium
Antipsychotics: haloperidol, Droperidol, chlorpromazine, loxapine,
risperidone, quetiapine, olanzapine, aripiprazole, zuclopenthixol,
ziprasidone, perospirone etc
Benzodiazepines: Lorazepam
Cholinesterase inhibitors: Donepezil, Physostigmine, Rivastigmine
Highly selective α-2 receptor agonist: dexmedetomidine
Melatonin based medications: Remelteon
Others: Ketamine
Table-11: General Principles of use of antipsychotics in
Delirium
• Weigh the benefits and risks of using antipsychotics
• Antipsychotics must be started in liaison with the family/caregivers and
members of the primary treating team
• Before starting antipsychotics- baseline ECG must be done to evaluate
the QTc interval
• Clearly document the indications for starting antipsychotics
• Use lowest effective dose
• Start with lower doses and gradually titrate upwards
• Monitor the symptoms of delirium
• Monitor for side effects: over-sedation, extrapyramidal side effects
• In general, antipsychotics are not recommended for management of
patients with hypoactive delirium
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usual care provided to elderly patients admitted to medical
services. However these studies have been criticised for
the limitations in the form of a contamination effect, i.e.,
patients in both the intervention arms were managed in the
same units by the same staff.
Pharmacological treatment for delirium
A wide range of pharmacological agents has been evaluated
for the management of delirium (Table-10). Factors, which
influence the medication selection, include the treatment
setting (medical-surgical ward/ICU/ Palliative care), treating
agency (Intensive care interventionist versus CL Psychiatrist)
and the clinical demand (hyperactive/hypoactive delirium).
Use of pharmacological agents must be weighed against
the possible side effects. Pharmacological management
is not indicated in all the patients. It is suggested that
pharmacotherapy be considered when non-pharmacological
measures have failed to manage the patient in ease or
there are specific indications for its use. The most common
indication for pharmacological management includes severe
agitation or severe anxiety causing significant distress to
the patient or placing the patient at risk to harm themselves
or others. Other indications for pharmacotherapy include
a lack of cooperation in treatment to the extent that it is
difficult or impossible to carry out essential investigations
or treatment procedures. Further, despite the best attempts
at carrying out non-pharmacological treatment, symptoms
of delirium are persisting.
Antipsychotics: In general, antipsychotics are considered as
the medication of choice in the management of delirium.
Studies have evaluated various antipsychotics in the
management of delirium. However, there are a very few
double blinded randomised placebo controlled trials which
have evaluated the efficacy of antipsychotics in patients with
delirium. Available trials are also limited by a small sample
size and heterogeneity in the treatment setting, in which
the studies have been carried out. Despite these limitations
most of the experts agree on the use of antipsychotics for a
short duration in the management of delirium.
Antipsychotics have been reported to reduce the agitation,
anxiety, associated psychotic symptoms, have a sedative
effect and have also been shown to improve the cognitive
symptoms of delirium. Decision to start antipsychotics must
be taken in liaison with the family/caregivers and members
of the primary treating team.
The important thing to remember is that, the mean doses
required to control the symptoms of delirium are significantly
less than the dose usually used in the management of other
psychiatric disorders. Hence, whenever antipsychotics are
used, these must be started in lower doses and slowly
titrated upwards (Table-11 and 12).
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In terms of selection of an antipsychotic medication,
haloperidol is the most preferred agent. It is one
of the oldest molecules used in the management
of delirium. In fact, all the newer antipsychotics, which
have been evaluated in the management of delirium,
have been compared against haloperidol. Haloperidol
has certain advantages over other antipsychotics. It is
available in different formulations (oral, intramuscular
and intravenous routes) and reported to be associated
with a lower risk of sedation and hypotension. It is
usually started in low doses, i.e., in the dose range of
0.25–0.50 mg 4 hourly for elderly. Doses are titrated as
per the need. As haloperidol is thought to be associated
with a high incidence of cardiac conduction problems
such as prolongation of the QT interval and arrhythmias,
which can lead to torsades de pointes and ventricular
fibrillation, electrocardiogram (ECG) must be closely
monitored. In terms of efficacy, most of the recent
trials which have compared haloperidol with various
other antipsychotics suggest that it is as efficacious/
effective as other antipsychotics. However, occasional
studies, which have evaluated haloperidol against
placebo in palliative care settings, have reported it to be
inferior to placebo in reducing symptoms of delirium.
A recent review of data on haloperidol suggests that it
is associated with reduction in severity of symptoms
in delirium. Regarding the side effects of haloperidol,
the authors concluded that although side effects do not
limit its use in delirium, but at the same time cautioned,
that only a few studies have systematically assessed the
adverse events.
In the last decade or so, some data has been generated
for the efficacy/effectiveness of other antipsychotics
like risperidone, quetiapine, olanzapine, aripiprazole,
zuclopenthixol, ziprasidone and perospirone in the
management of delirium. These studies suggest that
atypical antipsychotics like olanzapine, risperidone and
quetiapine are as efficacious as haloperidol in reducing
the severity of delirium. Alongside, they also improve the
cognitive functions and are associated with lower incidence
of side effects as compared to haloperidol. A double blind
placebo controlled trial, which compared quetiapine with
placebo showed that quetiapine leads to reduction in the
Table-12: Antipsychotics with recommended doses
Antipsychotics Usual starting dose Monitoring
in patients with
delirium
Haloperidol 0.25 to 0.5 mg Bid Monitor QTc, Extrapyramidal side
effect, DRS-R-98, MMSE/HMSE
Olanzapine 1.25 to 2.5 mg OD// Monitor QTc, Sedation, DRS-R-98,
Bid MMSE/HMSE
Risperidone 0.25 to 0.5 mg OD/ Monitor QTc, Extrapyramidal side
Bid effect, DRS-R-98, MMSE/HMSE
Quetiapine 6.25 to 12.5 mg OD/ Sedation, DRS-R-98, MMSE/HMSE
Bid
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Grover and Avasthi: Management of Delirium in Elderly
severity of non-cognitive symptoms of delirium at a faster
rate than placebo. Although haloperidol is considered as
the most preferred agent in the management of delirium,
but if elderly patients with Parkinson’s disease or Lewy
Body Dementia, develop delirium, atypical antipsychotics
are considered as the preferred agents by a few authors.
Regarding the duration of treatment, there is no consensus.
Some authors suggest that antipsychotics should be
discontinued immediately after the resolution of delirium,
whereas others recommend tapering off of antipsychotics
after a 1-week of asymptom free period.
Benzodiazepines: Benzodiazepines can worsen the
cognitive functions and lead to excessive sedation. Hence,
benzodiazepines are not considered as the first line agent
forthe management of delirium. Benzodiazepines may be
used when the delirium is caused by sedatives or as a result
of alcohol withdrawal or it is associated with seizures.
If benzodiazepines are considered in the management of
alcohol withdrawal delirium then, lorazepam is the preferred
agent, because of its short-half life, lack of major active
metabolites and a relatively predictable bioavailability when
given intramuscularly. When used, benzodiazepines must
be initiated in low doses, especially amongst the elderly,
those with respiratory or hepatic impairment and in patients
receiving medications, which undergo extensive hepatic
oxidative metabolism. It is important to remember that in
general, benzodiazepines are contraindicated in delirium
associated with hepatic encephalopathy as in this condition
there is accumulation of glutamine, which is chemically
related to γ-aminobutyric acid (GABA). If benzodiazepines
are to be used in patients with hepatic insufficiency or
those receiving other medications metabolized by the
cytochrome P450 system, benzodiazepines that get
primarily metabolized by glucuronidation (lorazepam,
oxazepam, and temazepam) should be preferred. In patients
with respiratory insufficiency, benzodiazepines need to be
used with caution. When used, benzodiazepines should not
be stopped abruptly; rather, these must be tapered off.
If delirium in patients with alcohol withdrawal does
not respond to benzodiazepines alone, then use of
antipsychotics may be warranted. However, it is important
to remember that in such a scenario antipsychotics should
be used along with benzodiazepines. Antipsychotics may
be considered when agitation, perceptual disturbances, or
disturbed thinking are not controlled adequately with the
use of benzodiazepines alone.
Data on combined use of antipsychotics and benzodiazepines
in patients with delirium not related to alcohol withdrawal
is limited. Limited existent data suggest that use of
combination may decrease the emergent side effects and
may improve the clinical effectiveness (shorter duration
of delirium, less extrapyramidal symptoms) in special
population, like those with severely ill cancer and AIDS.
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Grover and Avasthi: Management of Delirium in Elderly
In view of role of excess of acetylcholine in pathogenesis of
delirium, some of the studies have evaluated the efficacy/
effectiveness of cholinergic medications in delirium.
The most commonly studied cholinesterase inhibitor is
physostigmine. Other molecules, which have been evaluated,
include tacrine and donepezil. Overall, there is very limited
data for this class of medications.
Effectiveness of highly selective α-2 receptor agonist,
dexmedetomidine, has also been evaluated mainly in
the ICU patients. It has sedating properties (which is
independent of γ-aminobutyric acid receptors), anxiolytic
properties and modest analgesic properties. Further, it has a
very low propensity to cause respiratory depression. Due to
this unique profile, the molecule has been evaluated in ICU
patients with delirium. A review of available studies, which
included 8 clinical trials, of which 5 were Double Blind
Randomized Controlled Trials (DBRCTs), concluded that
dexmedetomidine might be useful in treatment of delirium.
Over the years, melatonin has also been implicated in the
etiopathogenesis of delirium. In view of this some of the
studies have evaluated the role of ramelteon in management
of delirium. Preliminary evidence suggests that ramelteon
may be useful in management of delirium.
Studies have also evaluated the role of paralytic agents
in conjunction with use of mechanical ventilation
for the management of delirium in ICU settings. It
is recommended when patient does not respond to
conventional treatment for delirium in the ICU setting.
This has mostly been tried for patients with hyperactive
delirium, which due to overexertion and fatigue leads
to a hypercatabolic state, which can exacerbate hypoxia
and metabolic abnormalities. Use of heavy sedation
along with morphine improves oxygenation and reduces
skeletal muscle exertion. Use of morphine and other
opioids is also useful in patients of delirium where pain
is a precipitating or acontributory factor. However, it
is important to note that opiates can worsen or cause
delirium, especially those with high anticholinergic
properties.
Electroconvulsive therapy is also rarely being used for
themanagement of delirium. The data is limited toa few
case reports and it can be said that ECT cannot be used as
a substitute for other conventional treatments. Use of ECT
is recommended only in cases of delirium, associated with
neuroleptic malignant syndrome or to patients who have
not responded to all the pharmacological agents.
Discharge from the Hospital and Follow-up
Ideally patients with delirium must be kept in the
hospital until the delirium resolves. Prior to discharge,
family needs to be explained about the any further
management issues and the required monitoring.
S338
As patients with delirium are at a risk of developing
dementia, their cognitive functions must be monitored
from time to time. Past history of delirium also increases
the risk of future episodes of delirium. Accordingly, the
family members must be explained about the symptoms
of impending delirium and what is to be done in such a
situation. Many patients experience significant distress
by recollecting their experience of delirium. They
should be provided with supportive psychotherapeutic
intervention to allay their distress. Even after discharge,
patient and family members must be advised to follow-
up with the psychiatric services for further re-evaluations
and required interventions. In case, such patients are
being managed on outpatient basis, the aim of the
clinician should be to monitor the symptoms in each
follow up by using measurement based care. Alongside, a
close liaison with the primary treating physician/surgeon
must be maintained to promote a joint decision-making
and minimising the confusion.
Prevention of complications of delirium
Delirium can often be associated with secondary
complications like falls, development of bedsores, hospital
acquired infections, functional impairment, problems with
bladder and bowel control and over sedation. Falls can be
prevented by providing care on lower beds or placing the
mattress of the patient on the floor. Wherever possible,
use of physical restraints should be avoided. Because
of prolonged lying down position, especially amongst
those admitted to ICUs, the risk of developing pressure
sores and secondary infections is particularly high in
patients with delirium. Accordingly, patients must be
repositioned from time to time and regularly evaluated
for possible bedsores. Wherever possible, provision of
special mattresses like (water beds) must be considered.
To reduce the functional impairment, patient must be
mobilized at the earliest and in case this is not possible,
adequate mobility must be maintained with the help of a
physiotherapist. As use of catheter for a long duration can
be associated with infections, catheters must be removed
at the earliest and a regular toileting must be encouraged.
Similarly, bowel movement must be monitored to avoid
and constipation.
Prevention of delirium
Considering the fact that delirium is associated with
significant negative health related outcomes, efforts must
be made to prevent the same. The basic algorithm to be
followed for prevention of delirium is given in the figure-2.
All elderly patients or patients of other age group admitted
to medical-surgical ward must be evaluated for their
baseline cognitive functions by using standard instruments
like MMSE, Hindi Mental State Examination (HMSE),
Montreal Cognitive Assessment (MoCA), Abbreviated
Mental Test (AMT) etc. Additionally, the baseline
assessment should involve an evaluation of risk factors,
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Grover and Avasthi: Management of Delirium in Elderly

which make the person vulnerable to develop delirium, in Figure-4: Algorithm for prevention of delirium
the face of further insult. It is of paramount importance to
review the treatment of the patient and all the unnecessary
medications need to be stopped. Other measures include
an adequate pain management, ensuring an adequate
sleep, appropriate hydration and nutrition, a provision of
adequate cognitive stimulation, and minimizing sensory
deprivation by correction of sensory deficits (Table-13).
There is some evidence to support the role of preoperative
consultation and regular daily visits, throughout the period
of hospitalization, by mental health professionals in non-
delirious elderly patients and targeted recommendations
based on a structured protocol to reduce the incidence of
delirium.

