TREATMENT OF

SCHIZOPHRENIA AND
MANAGEMENT OF DRUG SIDE
EFFECTS
Prepared by Dr. Abel Girma(PGY-1)
Moderator Dr. Ribka Birhanu(Assistant
professor of Psychiatry)
OUTLINE
• INTRODUCTION
• HISTORY OF SCHIZOPHRENIA MANAGMENT
• GENERAL MANAGEMENT PRINCIPLE
• ACUTE PHASE TREATMENT
• CONTINUTION PHASE TREATMENT
• MAINTENANCE PHASE TREATMENT
• PSYCHOSOCIAL TREATMENT
• ANTIPSYCHOTIC DRUGS SIDE EFFECT AND ITS
MANAGEMENT
• SUMMARY
Introduction
• Psychotic disorder characterized by disturbances in

• Thinking (cognition),
• Emotional responsiveness, and
• Behavior,

• Ranked by the WHO as one of the top ten illnesses

contributing to the global burden of disease.
Introduction cont’d
Introduction cont’d
History of schizophrenia treatment
During the late 19th and early 20th centuries,

• Hydrotherapy
• Sleep treatment
• Prefrontal lobotomy
• Insulin coma
• Convulsive therapy
• Chlorpromazine -1952s
• Clozapine –approved in 1990
Clinical Management of Schizophrenia
• Divided in to 3 phases

1. Acute Phase
2. Stabilization Phase
3. Stable Phase(Maintenance treatment)
ACUTE PHASE

 Characterized by psychotic symptoms requiring immediate clinical

attention during

Psychotic relapse or
First episode psychosis

 Treatment focuses on alleviating the most severe psychotic symptoms.

 Usually last from 4 to 8 weeks.
The Goals of Acute Phase treatment are

1. To ensure patient safety

2. To perform complete Physical and Psychiatric assessment
3. To provide prompt treatment of Psychotic symptoms
4. To establish Therapeutic alliance with the patient and their family

Acute phase treatment may involve psychiatric hospitalization if

patient safety or compliance cannot be ensured in a less
restrictive setting
 PRE-TREATMENT ASSESSMENT

• Physical examination with neurological examination ,

• A mental status examination,
• BMI & FBS
• Laboratory evaluation.
• ECG (and documentation of pretreatment QTc)
• Pregnancy test in women, and HIV test.
• Brain imaging in the setting of focal neurologic signs
• EEG if symptoms suggest seizure activity.
• Urine or serum toxicology screen for identification of intoxication/withdrawal
 Psychiatric assessment
Safety assessment
• Imminent danger to self or others may require acute
hospitalization.
• Elicit and document:
• History or presence of suicide attempt or suicidal ideation
• Prominent mood symptoms
• Command hallucinations, hopelessness, anxiety, EPS,
• Substance use disorders.
• History of aggression or violence during current or past
psychotic episodes
• Whenever possible elicit information from collateral
informants
 Pharmacotherapy
• Management of acute psychosis in schizophrenia will almost
always involve the use of an antipsychotic agent

• Frequently, treatment augmentation with benzodiazepines

can be helpful in controlling severely distressed patients

• If possible, administration of any medication should follow a

doctor-patient discussion of the risks, benefits, and alternative
treatments
 Use of antipsychotics in the acute
phase
• Initiated as soon as is clinically feasible
• The SGAs should be considered as first-line
medications
• Decreased risk of EPS
• Tardive dyskinesia
• Antipsychotics have similar efficacy in treating
positive symptoms
• Clozapine for patients with treatment-resistant
symptoms
• Cognitive, negative, and mood symptoms
• Comorbid conditions & associated symptoms
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Choosing among medications
• Patient’s past responses to treatment
• Medication’s side effect profile
• Patient’s preferences
• Intended route of administration
• Presence of comorbid medical conditions
• Potential interactions with other medications
• Dose should be both effective and not likely to cause side
effects

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Pharmacotherapy cont’d
• Oral administration is optimal to minimize patient
distress
• IM agents may be necessary to reduce acute
agitation and psychosis in non compliant patients
• Commonly used agents include:
• Olanzapine 5-10mg IM or Ziprasidone 20mg IM.
• Haloperidol 5-10mg IM (consider with benztropine 1-2mg)
Adjunctive medications in the
treatment of acute psychosis