Various pharmacological agents used for the management

of delirium (i.e., haloperidol, cholinesterase inhibitors-
donepezil, benzodiazepines, dexmedetomidine etc) have
also been studied for their role in prevention of delirium,
especially in patients undergoing surgical procedures.
The available evidence is inconclusive with respect to
the role of pharmacological agents in prevention of
delirium. A systematic review and metanalysis suggests
that antipsychotics reduce the incidence of post-operative
delirium, mainly in persons undergoing orthopaedic surgery
Table-13: Prevention of Delirium
• Evaluate the cognitive functions at the baseline
• Monitor cognitive functions on regular basis by using MMSE, MoCA,
HMSE, AMT; In case there is a fall in 2 points on various cognitive
function assessment instruments, screen the patient for delirium
• Minimize sensory deprivation (restoration of eyeglasses and hearing aids)
• Stop unnecessary medications
• Minimize exposure to medications which havea high propensity to cause
delirium (anticholinergic) and use alternative agents if possible
• Doses of medications need to adjusted in case patients has impaired drug
clearance
• Weigh the risk and benefit of use of medications with high
anticholinergics properties, opioids and sedatives, especially among
vulnerable elderly patients
• Avoid use of high doses of medications, especially while using
polypharmacy
• Maintain adequate lighting of the area
• Take measures so that patient gets adequate sleep and encourage
normalization of sleep–wake cycles
• Change of rooms must be kept to the minimum
• Frequent reorientation by using visible and verbal queues like calendars,
clocks, familiar objects, providing information about name of the people
around and the role of staff members
• Appropriate cognitive stimulation
• Adequate pain management
• Reduce immobility- encourage independence in activities of daily living
• Explain the patient about any procedures or treatments in simple
language
• Minimize change of staff
• Avoid use of physical restraints
• Quite environment: minimize or remove the unexpected and irritating
noises (e.g., alarms)
• Encourage visits by familiar persons
• Avoid constipation
• Minimise the use of indwelling urinary catheters
and those who are at a higher risk for delirium. The authors
also suggested that there is lot of heterogeneity in the data.
There is some data to support the role of melatonin in
reducing the incidence of delirium among elderly patients
admitted to various medical wards. A recent Cochrane review,
reviewed the available data for prevention of delirium in
patients admitted in non-ICU set-ups. It concluded that there
is no role of of antipsychotics, melatonin and cholinesterase
inhibitors in prevention of delirium. However, the authors
concluded that there is a strong evidence for the role of
supportive multi-component interventions in prevention
of delirium. Currently available guidelines for management
of delirium from various professional organisations do not
recommend use of antipsychotics or other pharmacological
agents for prevention of delirium.
SUGGESTED READING
1. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium
after hip fracture: a randomized trial. J Am Geriatr Soc 2001; 49: 516–22.
2. Fok MC, Sepehry AA, Frisch L, Sztramko R, Borger van der
Burg BL, Vochteloo AJ, Chan P. Do antipsychotics prevent
postoperative delirium? A systematic review and meta-analysis. Int J
Geriatr Psychiatry. 2015;30:333-44.
3. Chen S, Shi L, Liang F, Xu L, Desislava D, Wu Q, Zhang J.Exogenous
Melatonin for Delirium Prevention: a Meta-analysis of Randomized
Controlled Trials. Mol Neurobiol 2016;53:4046-53.
4. Siddiqi N, Harrison JK, Clegg A, Teale EA, Young J, Taylor J, Simpkins
SA. Interventions for preventing delirium in hospitalised non-ICU patients.
Cochrane Database Syst Rev. 2016;3:CD005563.
5. Mo Y, Zimmermann AE.Role of dexmedetomidine for the prevention
and treatment of delirium in intensive care unit patients.Ann
Pharmacother 2013;47:869-76.
6. Miura S, Furuya M, Yasuda H, Miyaoka T, Horiguchi J. Novel Therapy
With Ramelteon for Hypoactive Delirium: A Case Report. J Clin
Psychopharmacol. 2015 t;35:616-8.
7. Tsuda A, Nishimura K, Naganawa E, Otsubo T, Ishigooka J. Ramelteon
for the treatment of delirium in elderly patients: a consecutive case series

Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018 S339

[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]

Grover and Avasthi: Management of Delirium in Elderly

study. Int J Psychiatry Med. 2014;47:97-104. Engelsmann F, Pepin MJ, and Ducic D, Systematic intervention for elderly
8. Kimura R, Mori K, Kumazaki H, Yanagida M, Taguchi S, Matsunaga H. inpatients with delirium: a randomized trial. CMAJ 1994;151:965-70.
Treatment of delirium with ramelteon: initial experience in three patients. 19. Cole MG, McCusker J, Bellavance F, Primeau FJ, Bailey RF,
Gen Hosp Psychiatry. 2011;33:407-9. Bonnycastle MJ, Laplante J. Systematic detection and multidisciplinary
9. Meagher D, Leonard M. The active management of delirium: improving care of delirium in older medical inpatients: a randomized trial. CMAJ
detection and treatment. Adv Psychiatric Treat 2008; 14: 292-301. 2002;167:753-9.
10. Grover S, Mattoo SK, Gupta N. Usefulness of atypical antipsychotics and 20. Canadian Coalition for Seniors’ Mental Health (CCSMH). National
Choline esterase inhibitors in delirium: A review. Pharmacopsychiatry, Guidelines for Seniors’ Mental Health - The Assessment and Treatment of
2011; 44:43-54. Delirium. Canadian Coalition for Seniors’ Mental Health, Toronto, 2006.
11. Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of
Haloperidol, Olanzapine and Risperidone in delirium. J Psychosomatic
Res 2011; 71: 277-81.
12. Grover S, Mahajan S, Chakrabarti S, Avasthi A. Comparative effectiveness This is an open access article distributed under the terms of the Creative
of quetiapine and haloperidol in delirium: A single blind randomized Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
controlled study. World J Psychiatry 2016; 6: 365-71. others to remix, tweak, and build upon the work non‑commercially, as long as the
13. Tahir TA, Eeles E, Karapareddy V, Muthuvelu P, Chapple S, Phillips author is credited and the new creations are licensed under the identical terms.
B, Adyemo T, Farewell D, Bisson JI.A randomized controlled trial of
quetiapine versus placebo in the treatment of delirium.J Psychosom For reprints contact: reprints@medknow.com
Res. 2010;69:485-90.
14. Schrijver EJ, de Graaf K, de Vries OJ, Maier AB, NanayakkaraPW.Efficacy
and safety of haloperidol for in-hospital delirium prevention and treatment: Access this article online
A systematic review of current evidence.Eur J Intern Med. 2016;27:14-23.
Quick Response Code
15. Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, Sanderson
C, Hardy J, Le B, Eckermann S, McCaffrey N, Devilee L, Fazekas B, Hill Website:
M, Currow DC. Efficacy of Oral Risperidone, Haloperidol, or Placebo for www.indianjpsychiatry.org
Symptoms of DeliriumAmong Patients in Palliative Care: A Randomized
Clinical Trial. JAMA Intern Med. 2017;177:34-42.
16. Clinical Practice Guidelinesfor the Managementof Delirium in Older
People. Developed by the Clinical Epidemiology and Health Service DOI:
Evaluation Unit, MelbourneHealth in collaboration with the Delirium 10.4103/0019-5545.224473
Clinical Guidelines Expert Working Group.Commissioned on behalf of the
Australian Health Ministers’ Advisory Council (AHMAC),by the AHMAC
Health Care of Older Australians Standing Committee (HCOASC),
October 2006.
17. Bush SH, Bruera E, Lawlor PG, Kanji S, Davis DH, Agar M, WrightDK,
Hartwick M, Currow DC, Gagnon B, Simon J, Pereira JL. Clinical practice How to cite this article: Grover S, Avasthi A. Clinical Practice
guidelines for delirium management: potential application in palliative Guidelines for Management of Delirium in Elderly. Indian J
care. J Pain Symptom Manage. 2014;48:249-58. Psychiatry 2018;60:329-40.
18. Cole MG, Primeau FJ, Bailey RF, Bonnycastle MJ, Masciarelli F,

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Clinical Practice Guidelines for addressing the Rehabilitation Needs of
Elderly in the Indian context
S.C.Tiwari, Akanksha Sonal
Department of Geriatric Mental Health, King George’s Medical University, Lucknow, sarvada1953@gmail.com
Other Experts Participants: Indira Sharma, Devendra Vijay
Vergiya, MSVK Raju, Gautam Saha
This guideline seeks to summarize available data (including
2006 IPS Guidelines) on healthy ageing and rehabilitation
needs of older adults, with the hope that this knowledge
will help ensure uniform standards of rehabilitation care.
This guideline in no way claims to be comprehensive or
definitive. Mental health professional involved in caring for
this special population group should consider, but not be
limited by the recommendations made herein. Older adults
in different settings need to be cared for in different ways.
In this document we have tried to formulate types of care at
all the possible levels. However, these might not be wholly
suitable for all treatment settings.
This document must be regarded only as a preliminary
effort, especially given the paucity of high level of evidence
worldwide. It is expected that several modifications
and revisions will be required to improve its usefulness.
Hence, inputs and critical comments from mental health
professionals across the country will be more than welcome,
in this regard.
We will be talking about health and ageing with need of
rehabilitation, and then will move onto disease perspective
i.e., from rehabilitation in healthy ageing to rehabilitation in
geriatric mental health illness.
As we have moved from “years to life” to “life to years”,
rehabilitation has become an essential component of
geriatric care and therapy.
1. Foreword
• As per World Health Organization, rehabilitation
intervention should be aimed at achieving following
broad objectives:
• preventing the loss of function
• slowing the rate of loss of function
• improving or restoring function
• compensating for lost function
• maintaining current function
• The goal of rehabilitation in older people, with or
without any underlying psychiatric illness should be
S410 © 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
development of physical independence, and their ability to
do as many daily living activities, as possible.
2.  Problem statement:
• Changing demographics: India is in a state of
demographic transition.
• The improvements in health services have increased
the life expectancy from 33 years (1951) to 69 years
(2011).
• There has been a surge not only in general
population but also in elderly population. The
absolute number of elderly has increased to 97
million in 2017, compared to 12.5 million in 1951.
• Morbidity challenges: Physical and Mental health
morbidity for this population cohort:
• Prevalence of physical morbidity varies from 10-50%
• Prevalence of mental health morbidity is of 20%
Most common morbidity is related to vision (66.5%)
followed by musculoskeletal problems (58.5%), anemia
(43%), hypertension (27.5%), psychological problems (24.5%),
hearing problems (11%) and, diabetes (6%).
• Social Challenges:
• Burden of booming elderly population, especially
from rural India (more than 70 % are hailing from
rural India).
• Most belong to below poverty line, with poor
financial and social support.
• Increasing feminization of the population. (Indian
demographics is not much different from world
demographics)
• Urbanization and migration associated social
change and challenges.
• Nuclear family system.(decreases social support)
• Changing role of females from home maker to full
time office goers.
3.  Healthy ageing: Healthy ageing is a concept promoted by
World Health Organization (WHO), that considers the ability
of people of all ages to live a healthy, safe and socially inclusive
lifestyle. It recognizes the factors beyond health and social
care that have a major effect on health and well-being, and
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Fig. 1: Aspects of healthy ageing
the contribution that must be made by all sectors with an
influence on the determinants of health. Healthy ageing is
a broad concept which includes many aspects of living, as
shown in the figure 1.
Aspects of healthy living:
a) Health and health care: ‘He who has health has hope, and he
who has hope has everything’, is a well known Arabic Proverb.
• Healthy ageing with respect to health care implies,
being able to continue to maintain a healthy lifestyle,
regular physical activity and make accommodations
for any changes in body function, e.g. hearing, vision,
flexibility or strength.
• Continue to engage in routine preventive health
behaviors (e.g. participate in cancer screenings and stay
physically and mentally active).
• Continue to advocate for oneself and one’s family
in health care settings or bring a knowledgeable
representative with oneself.
• Keep an accurate record of all medications with dosing
instructions to review with health care providers.
• Maintain good stress management and emotional
health. Socialization, activity, and access to quality
health care and transportation will all help one remain
healthy, happy and engaged as they age.
b) Legal and financial:
• Careful monitoring of one’s financial resources.
• Examine any work-related benefits, such as social
security or pension.
• Review health care and insurance plans to make sure
coverage is adequate for the needs.
• Continue to consider one’s health care wishes and
discuss these with family members, friends and
physicians.
• Make a plan and leave instructions for any resources
(financial or otherwise) that may survive you.
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Tiwari and Sonal: Rehabilitation needs of Elderly
c) Work life and retirement:
Retirement planning is the process of gathering financial data,
lifestyle information and insight into the three major activities
at retirement: Leisure, Volunteer work and full or part-time paid
work.
• Transition into a less stressful career if one wishes.
Consider a part-time “bridge job” that will not only ease
transition into retirement but also reduce the overall
financial need.
• Become knowledgeable about the continuum of living
arrangements and services available for older adults.
• Go on fact finding trips to scout out places one might
like to live after leaving the workforce, determining the
best fit for later life interests.
• Choose or make accommodations to a home in which
one would want to live even when his physical abilities
decline.
d) Psychological:
• Psychological factors have a powerful influence on the
experience of aging. These influences include one’s identity
and personality, spirituality, personal control, competence,
emotional stability and ability to manage stress.
• Those people who have a sense of involvement in the
care of the next generation, have a positive outlook and
find meaning in life.
• Be mentally and physically active to help preserve
cognitive skills and maintain overall health.
• Maintain ties with friends and family to maximize the
social support system.
• Remain aware of new developments in the arts,
sciences, politics, and other areas of cultural and social
interest.
• If one has religious beliefs, consider how it supports
the understanding of the meaning of life.
‘It’s a time to consider with compassion, new views and lifestyles
of young people even when they clash with our own.’
e) Social roles and resources: Think of yourself as an age
pioneer! Keep up with old interests and develop new ones.
• Develop and maintain those aspects of life which
enhance psychological, social and intellectual well-
being.
• Stable social relations can provide a sense of life-long
continuity.
• Nurture relationships among family and friends that are
most important.
• Change social activities as needed following retirement.
• Develop new relationships that fill gaps created by
losing important loved ones.
• Anticipate and plan for the future—for good and bad
times.
“Our social world is always changing, so plan for and adapt to
that reality throughout our life span.”
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Tiwari and Sonal: Rehabilitation needs of Elderly
4.  Disability and its types: Disability is an umbrella term,
covering impairment, activity limitation, and participation
restriction. Impairment is a problem in body function or
structure; an activity limitation is a difficulty encountered
by an individual in executing a task or action; while a
participation restriction is a problem experienced by an
individual in involvement in life situations. It’s a complex
phenomenon, not just a health problem. It reflects the
interaction between features of a person’s body and
features of the society in which he or she lives. Overcoming
the difficulties faced by people with disabilities requires
interventions to remove environmental and social barriers.
• Various types of disabilities are as follows:
• Physical or movement problems: such as impaired
motor control, loss of limbs, reduced balance,
strength or cardiovascular fitness, fatigue, pain or
stiffness.
• Sensory problems: such as impairment of vision or
hearing, pain, loss of or altered sensation of touch.
• Cognitive or behavioral problems: such as lapses in
memory and attention, difficulties in organization,
planning and problem-solving.
• Communication problems: such as difficulties in
speaking, using language to communicate and fully
understanding what is said or written.
• Psychosocial and emotional problems: such as the
effects on the individual, care giver and family of
living with a long-term condition. These can include
stress, depression, loss of self-image and cognitive
or behavioral issues.
• Medically unexplained symptoms: where a holistic
approach is needed to ensure the best possible
support for both mental and physical wellbeing.
• Mental health conditions: such as anxiety and
depression, obsessive/compulsive disorders,
schizophrenia, eating disorders, post-traumatic
stress disorder or dementia.
5.  Conceptual models of disability:
• NAGI’s model: The first disablement model was
introduced in 1965 by Saad Nagi, who noticed semantic
and conceptual confusion in the disability literature
regarding disability and its associated concepts. Nagi
recognized the importance of the environment and that
family, society and community factors could all influence
disability. Nagi created a model with 4 components:
physiological impairment, functional limitation,
disability and handicap. This model is historical,
however it provided standardized terminology for
disability.
• More recent models of disablement however, have
evolved from the Nagi model in an attempt to better
encompass all the dimensions of disability and the
external factors that influence disablement. Some
adaptations have included the addition of socio-cultural
S412
factors, such as the social and physical environment
and personal factors (including attitudes and lifestyle
behaviors), as well as an emphasis on quality of life and
focus on the interaction between health conditions and
contextual factors. Of particular note is the National
Center for Medical Rehabilitation Research model
(NCMRR) given in 1993. This was revised again in 2006.
• International Classification of Functioning disability
and health (ICF) model: The disablement model created
by the WHO in 1980 has been revised several times
during the last 2 decades. The most recent model is
the ICF, which was introduced in 2001 with the goal of
creating a common international language for disability.
• Bio-psycho-social model: ICF model indicates that
an individual’s level of function (body function,
ability to execute a task and participate in life
activities) is determined by his or her health
condition(s) within the context of environmental
and personal factors.
• The rehabilitation services should target not just
the impairment, activities and participation levels
of the disablement process, but also the personal
and environmental contextual factors that influence
activity and participation.
Thus, effective treatment of late life disability is typically
multimodal.
• Lawton model of environmental press: Ecological,
Person or Environmental fit model.
• Disability results from a mismatch between
individual capacity and task demands, which in turn
are influenced by the environment and the way in
which tasks are performed.
• Remediation of disability occurs through treatments
that either increase individual capacity or reduce
task demand.
Medical or surgical treatments have the potential to increase
capacity. Rehabilitation interventions may improve capacity,
reduce task demands or accomplish both (Table-1: Summary
of the Disability Models).
6.  Assessment of disability in an elderly:
• A systematic approach is useful for the assessment of
new onset or progressive disability in an older adult
(Figure: 2).
1. Characterize the disability — clearly describe the
disability, including its onset, time course and impact
on patient and caregivers.
2. Identify impairments — Initial history and examination
should focus on identifying the physical and psychiatric
issues involved in causing the functional decline or
disability.
3. Identify health conditions — once the problem area
is identified, standard differential diagnostic methods
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Tiwari and Sonal: Rehabilitation needs of Elderly

Table- 1: Summary of the Disability Models

Table: Models of disability
Model’s 0rigin of disability Organ level Person level Society Other domains
level
1.Nagi, 1965 Any Pathology Impairment Functional limitation Disability -
2.a.National Center for Medical Rehabilitation Research, Any Patho - Impairment Functional limitation Disability Societal limitation
1993 physiology (impaired social
involvement)
2.b.National Center for Medical Rehabilitation Research, Any Patho- Organ dysfunction Task performance Roles -
2006 physiology
3.World Health Organization, International Classification Any Health Body structure Activity Participation Environmental and
of Functioning, 2001 condition and functioning personal factors
4.Lawton Environmental fit/press Model Mismatch between individual capacity and task demand Environmental and
personal factors

Appendix contains commonly used assessment tools for quick

assessment{(Physical cognitive balance screening test, Activities
of daily living (ADL) and Instrumental activities of daily living
(IADL)}.

7.  Approach to management of disability in an elderly:

Fig. 2: Flow chart for assessment of disabilities in elderly
are used to identify the specific health conditions
underlying or contributing to the patient’s disability.
4 Identify contextual factors — Understanding patient’s
physical environment, social support, and financial
resources is important in developing a feasible
management plan.
• A comprehensive assessment of elderly is necessary,
with focus on availability and accessibility of resources,
affordability and acceptability of the patient and care
giver. Important points for this are:
• Perspectives of both the patient and caregiver are
important to consider.
• A brief screening test for physical and cognitive
impairment should be performed in a patient with new
or progressive disability, even if the patient does not
endorse memory problems.
• When feasible, a home visit is the best way to
understand how the patient functions within his or her
environmental and social context.
• Physical or occupational therapy (OT) home health
assessments or other community programs may help to
accomplish this.
• In patients with multiple health conditions, it is
frequently impossible to identify a primary cause
or trigger for the disability. Rather, identifying all
contributing conditions, impairments and contextual
factors and addressing these factors with appropriate
interventions is the most effective means of reducing
functional dependence.
• Once the underlying health conditions, impairments
and contextual factors are understood, a practical
management plan can be developed with the patient
and family.
• These plans generally include strategies to enhance
functional abilities (i.e. improve capacity), decrease
functional demands (i.e. reduce demand), or both
(Figure: 3).
• Strategies to improve capacity — clinician should
identify ways to improve the patient’s capacity to cope
with physical and environmental challenges.
a)  Medications, e.g.:
• Oxygen or cardiac medications to improve
hemodynamics in patients with heart failure
• Antidepressants for patients with depression
• Analgesics for chronic pain
Discontinuing unnecessary medications that may have
adverse side effects (e.g. chronic use of proton pump
inhibitors has effects on cognition and bone health).
b)  Surgery, e.g.:
• Cataract excision to improve visual capacity
• Joint replacement in disabling arthritis
c)  Nutritional intervention, e.g.:
• Weight loss for obesity
• Nutritional supplements when nutrition is impaired
d)  Exercise, e.g.:
• General physical activity to improve aerobic capacity
• Targeted exercises to address a specific impairment
(e.g. range of motion and strengthening exercises for
knee)