Benzodiazepines
• Are not indicated as monotherapy
• Commonly used in conjunction with antipsychotics
in treatment of acute anxiety, agitation, catatonia
• Benzodiazepines may be administered in oral and
parenteral form
• Lorazepam 1-2mg IM/po/IV or
• Diazepam 5-10mg IM/po/IV.
 Use of ECT in acute phase
• Severe psychotic symptoms that have not responded to
antipsychotics.
• If comorbid depressive symptoms are resistant to treat or
• if features such as suicidal ideation and behaviors .
• Prominent catatonic features that have not responded to
an acute trial of lorazepam
• Greatest therapeutic benefits appear to occur when ECT
is administered concomitantly with antipsychotics
• A trial of clozapine will generally be indicated before acute
treatment with ECT.
First-episode patients
• More sensitive to the therapeutic effects and side effects
• Should be started on lower dose of SGA.
• No differences between antipsychotic class in terms of efficacy
or discontinuation rates.
• More than 70% achieve remission within 3–4 months
• Medication should be continued for at least 2 weeks unless
there are significant tolerability issues
• If there is no response to medication after 4 weeks, despite
dose
optimization, a change in antipsychotic should be considered
• Where there is partial response, this should be reassessed after
8 weeks unless there are significant adverse events.
 Psychosocial interventions in the
acute phase
• Reducing over stimulating or stressful relationships,
environments, or life events
• Promoting relaxation or reduced arousal
• Simple, clear, coherent communications and
expectations
• Structured and predictable environment
• Low performance requirements
• Tolerant, non demanding, supportive relationships
• Psychoeducation of the patient and the family
• Best time to initiate a relationship with family members
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STABLIZATION PHASE
• In which acute symptoms have been controlled
• But patients remain at risk for relapse if

• treatment is interrupted or
• if exposed to stress.

• Treatment focuses on consolidating therapeutic gains, with similar treatments

as those used in the acute stage.
• This phase last as long as 6 months following recovery from
acute symptoms.
 Goal of Stabilization phase
1. Sustained symptom remission
2. Adherence to medication and therapy
appointments.
3. Minimization of stress.
4. Successful transition and continued support in the
community.
5. Establishment of a long-term treatment plan.
6. At each appointment, body weight, waist
circumference, pulse, and blood pressure should
be recorded to screen for early signs of metabolic
syndrome.
 Goal of Stabilization phase cont’d
7. Monitoring for common side-effects (EPS,
sedation).
8. Educate patient and family about the illness
and contributing factors to relapse, including
medication non adherence and substance
use.
9. Educate and engage patient in symptom
monitoring.
Stable phase
•Symptom remission or control is sustained
•Maintaining or improving level of functioning and quality of
life
•Psychosocial interventions as adjunctive treatment