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Tiwari and Sonal: Rehabilitation needs of Elderly
Fig. 3: Approach to management of disability in elderly
e)  Prosthetics and assistive devices, e.g.:
• Hearing aids
• Artificial limbs
• Ankle orthosis
f)  Neuropsychological rehabilitation, e.g.:
• Cognitive training
• Reality orientation
• Emotional retraining
• Strategies to reduce demand — If the patient’s
capacity for physical function cannot be sufficiently
improved by treating the underlying health
conditions and/or use of interventions such as
exercise alone, then strategies to reduce the task
demands should be considered.
a) Environmental modifications, e.g.: Adding railings,
High contrast/low glare lighting
b) Assistive devices and adaptive equipment, e.g.: Walkers,
Reaching aids, Tub/shower chair, Raised toilet seat
c) Increasing human help, e.g. referrals for: Home health
aide, Assisted living environment, Driving services,
Meals on Wheels
d) Adaptive training to help patients learn strategies to
reduce demand, e.g.: Low vision rehabilitation, Energy
conservation techniques
• Care of the caregiver – Informal, lay caregiver or primary
caregiver is still the anchor of the rehabilitation process
in developing countries. Their needs and problems are
still highly neglected. A large majority of caregivers
experience fatigue, frustration, and stress as a result
of care giving. Family members and other providers
often accept responsibility for the care of those with
chronic health needs. As time and illness progress, the
responsibility may be met with decreasing enthusiasm,
and caregivers may find themselves angry or resentful
about this toll on their lives. Important aspects in
assessment and management of care givers are:
a)  Assessment of causes of burnout or burden.
b)  Training programs for caregivers. (Table-2: Summary of
Different Management Strategies).
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Table-2:Summary of Different Management Strategies
Objectives Of Domains Techniques
Rehabilitation
Improve Physical Medications, surgeries, nutrition, exercise,
capacity assistive devices if required
Psychological/ Early identification and management of
mental mental health problems, positive mental
health(meaning in life), spirituality,
cognitive rehabilitations
Reduce Environmental Adding railings, High contrast/low glare
Demand modifications lighting, Supportive toilets, low furniture
arrangement, non slippery floor, ramp, short
comfortable staircase if required
Assistive Walkers, Reaching aids, Tub/shower chair,
devices and Raised toilet seat
adaptive
equipment
Increasing Referrals for: Home, health aide, Assisted
human help living environment, Driving services,
Meals on Wheels e.tc
Adaptive Low vision rehabilitation, Energy
training to conservation techniques
help patients
learn strategies
to reduce
demand
Care for the Psychological Psychoeducation, emotional support,
Caregiver ventilation, stress management,
counseling, problem solving techniques,
pharmacological and non pharmacological
help, comprehensive training programs
Physical Formal medical help, easy referral
system
Financial Social security schemes, income tax
rebates, concessions, pension schemes
Social De stigmatization, social support, elderly
friendly society, park theaters shopping
complex,
8.  Multidisciplinary approach to rehabilitation:
• Rehabilitation in elderly needs multidisciplinary
approach keeping patient and care giver at the focus.
• The geriatric mental health professional needs to liaise
with a host of various specialists to device treatment
strategies. This need for multidisciplinary approach is
depicted in figure: 4.
There is a defined role for each of these specialists.
• Clinical psychologist: Assessment and management
of cognitive and behavioral problems, via cognitive,
psychological and behavioral retraining. This is helpful
especially for those who cannot or will not tolerate
medication, are dealing with stressful interpersonal
difficulties, have limited level of social support or have
recurrent episodes of mental illness.
• Nutrition therapist or dietician: Frailty as well as obesity
should be targeted in time to prevent its long term
consequences in form of fall factures, bed ridden, loss
of independence and cognitive deprivation. Nutrition
and physical activity are two important determinants of
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Fig. 4: Multidisciplinary approach towards rehabilitation
physical as well as mental health. Mental and physical
health has a complex interplay with nutrition and
physical activity, as shown in fig. 5.
For e.g., in dementia omega 3 fatty acids are protective or
moderate alcohol intake may be protective for dementia
which in turn may be caused by heavy drinking.
Illness per se effects nutritional status, e.g. in early phase
of dementia there may be inability to prepare and procure
food; leading to nutritional deficiency. During later stages
there may be inability to consume sufficient oral meal.
Other conditions like depression, bipolar and other
situational conditions (mood disorders: bereavement and
loneliness), may cause decrease intake, leading to fraility,
cachexia and anorexia.
• Physiotherapist: Helps in assessment and management
of mobility related issues of elderly. Interventions
can be in form of aerobic exercises, yoga, and muscle
strengthening activities to increase flexibility and
improve balance. Development and implementation
of an activity plan should be tailored according to
individual capacity.
• Occupational therapist: They plan various activities for
the behavioral and cognitive stimulation of the patients.
These should be individualized and based according to
the resources available.
• Psychiatric social worker: Helps in evaluation of the
materialistic and manual resources of the subjects.
Provides psycho education about the illness. It should
be low and dose dependent. Family therapy is important
component in geriatric rehabilitation. Important
reminders are:
o Family care is an adaptive challenge
o Family rarely has one voice
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Tiwari and Sonal: Rehabilitation needs of Elderly
D P
P
M
Fig. 5: Role of nutrition and physical activity on mental health
o Few have only one to care at one time
o There is no one way or ideal way of family care
o Successful caregivers are flexible in adjusting to
expectations of themselves and the patient
o Caregivers awareness to available services is
important
o It is better to help them develop their way of
handling situations
o Denial is common defense in caregivers to provide
hopeful consistent daily care
o Help them understand and develop contingency
plans
A social worker also help caregivers with different
government and non-governmental information’s, which
will be of help to them i.e., pension scheme, income tax
rebate, e.t.c.
• Spiritual healer: Spirituality has been conceptualized
as including an individual’s transcendent relationship
with a higher being or with the universe and has been
positively linked to hope, coping and religiosity. It has
been found to be particularly important among older
adults and positively linked to self-appraised good
health among elders.
• Psychiatry nurse: Psychiatry nurses work in
collaboration with older adults, their families, and
communities to support healthy ageing, maximum
functioning and quality of life.
• Recreational therapist: Assessment and management
of leisure preferences, adaption and integration into
therapeutic plan e.g., art therapy or music therapy.
• Helper: could be either a ward boy or a family member,
who fits the role of support staff.
• Others: These may be in the role of Orthotist,
Prosthetist, Optometrist, Speech therapist, and other
specialists as needed.
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Tiwari and Sonal: Rehabilitation needs of Elderly
9.  Planning a rehabilitative strategy:
Aims of the rehabilitation program are:
• To make the life of elderly more meaningful and
dignified.
• To help them to be as much self-sufficient as
possible.
• To improve the overall quality of life by enhancing
and ensuring optimal utilization of their preserved
abilities, minimizing the need of their lost abilities
and providing necessary assistance for better
functioning.
• Following are the steps of planning a comprehensive
rehabilitation program for an elderly (Figure: 6)-
• Establish a rapport and a therapeutic alliance with
the individual and his family members or caregivers.
In order to get maximum benefit from the program,
it is absolutely essential that the family members
have understood the need for the program.
• Assessment of impairment: rehabilitation program
has to be tailor made for each individual and so it
will have to be planned depending on the nature
and extent of impairment with due focus on the
activities of daily living.
• Having assessed the impairment, one would like to
develop strategies to overcome it. In order to do
so, one would need to know about the available
resources in the form of manpower (caregivers:
trained/untrained), availability of rehabilitation
centers, day-care centers, the medical and
paramedical staffs and financial resources.
Plan should be affordable, easily available, accessible and most
important acceptable for the care giver.
• Charting out a rehabilitation program: a comprehensive
rehabilitation program would include certain common
general measures which one would like to observe
for all the patients and specific measures which are
specifically tailor made for a particular patient.
Common general measures:
• Maintain daily rhythm and daily schedule.
Fig. 6: Steps for planning a rehabilitation program
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• Maintain orientation to time, day, date, month, year,
touch with recent events and new developments.
• Maintain active participation in routine and
extracurricular activities.
• Practice to use of new devices, gadgets and instruments.
• Make provisions for easy and well supported mobility.
• Avoid frequent change in home and living arrangements.
• Adapt an active life, and never retire.
• Small frequent meals.
• Easy to wear clothes, toiletry needs.
• Reduction to complete stoppage of substances like
alcohol-tobacco etc, regular sleeping pattern.
Specific Measures: These measures can be implemented at
home with the help of relatives or community health workers,
under supervision of a mental health professional, at the
memory clinic or day-care-center with the help of trained staff,
or at the residential care facility where the patient is staying.
• Cognitive retraining: may be utilized to help the
patients having cognitive deficits in various areas. This
may improve some of the cognitive skills of the patient
and may prevent or at least slow down the further
decline in cognitive abilities.
a) To improve the memory function: Patients may be
asked to keep a memory aids, sign boards. Patients
may be taught other methods to remember things like
using mnemonics or using retrieval clues to remember
certain things which patient wishes to remember. As an
exercise to improve memory patient may be encouraged
to play ‘playing card memory game’ or memory games
on computers.
b) To improve visuo-spatial orientation: Patients having
problem in visuo-spatial orientation may get lost
while traveling. A therapist can escort the patient
on his traveling route and help him to recognize and
remember certain landmarks and clues which will help
patients to travel independently. Patient may also be
given a cardwith a map and directions on it to carry
with him. In case of difficulty in finding a way, he may
show the card to a policeman or a shopkeeper and get
the direction from them.
c) To improve executive functions: Planning, organizing,
decision making may be compromised in old age.
Various games like Ludo, Chess, Draft, Chinese-checkers,
puzzles, card-games etc. require these skills. Playing
these games help in improving executive functions.
• Motor retraining:
a) To improve speed, accuracy and coordination: Many of
the computer games improve our speed and accuracy.
Usually these games have different levels. Playing these
games regularly may improve the speed, accuracy and
coordination. Activities like drawing, painting, craft or
sculpture making also enhance these skills.
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Table-3: General Strategies for planning and execution
of rehabilitation in elderly
Objectives Strategies Interventions
General Maintain Set fixed time for all the daily routine
measures biorhythm like time to wake up, toilet, exercise,
have meals, naps, TV watching,
temple or hospital, evening walk etc.
Activities should be charted, penned and
if possible displayed in patient room. All
should be taught about sleep hygiene.
Avoid day time naps, and use of
sedatives and hypnotics.
Dietary Small frequent meals should be advised,
scheduling rich in proteins, fibers and low in fats.
Adequate fluid intake must be assured.
Special care should be taken with
edentulous older adults. Dietician advice
can be taken when and where required.
Completely avoid or at least reduce use
of substances like-alcohol, tobacco etc
Clothing Healthy older adults can maintain
their dressing style as they like. But
in compromised older adults preferred
dressing will be easy to wear one piece
comfortable linen which is easy to put
on and off.
Elderly Bathrooms-non slippery, rough non
friendly home skid tiles, adequate lighting, hand
environment support along the toilet seat and
bathing area, hand shower if possible.
Others- Minimal furniture, avoid dim
or flashy lights, clean-well lit-railing
supported corridors, things of daily use
should be kept within range, provided
with walker, tripod stick when necessary.
Toiletry needs Major case of attenders distress, they
and habits should be educated about urinary
and bowl problems of old age, need
for appropriate medical and surgical
corrections(i.e prostate), cortical
incontinence of late stages of dementia
and use of diapers and care associated.
Orienting Newspaper reading, TV/Radio
patients with programs, Wall clocks or mobile apps
time, date, day, with verbal effects, calendars, frequent
month, year use of day date time in communication
Orientation to Newspaper, TV, radio, socializing with
recent events and friends and relatives. Encourage and
new development motivate them to involve in as many
household activities like- what cock?
how to cock? festival plans? travel
plans? Etc- as possible.
Participation in Religious- regular visits to place of
various activities- worship, satsang, sundarkand/geeta/
religious, family, ramayan path.
social Family-wedding ceremonies,
exhibitions, small get together when
and where possible.
Extracurricular- help them to
develop or reinvent their hobbies like
sports, painting, reading or writing,
singing, learning to play new musical
instruments or new games
Help and encourage them for
developing social network of their own
Contd...
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Tiwari and Sonal: Rehabilitation needs of Elderly
Table-3: Contd...
Objectives Strategies Interventions
Learn to operate To enhance their independence
new devices, encourage them to learn how to
gadgets and use mobiles, simple appliances like
instruments heating kettles, remote control for
tv/ac etc by simplifying the steps
and color coding required buttons,
providing important contact numbers
written and pasted on wall near phone
or mobile, not to confuse them with
excess complex information.
Adequate Never retire-continue to work full time
cognitive or part time as possible, at least under
engagement supervision if not independently -
make work place elderly friendly.
This will help them have worth,
meaning and purpose in life and to
maintain their self esteem.
Table-4: Specific Strategies for planning and execution
of rehabilitation in elderly
Objectives Strategies Interventions
Cognitive Memory function Memory Diary, memory note, family tree, sign
retraining board(kitchen, bed room, bathroom), mnemonics,
retrieval clues, memory games like-playing cards,
suduku, puzzles and many more computer based
games, frequent revisions of facts and review of
albums and photo about the people and places.
Most important never to discourage or humiliate
them if they go wrong rather encourage and
motivate them for their efforts.
Visuo-spatial Analyze the level of difficulty- break the
orientation path with certain landmarks and cues to help
patients. Advice for guide map with detailed
address mentioned with them for use if
required.
Executive function Various games can be used- ludo, chess, draft,
business, Chinese checker, puzzles, card games
online or offline. Other way can motivate them to
plan and organize small get together, functions or
group activities.
Motor Speed, accuracy, Activities like gaming indoor or outdoor, online
retraining coordination and offline, drawing, painting, craft, gardening,
sculpture-making, playing music instruments like
guitar, sitar, table etc
Mobility Static exercises like yoga and dynamic
exercises-walking, jogging, aerobic exercise
improve mobility.
Outdoor games like-volley-ball, hand-ball etc
use of prosthesis and walking devices, body
massages.
Emotional Improve self esteem In spite of reminding them of their limitations
retraining encourage them about their abilities, let them
carry out activities of their interest as much as
they can. Make them feel as asset and not as
burden.
Challenging Define decode devise determine the
behavior challenging behavior. Use behavior therapy
with learning of acceptable behavior and
unlearing of unacceptable behavior. Use
distraction, indifference token economy etc
Expressed emotion Be Overprotective or overcritical both are
of caregiver harmful for the patient. Psychoeducation,
counseling will help in handling this issue
successfully.
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Tiwari and Sonal: Rehabilitation needs of Elderly
b) To improve mobility: With the advancing age and
especially due to motor or sensory neurological
deficits the mobility is very much compromised. Static
exercises like yoga and dynamic exercises like walking,
jogging, aerobics may be utilized to improve mobility.
Participating in outdoor games like volley-ball, hand-
ball etc may also be very useful. If required one may
use various prosthesis and walking devices to improve
the mobility. In past good body massage was used to
rejuvenate the body and improve the mobility.
• Emotional retraining:
a) To improve the self-esteem and feelings of being a
useful member of society: One of the most important
parts of the rehabilitation program is to improve the
self-esteem of the elderly individuals and make them
feel that they are still very important and useful
members of the society. Whenever appropriate, the
family members should treat them as the heads of the
family and seek their opinions, advice and guidance.
They may be given some responsibilities according to
their interest and abilities.
b) To improve challenging behavior: Occasionally elderly
individuals may show childish behavior or disinhibited
behavior. One may have to deal appropriately using
principles of behavior therapy in these kinds of
situations.
c) To improve adverse attitudes of family members &
to provide support to family members: Some family
members may be overprotective and may not allow
the elderly individual in the family to do anything by
themselves. On the other hand some family members
may be overcritical and keep on condemning the
elderly without realizing that the unusual behavior
is not intentional but is due to cognitive deficits. In
such situations, counseling the family members is
very essential for the effective implementation of the
rehabilitation program. (Table-3 and 4 Summary of
strategies for planning and execution of rehabilitation
in elderly).
Important issues while planning a rehabilitation program:
• Rehabilitation program should be planned and
implemented as early as possible.
• The program should be comprehensive and tailored
to help the individuals to overcome the practical
difficulties in day-to-day life considering socio-cultural
environment and urban or rural background.
• As one may not be able to implement and achieve too
many things simultaneously, it may be a good idea to
decide one or two priority-goals at the beginning in
the rehabilitation program and work on the other goals
after achieving the priority goals.
• Look around, think, ask, discuss and you may find an
innovative solution to a problem.
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• One may have to modify the rehabilitation program
from time to time according to the changing needs of
the persons.
• Be vigilant about the masked deficits: these are the
deficits which may get unmasked when the individuals
face more challenging circumstances.
• Take into account the other associated problems: many
of the senior citizens may have visual and auditory
problems. They may also have other medical problems
like arthritis, heart disease, diabetes, hypertension,
nutritional deficiencies etc. One of the important issues
to keep in mind is ‘elderly abuse’.
• While providing the various facilities in a rehabilitation
program one should strive to attain the best possible
quality of care for our elderly individuals (Figure-7:
Steps to be followed in planning of rehabilitation and
it’s follow up).
10. Levels of care and rehabilitation:
Rehabilitative strategies could be implemented through
community based approaches, institution based approaches
or through outreach programs.
• Community based rehabilitation: This is a strategy
of developing rehabilitation services in the community,
to provide equal opportunities to all. It attempts social
integration of those in need of rehabilitation. There is a
collective effort of disabled, family and community.
• Institutional based rehabilitation: disabled
persons are provided training in hospitals/ rehabilitation
centers. These function as referral center for community
rehabilitation center.
Figure 7: Plan to be followed
Societal
level
Tertiary care
–research centre
District
hospital/medical
college
PHC/CHC
Home
level
Fig. 8: Levels of health care facilities involved in rehabilitation
in elderly
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• Outreach programs: The experts from hospital visit
the community or home for providing education and training
to disabled in self care, ambulatory effect, communication,
vocational guidance. Camps are also organized from time to
time in rural area where community facility is not available.
There is need to integrate community rehabilitation centers
with institutions to provide maximum rehabilitation
coverage to all parts of the country.
These programs depend on health set ups/centers to deliver
care. Different communities have different structure of
health care facilities which cater to the need of rehabilitation
in elderly. Figure -8: Shows the hierarchy of health care
system in India.
Rehabilitative measures at individual level:
• Home assisted care: For those individuals who cannot
visit the day-care center, community health workers
pay home visits to provide the necessary help to the
patients and relatives. These are supervised by a mental
health professional.
• Daycare center: These serve the same purpose in elderly
which the school serves in children. Occupational
therapists, physiotherapist, and counselors can take
classes for them. They will make them sing songs and
recite poems, read-out stories to them and give them
lessons in drawing, painting and craft. Senior citizens
will also receive a sumptuous afternoon meal and
supervised dose of medication.
• Residential care facility: Senior citizens, who are unable
to lead an independent life in their own homes, may
require residential care facility. Senior citizens having
dementia may also require hospitalization or residential
care facility when they develop delirium and behavioral
and psychological symptoms associated with dementia
(BPSD). Frequently, these patients may have to be
restrained and require sedatives and tranquilizers which
sometimes may further worsen their situation. In order to
provide better facilities to elderly patients and to those
who require short-term or long-term hospitalization
or institutionalization it is desirable to have good
residential care facilities. Cognitive enhancers (Donepezil,
Rivastigmine or Galantamine) and psychotropic
medications may be sparingly used in the residential care
facility. If a patient gets agitated or restless, instead of
sedating him or tranquilizing him, he may be pacified using
behavioral techniques in a nonthreatening environment.
Though these setups are mostly unavailable in India but
it is the need of the hour to have such facilities in India to
cater the needs of growing population of elderly.
• Self-help groups: A group of senior citizens can start a
self-help group. This group, like other self-help groups,
can meet on regular basis and help the other senior
citizens and organize various activities for them on a
regular basis.
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Tiwari and Sonal: Rehabilitation needs of Elderly
HelpAge India has felt that field models have to be
initiated to address this grave situations where in elders
can be Sensitized/facilitated and capacity built to make
themselves sustained and help their own peer groups and
make themselves occupied. In this process, Elder Self Help
Groups under Comprehensive Age Care Models started in
the year 1999 to bring all the Active Poor Elders together on
a single platform to encourage a social bonding and thrift
practice among themselves. Today HelpAge has created
3241 Comprehensive Elder Self Help Group models in 20
States on PAN India basis, which are catering to varied
needs of poor active elders as below. Develops strong we
feeling and emotional support. Elders help each other in
accessing all types of Resources like Govt Schemes, Health
facilities, local market linkages. The Elder Group members
provide counseling to their own group members and also to
other elders living in their community in cases like death,
family disputes etc. Internal Group Lending helps Elders to
design small business models for Petty Business purposes
and these results in achievement of Self Sustainability of
Elders. Group members are able to re-join their families and
Communities because of increased Financial Sustainability
and Dignity of life
• Psychiatric Intensive Care Unit (PsylCU): There should
be provision for Psychiatric Intensive Care Unit (PsylCU),
and rooms for terminally ill patients who are bedridden.
These patients are not supposed to spend their 24
hours in the bed waiting for their last breath, and
should engage in recreational activities, as feasible.
Rehabilitative measures at societal level:
At the societal level, special provisions should be made for
accommodation, mobility, transportation, recreation and
financial assistance for elderly.
• Special provisions for accommodation: Senior citizens
should have access to accommodation, on individual or
on group basis.
• Special provisions to enhance mobility and for
transport: To facilitate the mobility and journey of senior
citizens special amenities should be made available on
the road, on the station, at other public places. Some
seats may be reserved in the buses and trains for elderly
individuals; there may be separate queues at the ticket
windows and elevators & escalators at the shopping
centers and movie theatres.
• Financial assistance: Financial assistance in various
forms such as pension, tax-rebate, soft loans, special
interest rates and investment plans may be provided
to improve the quality of life of our needy elderly
individuals. Section 80DDB of the income tax act allows
a medical expense deduction of up to Rs. 40,000 from
the taxable income of patients with dementia. The
maximum deduction permissible is Rs. 60,000 in the
case of patients aged 65 years and above. If the patient
is not an income tax payee but is the dependent of a
caregiver who is income tax payee, the caregiver can
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Tiwari and Sonal: Rehabilitation needs of Elderly
claim the deduction. To be eligible for the deduction,
the level of disability resultant from the dementia
should be at least 40%.
• Special provisions for recreational activities: Dedicated
recreational places like “senior citizen parks” are
coming up in some of the cities in India.
Special issues in rehabilitation:
• Marriage, divorce and live in relationship: Even senior
citizens have right to get married if they are single or
have lost their spouse. They have a right to ask for
divorce if they are unable to happily stay together; and
they also have a right to enter into a live-in relationship.
As the needs of the elderly population increases, one
may have to have marriage bureaus for them and special
counseling centers and courts to deal with divorce
applications filed by them.
• Foster families: The concept of foster family may work
both the ways for senior citizens. They may either adopt
a needy young individual or a couple and provide them
accommodation, food and financial assistance in lieu of
physical and nursing care provided by them or the young
and working couple may adopt the elderly individuals
or a couple and provide them accommodation, food
and financial help in lieu of housekeeping and childcare
provided to their children by the elderly individuals.
• Legal will and advanced directives: Making will or
giving advance directives about artificial sustenance of
life or carrying out certain religious ceremonies after
their death are some of the issues which get importance
at this stage of life. Discussion at an individual level or
in group may be very helpful for the clarity on these
issues.
• Security: The elderly are prone for robbery, theft,
manhandling and at risk of life by antisocial elements.
Thus, this issue should be focused and addressed.
11. Rehabilitation in geriatric mental illness:
Principles of rehabilitation in an elderly in presence of
mental illness remain essentially the same, as for a healthy
elderly. Thus far we have discussed rehabilitation needs of
healthy elderly. This part of guideline will discuss specific
requirements for rehabilitating an elderly with mental
illness.
— Purpose: Restore and maintain the highest level of
psychological, physical and social function despite the
disabling effects of illness.
— Goal: The goal of management is to improve the quality
of life for patients and caregivers, maintain optimal
function and provide maximal comfort.
Disabilities associated with geriatric mental illness are:
• Primary disability: Cognitive, emotional, motivational,
behavioral
• Secondary disability: Loss of self confidence, social
withdrawal, loss of social role and negativism
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• Tertiary disability: Homelessness, poverty, social
stigmata
Therapeutic (curative) and prosthetic (supportive and
rehabilitative) approach should go hand in hand.
Principles of rehabilitation in geriatric mental illness:
— Focus on treatment at home, or close to home
— Ensure comprehensive assessment
— Encourage normal function
— Treat the treatable
— Analyze disabilities and chart progress
— Clarify team goal with patient, caregiver and support
workers early
— Teach what can be relevant
— Adapt the adaptable
— Coordinate support and follow up
— Promote flexibility, ingenuity with realistic optimism
Approach for rehabilitation in this sub group should be
multi-disciplinary, with need to liaise with primary care
team, specialist psychiatric team, social workers and local
authorities. The medical, social, financial and spiritual
support system needs to be even more robust when dealing
with elderly with mental illness.
— Indications of rehabilitation in geriatric mental illness:
• Individuals having mild cognitive impairment.
• Individuals having mild, moderate or severe dementia.
• Individuals having neurological deficits.
• Individuals having BPSD (Behavioral and Psychological
Symptoms of dementia).
• Individual with impaired Activities of daily living (ADL).
Rehabilitation needs in special conditions (Special focus
on dementia):
Most elderly requiring geriatric mental health rehabilitation
residing either in home, community or in a hospital set up
suffer from cognitive complaints.
In adult population, rehabilitation in psychiatry is
synonymous with long term Schizophrenia care. However,
Fig.9: Neuro-cognitive Deficit Disorder
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Tiwari and Sonal: Rehabilitation needs of Elderly