Lower the relapse rates
•Decreasing antipsychotic doses to minimize side effects
•Weighed against the disadvantage of a greater risk of relapse
•Monitoring for adverse treatment effects continues
 Stable phase cont’d
• Reduction of relapse risk
 Relapse in the stable phase of illness is less than 30%
per year
 Without maintenance treatment
 60%–70% of patients relapse within 1 year
 Almost 90% relapse within 2 years
 It is recommended that first-episode patients continue
maintenance antipsychotics for no less than one to
two years
 Indefinite maintenance antipsychotic medication
 Multiple prior episodes or Two episodes within 5
Patients with treatment resistant
illness
• Little or no symptomatic response to multiple (at least
two) antipsychotic trials of an adequate duration (at
least 6 weeks) and dose (therapeutic range)
• May occur in about 10%–30% of patients
• Rule out factors influencing treatment response
 concomitant substance use,
 rapid medication metabolism,
 poor medication absorption,
 interactions with other medications, and
 other effects on drug metabolism(Smoking)
 Adherence issues
 possibility of another concomitant disorder should be
considered.
Treatment resistant illness cont’d
• Clozapine should be considered for patients whose schizophrenia has not
responded to two antipsychotics.
• Slow dose titration to minimize the risks of seizure, orthostatic hypotension,
and excessive sedation.
• starting dosage of 12.5 mg once or twice daily,
• Dosage can be increased by, at most,12.5-25mg/day to a target dosage of
300–450 mg/day every one to two days
• Subsequent dose increases, if needed, should be of 100 mg or less, once or
twice weekly.
• Efficacy is often seen at a dosage of 300–450 mg/day.
Treatment resistant illness cont’d
• Contraindications for treatment with clozapine
• Neutropenia= ANC <1500/microL
• Severe cardiac disease.
• Poorly controlled seizures
• Previous hypersensitivity to clozapine.
• Pretreatment assessment
• CBC, BMI, FBS,Lipid profile, ECG, Vital signs
Treatment resistant illness cont’d
• Monitoring for Clozapine treatment
• CBC
• Weekly during the first six months
• Every other week for the second six months
• Every four weeks after one year
• CVS
• Eosinophil count
• ESR/C-reactive protein
• Troponins
• Metabolic
• GI
Treatment resistant illness cont’d
• Side effects of Clozapine
Neutropenia/agranulocytosis
Myocarditis/cardiomyopathy
Pulmonary Embolism
Weight gain
Insulin resistance
Seizures
Clozapine-induced hyper salivation
Sedation
Constipation.
Treatment resistant illness cont’d
• Ultra treatment resistant schizophrenia
• Patients who have failed an adequate clozapine trial

• With adequate steady state plasma concentration(>350ng/mL), and adequate duration