in old age, mental health problems other than dementia, Definitive treatment:
like psychosis of late life, depression, bipolar affective • There is currently insufficient evidence to recommend
disorders, situational disorders have good response to the use of Cholinesterase inhibitors in mild cognitive
pharmacological and non-pharmacological treatments. impairment.
Thus need of rehabilitation in these ailments is very rare. • There is currently fair evidence to recommend against
the use of Nonsteroidal anti-inflammatory drugs in mild
Hence here we will be discussing about rehabilitation in cognitive impairment.
cases with neuro-cognitive complaints. It can be further • There is currently fair evidence to recommend against
categorized in three groups as depicted in figure-9. the use of Estrogen replacement therapy in mild
cognitive impairment.
a) Mild Neuro-Cognitive disorder/cognitive impairment • There is currently fair evidence to recommend against
(No dementia): the use of Ginkgo biloba or Vitamin E in mild cognitive
This group is vulnerable for future cognitive decline impairment.
(conversion rate of 5-20%), so there is need to address this
group for primary prevention. Psycho-education about the b)  Mild to Moderate Dementia-
services available, risk of disease progression and need Recommended actions to assist patients with mild to
of structured pharmacological and non pharmacological moderate dementia:
interventions is essential. Advice about advanced directives — Inform patient and family of the diagnosis
should be given when and where required. — Identify the caregiver and his/her needs
— Referrals, as needed
Non-definitive treatment: — Assess for safety risks
• Cognitive interventions — Determine presence of any advanced planning
There is fair evidence that physicians and therapists should document
promote engagement in cognitive activity as part of an — Assess patient’s decision making capacity
overall “healthy lifestyle” formulation for elderly individuals — Inform about pharmacological and non-pharmacological
with and without memory loss. treatment options, and research studies available
— Develop and implement a treatment plan with defined
• Physical exercise goals
There is fair evidence that physicians and therapists — Assess and manage behavioural and psychological
should promote physical activity, at an intensity level that symptoms of dementia
is adapted to the person’s overall physical capacities, as — Monitor response to therapy
part of a “healthy lifestyle” for older individuals with and — Monitor and manage functional problems
without memory loss. — Monitor nutritional status
— Provide ongoing medical care
• Treatment of vascular risk factors: As vascular risk — Mobilize community based and facility based resources,
factors and co-morbidities impact on the development as needed
and expression of dementia, they should be screened
for and treated optimally in patients with mild cognitive Table 5: Strategies and techniques for cognitive
impairment. rehabilitation:
• Treating hypertension: There is good evidence to c)  Severe Dementia-
treat systolic hypertension (> 160 mm Hg) in all older General approach to the management of patients with
individuals. In addition to reducing the risk of stroke, severe dementia
the incidence of dementia may be reduced. The target — Patients should be monitored closely by health
systolic blood pressure should be 140 mm Hg or less professionals
There is some evidence that treating hypertension — Monitoring should involve assessment of the patient’s
may prevent further cognitive decline associated cognition, function, behavior, and medical and
with cerebrovascular disease. There is no compelling
Table-5: Rehabilitative interventions and strategies for
evidence that one class of agent is superior to another;
mild-moderate Dementia
calcium-channel blockers or angiotensin converting-
Guiding principles Recall strategies Specific interventions
enzyme (ACE) inhibitors may be considered.
• Antiplatelet therapy with acetylsalicylic acid: There is Effortful processing Mnemonics Face- name recall
Dual cognitive Cueing Number recall
currently no evidence to support the use of acetylsalicylic support Chunking Story recall
acid to specifically treat dementia associated with Errorless learning Method of loci List object recall
cerebrovascular disease. Acetylsalicylic acid or other Spaced retrieval Procedural memory
antiplatelet therapies should be used for the prevention Fluency training
of recurrent ischemic stroke in appropriate patients. Semantic impairment

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Tiwari and Sonal: Rehabilitation needs of Elderly

nutritional status, as well as the caregiver’s safety and Table-6: Barrier’s in Rehabilitation and Bridges to them
health S. No. Domains Barriers Bridges
— The goals of management are to improve the quality 1. Illness Stigma attached De stigmatization- increasing
of life for patients and caregivers, maintain optimal related awareness , IEC activities
function and provide maximum comfort factors Cognitive deficit as Cognitive remediation and
basic component cognitive retraining
Denial of illness Psycho education, focus on
Medical management includes treating intercurrent medical how symptoms and disability
conditions (e.g., infections, Parkinsonian symptoms, interfere with personal goal
seizures or pressure ulcers), ameliorating pain, improving Refusal of treatment Motivational interviewing,
identifying reinforces
nutritional status and optimizing sensory function. Start where patient is at present
Passivity and apathy
associated and use behavior therapy, keep
Patients should be monitored closely by mental health reinforcing small steps.
professionals. Monitoring should involve assessment of 2. Treatment Poly pharmacy Simplify drug regimen give
related simple instructions
the patient’s cognition, function, behavior, medical and Drugs related side Start low- go slow- go long,
factors
nutritional status. Also assess caregiver’s safety and physical effects and adverse involve care givers in shared
and mental health. events decision making, smooth
referral services when and
where required
Specific intervention for severe dementia involves Poor compliance and Psychoeducation and adequate
principally motivation based techniques follow up involvement of caregiver in
• Stimulation of island of preserved cognition, decompose the long term treatment plan
Poor service Community Outreach
complex task in simple task
availability programs/telepsychiatry
• Presentation of increasing complex task 3. Caregiver/ Associated nihilism Psychoeducation, involve
• Potentiating of brain plasticity Family and poor attitude them in awareness programs
• Induce use of implicit way of functioning related help them understand elderly
• Implicit orientation, improved functioning and well factors are asset to them rather
burden, help of groups like
being HelpAge India or NAMI
High expressed Psychoeducation, one to one
12.  Barriers in rehabilitation: emotion behavioral family therapy,
Following are barriers in instituting a rehabilitation strategy multiple family group therapy
Poor communication Teaching caregiver skills to
effectively: and stress intolerance handle small behavior issues
• Lack of strategic planning effectively by engaging them
• Lack of resources and health infrastructure in something they like i.e
• Lack of agency responsible to administer, coordinate, music, art, gardening, reading,
pet care.
and monitor services Feeling of loss of Involve caregivers from
• Inadequate health information systems and control on progressive the beginning in long term
communication strategies deterioration of the treatment plan-“Hope for the
• Complex referral systems limiting access patient best and prepare for the worst”
4. Therapeutic Therapeutic nihilism Improve training in geriatric
• Lack of engagement with people with disabilities mental health issues; expose
alliance by clinician and poor
related attitude them to successful beneficiaries
Bridging the barriers: factors of mental health services.
These barriers to rehabilitation can be overcome through a High expectations and Use person-centered, recovery
oriented approaches (patient is
series of actions. These include:
always right)
• Reforming policies, laws, and delivery systems Time constrain Provide them with structured
• Developing funding mechanisms: financing management plan and
rehabilitation assisting man power
• Increasing human resources for rehabilitation 5. Mental Poor follow up/lack Improve coordination at
Health Care of coordination different level, teaching
• Expanding and decentralizing service delivery patient and caregiver skills for
System
• Increasing the use and affordability of technology and home based care
assistive devices Poor availability Improve training programs for
• Expanding research programs (Table-6: Barrier’s in of geriatric mental geriatric mental health care
Rehabilitation and Bridges to them) services services in form of skilled and
semiskilled man power
Poor financial Effective policy making to
13. Summary: resources improve budget allocation
The basic objective of rehabilitation is to restore the Poor research Promote research activities at
physical, social and psychological potential to a level, so all level- primordial prevention
to tertiary prevention.
that an individual can independently function and carry
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on an independent life. Rehabilitation should be aimed at
primordial level (promotion of healthy ageing), primary
level (universal, selective and indicative), secondary (early
diagnosis and management) and tertiary- preventing
disability and return to normalcy, to achieve maximum level
of restoration through different interventions. These may
involve training in vocational methods to suit working with
residual disability. To summaries:
• Ageing is inevitable and inescapable. Foresight and
planning can lead to healthy ageing.
• Rehabilitation should be initiated early, in health and in
illness.
• It is a long, dynamic and active process.
• Multidisciplinary approach is the appropriate way of
rehabilitation.
• Instituting measures of rehabilitation are important for
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Tiwari and Sonal: Rehabilitation needs of Elderly
better prognosis and life quality.
• Intervention is required for all conditions; however it
should be tailored to fit each individual.
• Ultimate goal should be to provide dignified life to
elderly.
• Need to change attitude of people towards mental
illness.
• Health staff needs to be trained and sensitized to needs
of elderly in health or in mental illness.
• Need to conduct outreach health programs to detect
early those individuals in need of rehabilitation.
• Data to support these recommendations is scarce. Need
medical research for evidence based practice.
“Crutches should not be made of woods but of carer’s/therapist’s
tolerance or patience”
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Neuropsychological Rehabilitation: theory and practice (ed) Wilson BA In

Table-7: General physiotherapy instructions for average Press:Swets & Zeitlinger. Available at Http://Members.Aol.Com/Morrisff/
Indian elderly Clare.Html
5. Clyburn LD, Stones MJ, Hadjistavropoulos T et al. Predicting Caregiver
1. Every morning-Breathing exercises of 10
Burden and Depression in Alzheimer’s Disease Gerontol B Psychol Sci
minutes Soc Sci. 2000 Jan;55(1 ):S2-13(283)
2. Self monitored whole body exercise of 10 6. Dean M. A law that would care for the carers. Lancet 1995; 345(8957):
minute duration(morning and evening) 1101 Department of Health and Human Services, elder care locator
3. Resisted exercise for week muscles of 5 minute (07/06/2005). Retrieved on 6thSeptember 2006 http://www.eldercare.gov/
duration three times daily eldercare/Public/resources/fact_sheets/respite care.asp
7. Donaldson C, Burns A. Burden of Alzheimer’s Disease: Helping the Patient
4. Neck and back strengthening exercises
and Caregiver Geriatric Psychiatry and Neurology. 1999; 12(1 ):21 -8
5. Pelvic floor strengthening exercises (Kegel’s) 8. Doolittle M, Bray J, Rosenbaum EH. Relaxation, Self-Care and Activities of
6. Abdomen strengthening exercises of 10 minute Daily Living. May, 1, 1999. Available at http//www.cancersupportivecare.
duration com/selfcare.html. Retrieved September 6th 2006 Encyclopedia of
7. Gait Training of 20 minutes twice daily Mental Disorders: Cognitive retraining, 2006. Available at http://
www.minddisorders.com/Br-Del/Cognitive-retraining.html
8. Joint exercises as advised by physiotherapist 9. Fillenbaum, G. Activities of Daily Living. In Maddox GL (ed.) The
9. Laughing exercise to increase lung capacity Encyclopedia of Aging. New York: Springer; 1987: pp.3-4.
10. Gelder M, Mayou, R, Cowen P (eds.) 2001. Psychiatry of the
elderly. In Shorter Oxford textbook of Psychiatry(4m ed). Oxford university
press, Oxford.
Table-8: Standard Dietary regimen for ref. Indian 11. Gormley N.The role of dementia training programs in reducing care giver
Elderly(Male) burden. Psychiatric bulletin2000,24,41-42
12. Gravis - Graham Vikas Vigyan Samiti (2004) retrieved September, 5, 2006
Age 70 from the world wide webhttp://www.gravis.org. in’elderly.htm
Sex male 13. Hinchliffe AC, Hyman I L, Blizard B et al. Behavioral complications
Body weight 60 kgs of dementia - can they be treated?International Journal of Geriatric
Physical activity Sedentary Psychiatry 1995; 10, 839-847.
14. Hutchinson SG, Tarrant J, Severs MR. An inpatient bed for acute nursing
Socioeconomic status Middle income group home admissions. AgeAgeing.1998 Mar; 27(2):95-8.
Food habits Vegetarian 15. Kasuya RT, Polgar-Bailey P, Takeuchi R. Caregiver burden and burnout: a
Recommended dietary allowance guide for primary carephysicians. Postgraduate Medicine 2000;108(7):119-23
16. Kennell D, Alecxih L, Erickson P et al The Estimated Costs of a Proposed
Energy 1976 kcal
Home Care Program: final report to the Commonwealth Fund Commission
Protein 60g on Elderly People Living Alone, May 22,1989
17. Kramer AF. Fitness Training and the Brain: From Molecules to Minds:
Calcium 400mg
Session 2028 - Invited Symposium: Optimal Aging and Cognition -
Diet chart Moderators of Cognitive Change and Decline at APA 2006
18. Larkin M. Reality Orientation, 1994. Available at: http://www.zarcrom.
Early morning One cup tea+2-3 biscuits com/users/alzheimers/t-02. html.Retrieved 6th September 2006
Breakfast Dalia/bread butter/boiled egg or 50 gm 19.a. National Institute of Social Defense, Ministry of Social Justice and
panneer Empowerment, Govt Of India(2005, March, 17) retrieved September, 5,
2006 from the world wide web http://nice.nisd.gov.in/publications.php
19.b. http://www.censusindia.gov.in/2011-Common/CensusData2011
20Proctor R, Burns A, Powell HS, et al. Behavioral management in nursing
APPENDIX and residential homes: arandomized controlled trial. Lancet. 1999; 3;
354(9172):26-9.
21. Rao VA. Family jointness, family and social integration among the elderly.
Important assessment scale in planning Rehabilitation Indian Journal of SocialPsychiatry. 1987; 3:81
are- 22. Rivlin, Alice M, Joshua M W et al. Caring for the Disabled Elderly: Who Will
• Katz Index of Activities of Daily Living Scale/EASI Pay? Washington, DC:The Brookings Institution. 1988
23. Sawhney, M. The Non Governmental Organization’s Commitment to the
I. Lawton Instrumental Activities of Daily Living Scale Elderly in India. In: LiebigPS, Rajan, SI (eds). An Aging India : Perspectives,
II. Diagnostic evaluation for functional impairment Prospects, and Policies New Delhi: Rawat; 2005
24. Shah B.Tradition and the future in India. Retrieved on 6tt5 September
III. Screening tests to identify impairments and factors 2006. http://www.islamset.com/healnews/aged/Bela_Shah.html
contributing to disability 25. Shapiro A, Taylor M. Effects of a Community-Based Early Intervention
Program on the SubjectiveWeil-Being, Institutionalization, and Mortality of
IV. Physiotherapy cum exercise regimen for average elderly Low-Income Elders. The Gerontologist2002; 42:334-341
is attached (Table-7). 26. Teri L, Logsdon RG, Uomoto. et al. Behavioral treatment of depression in
dementia patients: a controlledclinical trial. Journal of Gerontology. 1997;
V. Diet schedule for normal average elderly (Table-8). 52B, 159-166.
27. Wilcock G K, Bucks R S & Rockwood K (eds) (1999) Diagnosis and
REFERENCES Management of Dementia: A Manual for Memory Disorder Teams. Oxford:
Oxford University PressReardon M, Holmon R, DewhurstG. A survey of
domiciliary consultations in medicine for the elderly. Public Health 1995;
1. APA online. Public Policy office. (July 2003) Respite care significantly 109(3):187-90.
benefits caregivers and recipients of care :http://www.apa.org/ppo/issues/ 28. http://www.who.int/mental_health/en
respitefact03. html
2. Beers M, Jones TV et al. The Merck Manual of Geriatrics 3rd ed.2000.
Retrieved on 6* September2006 from world wide web http://www.merck. RESOURCES
com/mrkshared/mmg/sec3/ch28/ch28a.jsp
3. Borgenicht K, Carty E, Feigenbaum L Z. Community resources for frail A) List of journals related to geriatric mental heaLefth care
older patients., Care Management Journal 2005;6(2):80 i. Clinical Geriatrics
3. Cahn - Weiner DA, Malloy PF et al. Results of a Randomized Placebo- ii. Clinical Gerontologist
Controlled Study of Memory Training for Mildly Impaired Alzheimer’s iii. Geriatrics
Disease Patients. Applied Neuropsychohgy2003\10(4):215-23 iv. Geriatrics & Aging Online
4. Clare L. Rehabilitation for people with dementia. December, 17, 2001 In v. Gerontology

S424 Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018

[Downloaded free from http://www.indianjpsychiatry.org on Monday, March 19, 2018, IP: 117.249.137.147]

Tiwari and Sonal: Rehabilitation needs of Elderly

vi. Gerontology and Geriatrics 35) University Alzheimer Center, Case Western Reserve University
vii. Journal of Aging and Health D) LIST OF HOMES AND REHABILITATION CENTERS FOR SENIOR
viii. Journal of Applied Gerontology CITIZENS
ix. Journal of Gerontology 1) Directory of Old Age Homes in India, Research and Development Division,
x. Journal of Mental Health and Aging Help-Age India, 2016
xi. Psychology and Aging OLD AGE HOME DIRECTORY
xii. The Gerontologist Help Age India’s Directory of senior citizen’s guide (2016). Old Age Home
B) List of Evidence-based geriatric care books directory provides
1) Drug Prescribing for Older Adults: An Evidence Based Approach. Rosanne comprehensive information on 1012 old age homes in India. For copies of this
M. Leipzig, ed., directory, kindly sendRs.65/- as handling charges (By DD/MO only in
American College of Physicians, 2001. favor of Help Age India, New Delhi. Cheques from Delhi are acceptable).
2) Evidence Based Dementia Practice. Nawab Qizilbash et al., ed. Blackwell If you need the contact details of homes in any city or state, the same
Science Inc, 2001. would besent by post/e-mail free of cost. Address: Research & Strategic
3) Evidence-Based Rehabilitation: A Guide to Practice. Mary C. Law, ed. Slack, Development Department HelpAge
Inc., 2002. India C-14, Qutab Institutional Area, New Delhi 110016.
4) Geriatric medicine: An evidence-based approach. Christine K. Cassel, ed. Tel.No.:+91-11-1688955-59, 26966641, Fax : 91-11-26852916
4th ed. New York: Email: helpage@nde.vsnl.net.in or email to: anupama@helpageindia.org
Springer, 2003. info@helpageindia.org Website: http://www.helpageindia.org
5) Handbook of Pain Relief in Older Adults: An Evidence-Based Approach. F. 2) Website for the list of old age homes in different states http://www.seniorindian.
Michael Gloth Ed. com/index.htm
Humana Press, 2004. E) LIST OF THE VARIOUS ORGANIZATIONS WORKING FOR SENIOR
6) Practicing Evidence-based Geriatrics. Sharon Straus, David Sackett BMJ CITIZENS
Publishing Group, 1) Website for the list of NGOs working in India http://www.ngosindia.com
1999. F) SENIOR CITIZEN SECURITY CELL
C) List of the groups, associations, institutes & research centers working For example: The senior citizen security cell of Delhi.
in the field of The Senior Citizen Security Cell was set up on June 22nd, 2004 under the
geriatric mental health orders of CP/Delhi.
1) Indian Association of Geriatric Mental Health Objectives: The main objective of the cell is to coordinate, monitor and advise
2) Aging Clinical Research Center, Stanford University School of Medicine the area police regardinq the security and safety of the Senior Citizens.
3) Alzheimers.com Location: It is located on 1*’ Floor, Police Headquarters, M.S.O. Building, I. P.
4) Alzheimer Europe Estate, New r
5) Alzheimer’s Disease International Supervision: It is working under the supervision of Additional Commissioner of
6) Alzheimer Italia Police Crime, Lie
7) Alzheimer Society of Alberta Telephone Nos.: Direct: 23490233 (Tele-Fax) PHQ Exchange: 23490010/4336
8) Alzheimer Society, Canada
9) Alzheimer Society of Ottawa-Carleton
10) Alzheimer Society Romania This is an open access article distributed under the terms of the Creative
11) Alzheimer’s Association Australia Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
12) Alzheimer’s Association of Australia others to remix, tweak, and build upon the work non‑commercially, as long as the
13) Alzheimer’s Association of South Australia author is credited and the new creations are licensed under the identical terms.
14) Alzheimer’s Association of Tasmania
For reprints contact: reprints@medknow.com
15) Alzheimer’s Association Victoria, Australia
16) Alzheimer’s Association, New South Wales
17) Alzheimer’s Association, U.S. Access this article online
18) Alzheimer’s Disease Society, UK
Quick Response Code
19) Alzheimer Disease Research Center (ADRC)
20) Alzheimer’s Center, Stanford/VA Website:
21) Alzheimer Page, Washington University, St. Louis www.indianjpsychiatry.org
22) Alzheimer Research Forum
23) The Alzheimer Research Forum
24) Alzheimer Web
25) American Association for Geriatric Psychiatry DOI:
26) American Society on Aging 10.4103/0019-5545.224479
27) Association France Alzheimer
28) Alzheimer’s Disease Research at Mass. General Hospital
29) InsVtute tor Brain Aging and Dementia, University of California, Irvine
30) Institute of Gerontology, Wayne State University
31) LewyNet, Nottingham Medical School How to cite this article: Tiwari SC, Sonal A. Clinical Practice
32) Michigan Alzheimer’s Disease Research Center Guidelines for addressing the Rehabilitation Needs of Elderly
33) National Institute on Aging, U.S. in the Indian context. Indian J Psychiatry 2018;60:410-25.
34) National Ageing Research Institute, U.S.