of treatment(2 -3 weeks after a dose increase).
• Antipsychotic drug augmentation with
oECT
oTrans cranial magnetic stimulation
oAntidepressant drugs
oTopiramate
Psychosocial Treatment of Schizophrenia
• Integration of medical and psychosocial interventions are necessary and
complementary interventions to improve clinical symptoms, functional
outcome, and quality of life.
• Psychosocial interventions address many aspects of recovery, from reduction
of acute symptoms to improvement in functioning and general well-being.
• Patients should be supported in developing effective self-management skills
for improving their symptoms, functioning, and quality of life.
• The clinical team, the patient, and family members should develop shared
short term and long term goals for treatment and recovery.
• Patient and family preferences should be considered in the identification of
treatment goals and methods.
Psychosocial Treatment cont’d
• Family Intervention
Should be offered to all individuals diagnosed with schizophrenia who
are in close contact with or live with family members.
Should be considered a priority when there are persistent symptoms or
a high risk of relapse.
Family intervention should encompass
Communication skills
Problem solving
Psychoeducation
Psychosocial Treatment cont’d
• Cognitive-Behavioral Therapy for psychosis
Can be started during the acute phase or recovery phase,
For those experiencing persisting symptoms of psychosis, anxiety or depression.
Research indicates a 20-40% reduction in distress related to psychotic
symptoms
Includes patients monitoring the relationship between their thoughts, feelings,
behaviors, and symptoms;
Reevaluation of perceptions, beliefs, and thought processes
that contribute to symptoms;
Promotion of beneficial ways of coping with symptoms; reduction of stress; and
improvement of functioning.
Psychosocial Treatment cont’d
• Supported Employment Programs
• Offered to those who wish to find or return to work.
• Educational or occupational trainings for those unable to find work.
• Social Skills Training
• such as conversational skills, making friends, job interviews and
assertiveness.
• Life Skills Training
• practical aspects of living such as personal self-care, grooming and
hygiene, domestic skills, transportation, and managing money
• Patient Education
• about the nature of schizophrenia, as well as factors that contribute to
their onset, course, and treatment,
ANTIPSYCHOTIC DRUGS SIDE
EFFECTS AND MANAGEMENT
• Side effects might occur before clinical improvement.
• Affects patient’s interpretation of a drug’s effectiveness.
• Powerful predictor of drug reluctance.
• Warning patients about the potential side effects &
• Minimizing adverse effects is of paramount importance.
 EPS- acute dystonia, akathisia, parkinsonism.
 Constipation, dry mouth and blurred vision.
 Tachycardia, hypotension, QTc prolongation.
 Lethargy, hyperprolactinaemia, sexual and Menstrual problems.
 Metabolic- weight gain, Diabetes, Dyslipidemia
 S/e of clozapine.
Akathisia
• Greek word meaning ‘not to sit still’
• Most common form of EPS.
• Subjective component
• feeling of inner restlessness
• Objective component
• movements: such as pacing constantly;
• inability to stand, sit, or lie still, rocking
• More common with Haloperidol, Fluphenzaine
• uncommon with quetiapine, olanzapine, clozapine
Akathisia cont’d
• Risk factors
• High-dose and/or high-potency antipsychotics,
• Chronic use of antipsychotics,
• Rapid increase/sudden withdrawal of antipsychotics,
• Use of intramuscular depot preparations,
• History of organic brain disease (e.g. dementia,
alcoholism, HIV),
• History of previous akathisia,
• Concomitant use of predisposing drugs (e.g. lithium,
SSRIs)
Akathisia cont’d
• Acute akathisia occurs within hours to weeks of
starting antipsychotics or increasing the dose
• Chronic akathisa Akathisia that has persisted for
several months or so
• The reported rates of akathisia vary from 10%–
15% to as many as one third of patients treated
with antipsychotics.
Treatment
• Reduce the antipsychotic dose
• Change to another antipsychotic drug
• Propranolol 20–80 mg/day
• Benzodiazepines like Lorazepam
• Anticholinergics like Benzotropine
• 5HT antagonists, diphenhydramine
 Acute Dystonia
• Uncontrolled intermittent and sustained spasms
• Muscles of the head and the neck, leading to involuntary
movements.
• Experienced as the most frightening and painful side effect
• In 10% of patients on FGA
• In 2% of patients on SGA
• 10% occur during the first hours of drug treatment
• 90% occur within the first 3 days
Risk factors for dystonia
• Young age
• Male sex
• Neuroleptic naïve patients
• Large dosages of high-potency FGAs
• Cocaine use
• History of acute dystonic reaction
 Common types of dystonia
• Opisthotonos: a rigid contraction of the back muscles with
arching
• Retrocollis and torticollis of the neck
• Oculogyric crisis: a spasm in which an eye or both eyes are
turned upward
• Macroglossia and tongue protrusion: which can lead to
choking
• Laryngeal dystonias
• Rarely, dystonias of laryngeal or pharyngeal muscles can
lead to sudden death.
Treatment of dystonia
• Anticholinergic drugs given orally, IM or IV
• Benzotropine 1 to 2 mg
•  Diphenhydramine 50 mg
• Continue an oral anticholinergic medication to
prevent recurrence
• Switching to an antipsychotic with a low propensity
for EPS
• Botulin toxin
• Repetitive trans cranial magnetic stimulation (rTMS)
Acute dystonia cont’d
• Preventive measures
Adding an anticholinergic medications and benzodiazepines
Prophylactic anticholinergic for IM Haloperidol especially in
neuroleptic naive patients.