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The Geropsychiatric Interview- Assessment and Diagnosis
Mathew Varghese, Ajit Bhalchandra Dahale
Geriatric Psychiatry Services, NIMHANS, Bangalore, Professor of Psychiatry, National Institute of Mental Health & Neuro
Sciences (NIMHANS), BANGALORE-560029, INDIA. mat.varg@yahoo.com
Other Expert participants: Arun V Marwale, D M Mathur
INTRODUCTION
The population of elderly persons is growing with
extraordinary rapidity. In the 2011 census of India the elderly
population comprised over 8 % of the total population,
making the estimated numbers of people above 60 years
age to over 100 million. Although the majority enjoys good
health, many older people suffer from multiple illnesses and
significant disability. They tend to exhibit great medical
complexity and vulnerability, have illnesses with atypical
and obscure presentations, suffer major cognitive, affective,
and functional problems, are especially vulnerable to
iatrogenic health problems, are often socially isolated and
poor and are at high risk for premature or inappropriate
institutionalization. Almost 45% of elderly suffer from some
chronic illness and many have two to three physical illnesses
together with a mental disorder. The prevalence of mental
disorders in the elderly ranges from 20-30% of which the
commonest are depression (10%) and dementia (3%). Hence it
is very important to recognise the magnitude of the problem
as India would have the second largest population of elders in
the world with a mental disorder. This fact would necessitate
that we anticipate and plan for geriatric care both in the
health system and in the families and community.
THE PSYCHIATRIC INTERVIEW OF THE
ELDERLY PATIENT
The bedrock of the diagnostic workup of an elderly patient
with a psychiatric disorder is the psychiatric interview. In
this chapter, we would detail the core components of the
psychiatric history taking, the mental status examination
and other bedside assessments. We would also assess other
domains important for the comprehensive management of
the patient like the medical, social, financial, environmental
areas. A brief note would also be given on the laboratory and
other investigations required to confirm a diagnosis. We will
also list out some structured interview schedules and rating
scales that are of value in the geropsychiatric assessment.
THE PSYCHIATRIC EVALUATION:
The clinician should first interview the patient together
with the family members to understand the presenting
© 2018 Indian Journal of Psychiatry | Published by Wolters Kluwer - Medknow
problem for which the consultation is made. Later it may
be necessary to interview the patient and family members
separately for information that is pertinent from the
respective persons. For example, it is better to interview
the patient separately when doing the neuropsychological
testing or when patient appears to be inhibited to discuss
his/her symptoms and to talk to the family separately while
enquiring about caregiver burden and distress. If the patient
has difficulty providing a reliable and adequate history,
the clinician should elicit the symptoms or problems that
the patient perceives as being most disabling and then fill
the gaps with data from the family members. Interview
techniques for patients with sensory [e.g hearing loss] or
cognitive impairment should be appropriately modified to
reduce inducing anxiety or irritability, for e.g. by talking
slowly and by explaining the nature and rationale of the
assessments.
The areas to focus in the history taking interview are given
below:
1. Presenting complaints and history of the current illness
2. Past psychiatric and medical history
3. Medication history
4. Family history and assessment
5. Personal history (including habits, nutrition, biological
functions and life style)
6. Premorbid personality
7. Mental Status Examination
1. The History of current illness
The review of symptoms is most valuable when considered
in the context of symptom presentation, including onset,
duration, severity and fluctuation, precipitating factors/life
events, prior efforts at addressing the symptoms and their
success, diurnal or seasonal variation, whether symptoms
cluster together, and whether they are ego-syntonic or ego-
dystonic. Open ended questioning should be attempted
initially followed by structured questioning. Defining a
1-month or 6-month window enables the patient to review
symptoms and events temporally—an approach not usually
taken by distressed elders, who tend to concentrate on
immediate sufferings.
Critical to the assessment of the current illness is an
assessment of function and change in function. The two
parameters that are most important are social functioning
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Varghese and Dahale: Geropsychiatric Interview
and activities of daily living (ADLs). Questions should be
asked about the social interaction of the older adult, such
as the frequency of his or her visits outside the home,
telephone calls, and visits from family and friends. The
clinician must ask about the patient’s ability to get around
(e.g., walk inside and outside the house), to perform certain
physical activities independently (e.g., bathe, dress, shave,
brush teeth, and select clothes), and to do instrumental
activities (e.g., cook, maintain a bank account, shop, and
drive). It is also important to assess how often the elder
actually engages in these activities.
The clinician must take care to avoid accepting the patient’s
explanation for a given problem or set of problems, yet
should acknowledge their perspective for developing
better rapport and understanding their explanatory model.
Statements such as “Most people slow down when they get
to be my age” can lull the clinician into complacency about
what may be a treatable psychiatric disorder. Also, the advent
of new and disturbing symptoms in an older adult between
office visits can exhaust the clinician’s patience, thereby
derailing pursuit of the problem. Distress over changes in
functioning, such as sexual functioning, may overwhelm
the older adult patient and, especially if the clinician is
perceived as unconcerned, may precipitate self-medication
or even a suicide attempt. The clinician should be watchful
regarding the discrepancies between report by patient and
family member/informant about the symptoms and should
assess for the motivations behind the same. Sometimes
multiple family members can also give conflicting accounts
of patient’s clinical picture, this should alert the clinician to
assess for the underlying motivations or family issues. This
would help the clinician plan the interventions for patient
and family in a better way.
2. Past Medical & Psychiatric History:
A past history of psychiatric disorder or details of past
episodes of illness should be documented together with
treatments given (medicines, psychological therapy, ECT
etc.), response to the treatments and side-effects if any.
Also, past or concurrent medical illnesses are important
in the causation, co-morbid interaction and for current
planning of the treatments. In patients with cognitive
decline it is prudent to check for occurrence of depressive
symptoms prior to the onset of cognitive symptoms.
Getting reliable and adequate information about the
past history may be a challenge due to poor memory
of the patient and inadequate information from the
accompanying family members. Nevertheless, it is useful
to explain to the family why this information is important
and to get past medical records that may be available
at home. Wherever it is possible to liaise, it would be
very useful to discuss with clinicians involved in patient’s
concurrent medical conditions for more comprehensive
care and avoiding confusion in management by the
different clinicians.
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3. Medication History:
All the medicines taken by the patient should be reviewed.
Though some of these medicines would have been
prescribed by another physician, many elders take over-the-
counter (OTC) medicines, alternative medicine treatments
or other medicines orally advised by some friend or family
member (usually for pain, digestion, bowel movements,
sleep or anxiety). A review must be made comparing the
prescription and the actual dosage that the elder is taking.
Very commonly there may be a discrepancy due to a problem
of forgetfulness or due to confusion because of too many
pills being prescribed. In addition to OTC or prescribed
medicines same elders may abuse alcohol, tobacco or other
drugs to counter their mental or physical symptoms. Hence
it is prudent to enquire about intake of these substances
which may cause harm or dependence.
4. Family History & Assessment:
It is useful to draw a 3-generation genogram of the family
of the patient. The genogram helps in many ways. In
addition to eliciting a history of similar or other mental
illnesses in the family we should also get details of the
family’s socioeconomic status, social supports, knowledge
and attitudes of the family members towards patient’s
condition, any family conflict or possibility of abuse of
patient or legal issues and details of possible caregivers of
the patient. In addition to a history of any mental disorder
or suicide, enquiry must also be made about significant
chronic medical illnesses like hypertension, diabetes
mellitus, stroke and other vascular risk factors. Interviewing
multiple family members, and preferably more than one
generation will help in improving accuracy.
It is very important for the geriatric psychiatrist to
engage with the family and to plan family interventions
as most treatment plans would need the cooperation and
involvement of family members. In addition to the family
support that is required to manage the patient, the family
is important for discussion of economic, social and legal
matters. The psychiatrist also needs to work with the family
to provide support and to relieve caregiver stress that is
commonly faced by caregivers as this has implications for
patient’s health and care as well.
5. Personal History:
A developmental life cycle perspective could be used to
get relevant details of the person from the time of birth.
The patient’s performance in school and college and the
occupational history about his past jobs and employment
history would highlight his functional ability in the past.
The age and circumstances of retirement will inform of
his attitude to work and retirement. Part or full-time jobs
held after retirement contribute to income and function.
Information about patient’s cultural, spiritual life and values
would be helpful in understanding the patient better and
planning the management. The nutrition history should give
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the type, quantity, and frequency of food eaten, including
the number of hot meals per week. Any special diets (eg.
low salt, low carbohydrate) or self-prescribed fad diets are
noted. The intake of alcohol, dietary fibre, and prescribed
or over-the-counter vitamins is recorded. The amount of
money the patient must spend on food and the accessibility
of food stores are important issues. Lack of suitable kitchen
facilities may prevent a patient from preparing meals. The
patient’s ability to eat (chewing, swallowing) is assessed.
It may be impaired by xerostomia (dry mouth), which is
common in the elderly. Decreased taste or smell may reduce
the pleasure of eating, so the patient may eat less. Patients
with decreased vision, arthritis, immobility, or tremors
may have difficulty preparing meals and may injure or burn
themselves when cooking. Patients who are worried about
urinary incontinence may reduce their fluid intake, which
may also lead to poor food intake.
THE MENTAL STATUS EXAMINATION:
The mental status examination of the elderly psychiatric
patient is crucial to the psychiatric diagnosis and clues to
many of these signs would be evident from a thorough
history-taking interview. The MSE may be evaluated on the
standard format used which covers the following areas:
1. General appearance & behavior (including psychomotor
activity)
2. Language and thought disorders
3. Mood
4. Perception
5. Cognitive functions- focusing on orientation, attention,
concentration, memory, intelligence
6. Judgement and insight
1. The general appearance of the patient, his grooming and
dressing would give an indication of how the person is able
to take care of themselves. In patients who are depressed,
demented or have psychotic symptoms the appearance
of the patient may give clues to the diagnosis. The facial
expression of the patient and the rapport that is possible
with the examiner would give an indication of whether
the patient is going through a psychotic or less serious
illness. The associated bodily movements and posture
of the patient would give further clues to the underlying
psychopathology. The psychomotor activity (whether
increased or retarded), general agitation and fidgetiness,
aimless pacing or distractibility of the patient would give
valuable clues as to whether there is depression, mania,
psychoses, delirium, dementia or generalized anxiety.
2. Language and thought disturbances: Disturbances
in thought content and stream are the most common
disturbances in persons with depression, psychoses and
sometimes with dementia. It is quite common for elder
depressed patients to have negative cognitions like
worthlessness, pessimism, hypochondriacal preoccupation
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or nihilism. Patients with psychoses or dementia may have
delusions of persecution, somatic delusions or of family
members stealing their personal belongings. Patients who
have anxiety and depression are likely to have worry or
preoccupation and tend to be repetitive in their thinking.
Sometimes the repetitive speech may be as a result of
perseveration, confabulation or other speech disorders seen
in organic disorders. The speech may become irrelevant or
incoherent with seeming disorders in associations or form.
Difficulty with respect to language may be the initial feature
in patients with dementia. Also, patients with stroke can
have aphasia or slurring of speech.
It is very important to not miss asking for and assessing
suicidal ideas. Though thoughts of death are common in late
life, elders do not readily express ideas of suicide. Hence
it is prudent to gently and specifically ask about ideas of
life not worth living, a wish to die or for specific plans or
even attempts. The threat of suicide is very high in the
elder population and many psychiatrists have suddenly lost
patients to suicide when they least expected it. As the risk is
very high it is necessary to assess if the implements [methods]
required for DSH are readily available to the patient.
3. Mood and Affect can be assessed by observing the patient
during the interview, getting their subjective report of
emotions that they experience and by assessing the stream
and content of their thoughts. It must be remembered that
the older adults’ repertoire of emotions may be constricted
and they may not exhibit the degree of sadness as younger
persons would. On the contrary, they may exhibit apathy
instead of anxiety or sadness. Labile affect can be noted in
patients suffering with dementia.
4. Perceptual disorders in the elderly quite commonly can
occur in all the five realms. Though auditory and visual
hallucinations or illusions are very common, it is also
common to see tactile, olfactory and gustatory sensations
especially when there is an organic condition or psychoses.
Patients with depression may also experience bad taste and
odors like that of putrefaction.
5. Cognitive functions and Memory are most accurately
assessed by formal psychological testing. However, the
psychiatric interview of the older adult must include a
reasonable bedside assessment of cognitive functions.
Cognitive functions should be assessed in the sequence
of first testing for orientation, moving on to attention
and concentration and then memory and other higher
functions like intelligence, abstraction and judgement. This
sequence should be followed as testing of memory and
other higher functions would require an intact attention,
concentration and orientation. Very commonly a disorder
of attention, concentration, orientation, or lack of interest
due to a psychiatric illness (depression or psychoses) may
be mistaken for dementia if not tested properly.
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Attention and concentration is tested by the digit span test
(digit forward and backward). In illiterate elders, we could
use days of week forward and backward or the 20-1 test.
Serial subtraction (100-7 or 40-3) is a test for concentration
and immediate memory and intelligence. Orientation can
be very simply checked by asking the patient’s awareness to
the time (time of day, day, date, month, etc), place (where,
town, address etc) and person (self, relatives, bystanders,
etc).
Memory is tested in the domains of immediate, recent
and remote memory. Testing of memory is based on
three essential processes of registration, retention and
recall. Memory is tested by asking the subject to learn and
memorize 3 or 5 objects and asking them to recall after a
few minutes after doing other tests. Asking the person to
recall an address with five different components is also an
accepted test for recent memory. Remote memory can be
tested by asking the subject to recall important local events
in the past. This may take the form of information required
for general information like the name of a political leader,
date of independence or time of festivals. It is not very
accurate to ask for details of meals that were eaten or events
in the past day though sequencing of events in the past few
days may be an indication of temporal spatial dysfunction
Memory which is autobiographical is lost last and so may be
used to test subjects who are moderately demented.
Registration is usually not impaired except in patients with
a moderate to severe dementia. However, retention can be
impaired by both psychic distress and brain dysfunction. For
example, lack of retention will be evident if unimportant
data like asking the patient to remember 3 objects for 5
minutes will frequently score a deficit if the patient has
little motivation to do the task.
6. Judgement, abstraction and Insight:
Abstract thinking is tested by asking the subject to give
the meaning and usage context of a common proverb.
Alternately for illiterate elders we could use the similarities
and differences test. Judgement and comprehension may
be tested by asking the patient to say what he would do in
certain situations (like the letter test, the fire in house test,
or what to do when it rains).
Insight is tested by asking the person why he has come for
consultation or whether he thinks he has an illness and the
explanation of the illness. Patients with depression, anxiety
or other milder forms of illness or mild cognitive impairment
would have insight while subjects with dementia, florid
psychosis or delirium would have absent insight.
Qualities of a geriatric psychiatrist & tips for effective
communication:
Most elders are just anxious and tired when they come to a
clinic and may have visual or hearing impairment that may
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cause confusion or poor performance in a test situation.
Older adults require a lot of patience and compassion from
the examiner and the examiner must address the elder in a
respectful and concerned manner. It is important to speak
slowly and clearly and repeat instructions (as some may
have hearing or other impairments). In addition to verbal
communication, non-verbal communication like being close
to the patient, touch or helping the elder about in the clinic,
would encourage cooperation of the elder for the detailed
and tedious examination that is involved.
The geriatric psychiatrist must have a sense of humour,
patience, a willingness to listen and explore possibilities
and not jump to conclusions and like older people. Working
with families is a key part of geriatric work. The person
must also believe that geriatric patients with psychiatric
issues do in fact get better and can lead a more fulfilling
and enjoyable life. An interest in psychiatry, medicine
and neurology is helpful and the person must have an
understanding of the many complex biopsychosocial factors
influencing psychiatric problems in an older person.
THE COMPREHENSIVE GERIATRIC
ASSESSMENT
As the elderly patient has multiple health problems that may
exist together, it is necessary to thoroughly evaluate these
problems that would have a bearing on comprehensive
management. Accordingly, in addition to the psychiatric
evaluation, many geriatricians recommend a Comprehensive
Geriatric Evaluation. This is a process of multidisciplinary
evaluation in which the multiple problems of older persons
are evaluated, and the resources and strengths of the
person are catalogued, the need for services assessed, and
a coordinated care plan is developed to focus interventions
on the person’s problems.
The goals of comprehensive geropsychiatric assessment
are:
(1) To improve diagnostic accuracy,
(2) To guide the selection of interventions to restore or
preserve health,
(3) To recommend an optimal environment for care,
(4) To predict outcomes, and
(5) To monitor clinical change over time
The setting: Structured Comprehensive geriatric assessment
may be done in many institutional settings, including acute
care, psychiatric, or rehabilitation hospitals and nursing
homes, and in ambulatory settings, including outpatient
or freestanding clinics, the offices of psychiatrists and
primary care physicians, or in the patient’s home. It has
often been applied to elderly persons at critical transition
points in their lives, including actual or threatened decline
in health and functional status, impending change in living
environment, bereavement, or other unusual stress
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Process: Comprehensive geropsychiatric assessment
is initiated by a referral from one of many sources. In
addition to the patient the process often includes family
members and other important persons in the individual’s
environment. It is conducted by a core team that consists
at a minimum, of a psychiatrist, nurse, and social worker,
each with special expertise in caring for older people. The
specific activities and contributions of each team member
may vary considerably, and flexibility in roles may facilitate
the assessment process.
The assessment begins with a case-finding approach that
utilizes screening instruments and techniques. Based
on these initial findings, a more detailed assessment is
frequently undertaken. This in-depth assessment often
requires the participation of many other professions. These
may include audiology, clinical psychology, dentistry,
nutrition, occupational therapy, optometry, pharmacy,
physical therapy, speech pathology, and the clergy.
Support from other medical disciplines, such as neurology,
ophthalmology, orthopaedics, physiotherapy, surgery, and
urology, is commonly needed. Self-rating scales completed
by the patient or caregivers may provide some aspects of
geropsychiatric assessment. Such information may lead to
different insights than those obtained through external
assessment performed by one member of the health care
team.
Comprehensive Geriatric Assessment [Reuben,2003]
comprises of the following components:
1. Physical health
2. Mental health
3. Functional Status
4. Social and Economic Status
5. Environmental characteristics
1. Physical Health: A careful history is obtained from
the patient and others with significant knowledge of
the patient. Special attention is directed to the use of
prescription and non-prescription medications and clues
to the presence of malnutrition, falling, incontinence,
and immobility. Data is gathered on smoking, exercise,
alcohol use, immunization status and sexual function. Also
important is information regarding the patient’s personal
strengths, values, perceived quality of life, acceptability
of interventions, and expected outcomes from his or her
health care.
The geriatric physical examination is performed with
emphasis on identification of specific diseases or conditions
for which curative, restorative, palliative, or preventive
treatment may be available. Special attention is directed
toward visual or hearing impairment, nutritional status,
and conditions that may contribute to falling or difficulty in
ambulation. Laboratory tests and other diagnostic studies
are obtained as indicated.
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The geriatric exam starts as soon as the patient is first seen
(observations are made about the patient’s appearance,
speech, ability to move around, etc.) and continues after
the formal exam is completed (i.e. does the patient have
problems with dressing himself/herself, finding the way
back to the car). Elderly patients may require additional
time to undress and transfer to the examining table for
the physical examination; they should not be rushed. The
examining table is adjusted to a height that the patient
can easily access; a footstool facilitates mounting. The
patient must not be left alone on the table. Portions of the
examination may be more comfortable if the patient sits in
a chair. The patient may want a relative or aide in the room
during the examination. Preliminary assessment of the
patient’s functioning can be made by observing personal
hygiene. The patient’s general appearance is described
(eg. comfortable, restless, malnourished, inattentive, pale,
dyspnoeic, cyanotic). If the patient is examined at bedside,
use of a water mattress, a sheepskin, bedside rails (partial
or full), restraints, a urinary catheter, or an adult diaper is
noted. During measurement of height and weight, patients
with balance problems may need to grasp grab bars placed
near or on the scale. When the temperature is recorded,
hypothermia can be missed if the thermometer does not
measure low temperatures. The absence of fever does not
exclude infection. The pulse and blood pressure (BP) are
checked in both arms. The pulse is taken for 60 seconds and
any irregularity noted. Because many factors can alter BP,
several measurements are taken under resting conditions.
As per the complaints of the patient examinations of
other systems like respiratory, GIT, Skin, Eyes, Ears, Nose,
Oropharyngeal, Neck/Thyroid, Lymphatic, Breasts, Heart,
Peripheral Vascular, Abdomen, Musculoskeletal & Pelvic/
Rectal may be carried out.
The neurological examination for an elderly patient, similar
to that for any adult, assesses cranial nerves, motor function
and sensory function. However, non-neurological disorders
that are common among the elderly may complicate the
neurological examination. For example, diminished sight
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and hearing may impede the assessment of cranial nerves,
and peri arthritis of the shoulder due to hemiplegia may
interfere with the assessment of motor function.
Signs detected during the examination must be considered
in light of the patient’s age, history, and other findings.
Symmetric findings unaccompanied by functional loss,
other neurological signs, and complaints may be a result
of aging. The physician must decide whether these findings
justify a detailed evaluation for a neurological lesion.
Patients should be re-evaluated periodically for functional
changes, asymmetry, or new complaints. Normal age-related
changes seen on neuro exam are decreased lower extremity
vibratory sensation, diminished knee jerk, diminished or
absent ankle jerk. Look for cortical release signs such as
grasp, palmomental, glabellar, and snout reflexes. Focused
on looking for neurological deficits that may be a sign of
neurological disease (CVA, Parkinson’s, etc). Difficulty may
be encountered in sensory exam if patient has altered
mental status or aphasia.
2. Mental Health: Cognitive, behavioural, and emotional
status is evaluated. Detection of dementia, delirium, and
depression is particularly important. A range of assessment
instruments is available for this purpose. For some
patients a detailed psychiatric interview, a neurobehavioral
consultation or comprehensive neuropsychological testing
is indicated. Details of the mental status examination have
already been discussed above.
3. Social and Economic Status: Evaluating the social support
network includes identifying present and potential caregivers
and assessing their competence, willingness to provide care
and acceptability to the older person. This information
may be obtained by questionnaires, structured interviews,
or other methods. The degree of caregiver stress and the
caregiver’s support network also are considered. Areas
of special importance to the individual, such as cultural,
ethnic, and spiritual values, are noted. The individual’s own
assessment of the quality of life is recorded. The clinician
evaluates the economic resources of the elderly person,
which often determine access to medical and personal care
and influence options for living arrangements
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4. Functional Status: There are several components to a
comprehensive assessment of an older person’s ability to
function. Physical functioning is usually measured by the
ability to accomplish basic activities of daily living (ADL)
including eating, bathing, toileting and dressing. Other
components of functional well-being are behavioural and
social activities that require a higher level of cognition
and judgment than physical activities. These instrumental
activities of daily living (IADL) include preparation of
meals, shopping, light housework, financial management,
medication management, use of transportation and use of
the telephone. Functional status (ADL and IADL) is probably
most accurately evaluated by direct observation of the
patient by family or health professionals in the home or
a simulated homelike environment. However, surprisingly
accurate information is also obtained by standardized
questionnaire or self-report.
5. Environmental Characteristics: Evaluating the patient’s
physical environment is essential. Home visits and
questionnaires are used to determine the safety, physical
barriers, and layout of the home as well as access to
services, such as shopping, pharmacy, transportation, and
recreation facilities
Home Visit Assessment: The Home Visit Assessment is an
essential part of the comprehensive geriatric assessment
most often done by social workers or public health nurses.
This assessment is important to understand the impact of
the patient’s environment on his problems, particularly
problems with risk of fall and functional disability. The
home visit adds to the functional assessment via direct
observation of a patient carrying out activities of daily living.
Assessing Competence: The level of Competence may be
required to be assessed in light of all the above to check
patients who have a cognitive dysfunction or are too
seriously ill with a psychotic illness that makes it difficult
for them to consent for treatment or for legal purposes.
Though Competency is a Legal term it is assessed for a task
within the specific framework as the person may vary in
giving consent for different tasks. The points that are to be
used for assessment are as follows:
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a) Give consent for medical treatment
b) Give power of attorney, draw and change a will
c) Consent by advance directives for research and withdrawal
of life support systems
Outcomes: Research has shown that through Comprehensive
Geriatric Assessment there was improvement in diagnostic
accuracy. The assessment also prolonged survival, reduced
annual medical care costs, reduced use of acute hospitalisation,
reduced nursing home use, increased use of health/social
services in the home, reduced medication use, improved
placement and improved cognition/functional status.
BASIC LABORATORY INVESTIGATIONS AND OTHER
STUDIES:
These laboratory investigations and other studies are
ordered after the geriatric history and physical examination
is completed and are used to detect diseases that are easily
missed in the history and physical such as anaemia, renal
impairment, hypothyroidism, vitamin B12 and vitamin D
deficiency and especially reversible aetiologies of cognitive
impairment (dementia).
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Neuropsychological Testing
Standardised neuropsychological batteries are available
in India to assess for the patient’s overall intellectual and
cognitive function normalized to the patient’s age and
baseline educational and sociocultural level. These tests are
important because we can often miss dementia completely
in patients subjected to the traditional medical interview,
particularly those that are well educated, socially adept, and
in denial of their cognitive problems. These tests should
be ordered for any geriatric patients that the clinician
suspects to have dementia even if the patient has a normal
screening (MMSE) score. The information from these tests
will then allow for proper characterization of the pattern of
cognitive deficits that will provide clues to the specific type
of dementia the patient is suffering from. Also, they would
help in periodic evaluation to look for progress over time
and the effect of medicines.
A standard neuropsychological battery available for India is
the Cognitive Screening Battery (Ganguli et al, 1996) and
the NIMHANS Neuropsychological Battery for the Elderly
(NNB-E). The Addenbrooke Cognitive Evaluation (ACE-R) has
also been standardised and translations are available for
many India languages.
Neuroimaging in Geriatric Psychiatry.
Neuroimaging techniques provide an opportunity to study
the structure and function of the brain in Elderly. Structural
imaging like CT Scan and MRI scan are useful tools though
information is limited
The CT scan is affordable and is good to detect large
structural lesions like haemorrhage (SDH) or infarcts, bony
abnormalities and calcified tumours, AV malformations,
and SOLs like Abscess, Tumours, inflammation and atrophy.
It is quick easy to perform, less costly and can be done
in presence of pacemakers and ferromagnetic bodies. Its
limitations are low resolution, poor visualization of the
posterior structures and isodense lesions (like cysts) and
white matter pathology.
The MRI Scan detects white matter abnormalities and has
excellent contrast between grey matter, white matter,
and CSF. It is the scan of choice as it can clearly delineate
tumours, abscess, haemorrhage, inflammation, and vascular
abnormalities like AV malformations. Only disadvantage is
its cost, time, and contraindications for metallic implants
like pacemakers and orthopaedic prosthesis. Advances in
radiotracer chemistry and instrumentation have increasingly
positioned neuroimaging methods as an interface between
basic and clinical neuroscience research.
The in vivo visualization of neurotransmitter metabolism,
transporters, and receptors with single photon emission
computed tomography (SPECT) and positron-emission
tomography (PET) has been made possible by advances in
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radiotracer development. At present many leading centres
are offering FDG- PET scans which may be used to study
the brain metabolism in patients who have depression, MCI
or dementia. Relevant to geriatric neuropsychiatry is the
development of radiotracers for the in vivo visualization
of amyloid and tau deposition in dementia and other
neurodegenerative disorders. The amyloid and tau CT/MRI
PET scans are yet available only for research purposes.
RATING SCALES AND STANDARDISED
INTERVIEWS:
Rating scales primarily used in research studies are useful
in clinical practice in assessment of the elderly to delineate
specific problems, documenting change, teaching and
communicating with colleagues and they can be useful in
insurance and medico legal purposes. There is a plethora
of scales that can be used but there is no single scale or
instrument to measure all pathology. In India there is also
the issue of using tests in the local language and hence
the issue of translation and validation in various languages
to maintain its reliability and validity at the same time
ensure that the items pertain to our culture and clinically
appropriate. Some of the widely used scales are listed
below.
COGNITIVE DYSFUNCTION AND DEMENTIA
SCHEDULES:
The Mini-Mental State Examination is a 30-item screening
instrument that assesses orientation, registration, attention
and calculation, recall, and language. It requires 5–10
minutes to administer. As per Western country norms
scores between 20 to 23 indicate mild dementia, between
10 to 19 indicate moderate dementia and below 10 indicate
severe dementia. However, the diagnosis should not be
solely based on the score but comprehensive assessment.
This instrument is perhaps the most frequently used
standardized screening instrument in clinical practice.
The MMSE has been adapted in India (as the Hindi Mental
State Examination-HMSE) and is used widely in many Indian
clinics and in research studies.
Clock drawing test
The clock drawing test takes only 2 minutes to administer
and reflects frontal and temporoparietal functioning
(Brodaty & Moore, 1997; Shulman et al, 1986). The main
advantages are its simplicity of administration and the non-
threatening nature of the task. The patient is asked to draw
a clock face marking the hours and then draw the hands to
indicate a particular time (e.g. 10 minutes past 11 o’clock).
Standardized methods of scoring have been described
with sensitivities of up to 86% and specificity of up to 96%
compared with diagnosis using the MMSE. This test is
particularly useful in the general practice setting but cannot
be used with illiterate population.
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Clinical Dementia Rating (CDR) scale is used as a global
measure of dementia (Hughes et al, 1982; Berg, 1984) and
is usually completed by a clinician in the setting of detailed
knowledge of the individual patient. Much of the information
will therefore already have been gathered, either as part of
normal clinical practice or as part of a research study. If a
specific interview is carried out, about 40 minutes is needed
to gather the relevant information. The full CDR interview
is available in many Indian languages. The CDR has become
one of the main methods by which the degree of dementia
is quantified into stages. Six domains are assessed: memory;
orientation; judgment and problem solving; community
affairs; home and hobbies; and personal care. Ratings are 0
for healthy people, 0.5 for questionable dementia (or MCI)
and 1,2 and 3 for mild, moderate and severe dementia as
defined in the CDR scale.
BEHAVIOURAL AND PSYCHOLOGICAL
SYMPTOMS
The Neuropsychiatric Inventory (NPI) evaluates a wider
range of psychopathology than comparable instruments
(Cummings et al, 1994). It may help distinguish between
different causes of dementia, records severity and frequency
separately, and takes 10 minutes to administer. The NPI
assesses ten domains: delusions; hallucinations; dysphoria;
anxiety; agitation/aggression; euphoria; disinhibition;
irritability/lability; apathy; and aberrant motor behaviour. A
screening strategy is used to cut down the length of time
the instrument takes to administer, but obviously it takes
longer if replies are positive. It is scored from 1 to 144 and
severity and frequency are independently assessed. The NPI
has been translated into many languages and it is now used
widely in drug trials.
The BEHAVE-AD (Reisberg et al, 1987) takes 20 minutes to
administer by a clinician and was designed particularly to be
useful in prospective studies of behavioural symptoms and in
pharmacological trials to document behavioural symptoms
in patients with Alzheimer’s disease. The BEHAVE-AD is the
original behaviour rating scale in Alzheimer’s disease. It is in
two parts: the first part concentrates on symptomatology,
and the second requires a global rating of the symptoms,
on a four-point scale of severity. The domains covered are
paranoid and delusional ideation; hallucinations; activity
disturbances; aggression; diurnal variation; mood; and
anxieties and phobias.
Cornell Scale for Depression in Dementia:
The Cornell Scale (Alexopoulos et al, 1988) is specifically
for the assessment of depression in dementia and is
administered by a clinician. It takes 20 minutes with the
carer and 10 minutes with the patient. It differs from other
depression scales in the method of administration rather
than in analysis of any different symptom profile seen in
depression with dementia compared with depression
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alone (Purandare et al, 2001). The 19-item scale is rated
on a three-point score of ‘absent’, ‘mild or intermittent’
and ‘severe’ symptoms, with a note when the score is
unevaluable. A score of 8 or more suggests significant
depressive symptoms. It is the best scale available to assess
mood in the presence of cognitive impairment.
ACTIVITIES OF DAILY LIVING:
Bristol Activities of Daily Living Scale was designed
specifically for use in patients with dementia (Bucks et al,
1996). The scale assesses 20 daily living abilities.
There are 2 scales available and standardised in India for
functional assessment of the elder patient. The Everyday
Abilities Scale for India (EASI) (Fillenbaum et al, 1999) is
a 12-item scale that can be easily scored after the history
is gathered from the family. It has both components
of functionality in basic Activities of Daily Living (ADL)
and Instrumental Activities of Daily Living (IADL). The
Instrumental Activities of Daily Living Scale for Elderly
(IADL-E) (Mathuranath, 2005) was developed by using 11
IADL items that are commonly carried out by Indian elders.
The Scale is able to give a composite index of cognitive and
physical disability.
DEPRESSION RATING SCALES
1.Center for Epidemiologic Studies Depression Scale
(CES-D). The scale consists of ratings of 20 behaviors and
feelings, and the patient indicates how frequently each
was experienced over the past week (from no days to most
days).
2. The Geriatric Depression Scale (GDS) was developed
because the scales discussed earlier present problems for
older persons who have difficulty in selecting one of four
forced-response items. The 30-item GDS permits patients to
Indian Journal of Psychiatry Volume 60 (Supplement 3), February 2018
Varghese and Dahale: Geropsychiatric Interview
rate items as either present or absent; it includes questions
about symptoms such as cognitive complaints, self-image,
and losses. Items selected were thought to have relevance
to late-life depression.
3. Hamilton Rating Scale for Depression (Ham-D) is by far the
most commonly used clinician rated scale. The advantage of
having ratings based on clinical judgment has made the Ham-D
a popular instrument for rating outcome in clinical trials.
4. Montgomery-Åsberg Rating Scale for Depression. This scale
follows the pattern of the Ham-D and concentrates on 10
symptoms of depression; the clinician rates each symptom on
a scale of 0–6 (for a range of scores between 0 and 60).
OTHER MEASURES OF PSYCHIATRIC
SYMPTOMATOLOGY
Brief Psychiatric Rating Scale
The Brief Psychiatric Rating Scale (BPRS) takes about 20
minutes and is administered by a trained interviewer. The
BPRS is a 16-item, seven-point ordered category rating
scale, which has been developed through previous versions
(Overall & Gorham, 1962). The questions are completed in
2-3 minutes following the interview.
Cambridge Mental Disorders of the Elderly Examination &
Geriatric Mental State examination
The Cambridge Mental Disorders of the Elderly Examination
(CAMDEX) and the Geriatric Mental State Examination (GMS)
are semi structured instruments which are designed to do
a standardised psychiatric interview for the elderly. The
resulting information provides a formal diagnosis in many
diagnostic categories (eg. dementia, delirium, depression,
mania, paranoid disorder, schizophrenia, anxiety and other
neurotic disorders etc).
GERIATRIC PSYCHIATRIC DIAGNOSIS
The commonly accepted diagnostic categories would be
the DSM IV-TR or the ICD 10. The new classificatory system
of the DSM-5 is quite different as it lays emphasis on a
categorical/dimensional model. The organic disorders have
undergone major revisions and have been designated as the
Neurocognitive disorders.
However most elderly are not known to fit into the
diagnostic categories as they have multiple overlap of
symptoms. Hence geriatricians have suggested a syndromal
approach. The syndromal diagnosis enables a therapeutic
approach and emphasises the multiple presentations and
co morbid medical illnesses in the Elderly. Blazer (2003) has
identified 7 Syndromes as below:
1) Acute Confusion or Delirium is a transient organic
brain syndrome characterized by acute onset and global
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Varghese and Dahale: Geropsychiatric Interview
Figure 1: Geriatric Assessment Algorithm
impairment of cognitive function. In elderly at times
a Hypoactive delirium is seen with apathy. There are
biological, cognitive and environmental contributors
2) Memory Loss or the Dementia syndrome that is a
frequent but disabling syndrome. It has a sustained decline
in cognitive function with insidious onset
3) Insomnia is more frequent than in any age group. They
may be Primary or Secondary. Others are Sleep Apnoea and
Nocturnal Myoclonus
4) Anxiety which may be Primary as GAD, Panic disorder;
or Secondary to Organic disorders or co morbid with other
Psychiatric disorders
5) Suspiciousness specially when experiencing cognitive
impairment ranging from distrust, increased cautiousness
to paranoid delusions
6) Depression that is most disabling subjectively and can be grief,
depressed mood co morbid with dementia, major depression
or late life depression. Cognitive impairment and psychotic
symptoms may be present and a challenge in treatment.
7) Hypochondriasis is a common and frustrating somatoform
syndrome. Some organic finding may be present but
not explain the symptoms and the symptoms do reach
delusional proportions
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In making a diagnosis in geriatric psychiatry it is useful to
follow an algorithmic approach and use a decision tree for the
better diagnosis and plan of management as is shown below.
*At all levels organic component and addictive substances
should be kept in mind as a possible contributory factor.
Also, disorders mentioned at higher level can have
symptoms mentioned further below.
CONCLUSIONS
Accumulated evidence indicates with moderate-to-high
confidence that comprehensive geropsychiatric assessment
is effective when coupled with ongoing implementation of
the resulting care plan. The most consistently demonstrated
favourable outcomes of comprehensive geropsychiatric
assessment have been prolonged survival, reduced annual
medical care costs, and reduced use of acute hospitals and
nursing homes. Although the evidence allows for alternative
interpretation, it is probable that careful selection of patients
has contributed importantly to the ability to demonstrate
benefit from comprehensive geropsychiatric assessments.
In view of the seemingly indispensable role of monitoring
and implementation of the care plan in achieving desired
outcomes, ongoing health care should be linked systematically
to the process of comprehensive geropsychiatric assessment.
Thus, comprehensive assessment is an important pre-
requisite for planning psychiatric and medical care of
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Varghese and Dahale: Geropsychiatric Interview

this vulnerable population group. This will help in better
diagnosis, holistic management of the patients’ health
problems as well as building the doctor patient relationship
and work satisfaction for the doctors.
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SUGGESTED REFERENCES:
Access this article online
1. American Psychiatric Association: Diagnostic and Statistical Manual of
Quick Response Code
Mental Disorders, 5th Edition. Washington, DC, American Psychiatric
Website:
Association, 2013
2. Blazer DG: Geriatric Psychiatry. Textbook of Clinical Psychiatry. Ed. www.indianjpsychiatry.org
Robert Hales, Stuart Yudofsky Fourth Edition 2003
3. Burns, A. Lawlor, B. and Craig, S. Rating scales in old age psychiatry. Br.
J. Psychiatry, Feb 2002; 180:161-167
4. Devanand, DP. Psychiatric Assessment of the older patient. Comprehensive DOI:
textbook of Psychiatry. Ninth Edition Ed Benjamin Sadock and Virginia 10.4103/0019-5545.224471
Sadock 2009
5. Gallo, JJ, Fulmer, T, Paveza, GJ, and Reichel, W. Handbook of Geriatric
Assessment, 3rd edition. Gaithersburg, MD: Aspen Publishers; 2000: pp
101-148.
6. Mugdha E. Thakur, Dan G. Blazer, David C. Steffens (Eds). Clinical
Manual of Geriatric Psychiatry, American Psychiatric Association, 2014 How to cite this article: Varghese M, Dahale AB. The
7. Pinto C. “The Geropsychiatric Interview: Assessment and Diagnosis”. In: Geropsychiatric Interview- Assessment and Diagnosis. Indian J
Clinical Practice Guidelines for Geriatric Psychiatry, Indian Psychiatric Psychiatry 2018;60:301-11.
Society, 2007

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