Clinical Monitoring.
 Drug-Induced Parkinsonism
• Experience all of the common motor symptoms of
idiopathic parkinsonism
• Rigidity
• Bradykinesia (decreased facial expression, flat
monotone voice, slow body movements, inability to
initiate movement)
• Shuffling gait
• Tremor
• Bradyphrenia (slowed thinking)
• Salivation
 Drug-Induced Parkinsonism
• During the first 5 to 30 days of treatment.
• Approximately 20% patients.
• First evidence may be a diminished arm swing or
decreased facial expressiveness.
• Risk factors
• Increasing age
• Female sex
• High dose
• History of parkinsonism
• Underlying basal ganglia damage (e.g., vascular insult)
 Drug-Induced Parkinsonism
• In its milder forms, may appear as a
• Decrease in spontaneous gestures
• Masked facial expression
• Apathy
• Unspontaneous speech
• Difficulty in initiating usual activities(akinesia)
• Mistaken for depression or negative symptoms of
schizophrenia in the absence of motor symptoms
• Can usually be diagnosed by examining for cog wheel
rigidity or
• Observing for a diminished arm swing when the patient
walks.
 Treatment of Drug-Induced parkinsonism
• Reduce the antipsychotic dose
• Change to an antipsychotic with lower propensity
• Anticholinergic antiparkinsonian medications
• Benzotropine at 1 to 2mg/day in divided doses
• gradually increase every three to four days to 6
or 8 mg/day
• Majority of patients don’t require long-term rx
• Amantadine is an alternative treatment
• 100 mg orally two to three times daily.
• Amantadine can cause hypotension and mild
agitation
 Monitoring
• Evaluate for EPS weekly until the medication dose has been
stable for at least two weeks.
• Twice weekly assessments should also follow any
significant dose increase.
• Once stabilized, the frequency of EPS assessment should
depend on
• Patient’s sensitivity to EPS
• EPS liability of their antipsychotic
 Tardive dyskinesia(TD)
• TD is a hyperkinetic movement disorder
• Delayed onset after prolonged use of dopamine receptor
blocking agents.
• Has been reported after exposure to any of the available
antipsychotic medications.
• Occurs at a rate of approximately 4%–8% per year in adult
patients treated with FGAs
• May appear as early as one to six months following
antipsychotic drug exposure.
Risk factors for TD
• First treatment after age 65
• Elderly women
• Affective disorder treated with dopamine receptor
antagonist
• High dosage of more potent antipsychotic medications
• Longer duration of treatment
• Presence of acute EPS
• Anticholinergic antiparkinson drugs
• Dementia
• Diabetes
Clinical features of TD
•  Symptoms involve the mouth, tongue, face, trunk, or
extremities.
• Oral, facial, and lingual dyskinesia occur in three fourth of TD
patients & may include
• Protruding and twisting movements of the tongue
• Pouting, puckering, or smacking movements of the lips
• Retraction of the corners of the mouth
• Bulging of the cheeks
• Chewing movements
• Blepharospasm
• Severe orofacial dyskinesia is disfiguring and may greatly
interfere with speech, eating, swallowing, or breathing
Clinical features of TD cont’d
• Dyskinesia of the limbs also occur, such as
• Twisting, spreading, and "piano-playing" finger movements
• Tapping foot movements
• Limb involvement is often more severe in younger individuals.
• Dyskinesia of the neck and trunk may include the following
• Retrocollis Torticollis
• Axial dystonia
• Shoulder shrugging
• Rocking and swaying movements
• Rotatory or thrusting hip movements
• Truncal dystonia can be extremely distressing and interfere with gait and
mobility
Clinical features of TD cont’d
• Seriously disabling TD is uncommon
• Affect walking, breathing, eating, and talking
• Movements are worse when under stress
• TD may be associated with neurocognitive deficits
• Takes months to years
• Approximately 50% of cases are reversible
• Early identification of TD in younger outpatient populations
is associated with remission in 50 to 90 percent of patients
 DDx. of TD
• Disorders of the basal ganglia
• Huntington disease
• Wilson disease
• Sydenham chorea
• Striatal hypercalcifications
• Hyperthyroidism
• Hypoparathyroidism
• Dyskinesia related to other drugs
• L-dopa, amphetamines, anticholinergic, anticonvulsants,
antidepressants
• Patients with schizophrenia before medications
The APA recommendations for preventing
and managing TD

1. Establishing objective evidence that antipsychotic medications are effective for an

individual
2. Utilizing the lowest effective dose of antipsychotic;
3. Prescribing cautiously with children, elderly patients, and patients with mood
disorders;
4. Examining patients on a regular basis for evidence of TD;
5. When TD is diagnosed, consider alternatives to the antipsychotic being used, and
also consider dosage reduction;
6. If the TD worsens, consider a number of options, including discontinuing the
antipsychotic or switching to a different drug.
Management of TD
• Prevention, Early detection, and Management of potentially reversible cases are
the cornerstones of modern treatment.
• Discontinuation of the offending drug
• Switching from a FGA to a SGA
• Use of benzodiazepines,
• Botulin toxin injections to specific muscle groups
• Reversible inhibitors of vesicular monoamine transporter 2 (VMAT2) drugs like
valbenazine or tetrabenazine
• Anticholinergics are usually ineffective or may even exacerbate TD
• Paradoxically, resuming treatment with antipsychotic drugs in some patients
with permanent and disabling or life-threatening TD that is treatment-resistant
 Management of TD
• Patients receiving FGAs for more than 6 months should
have regular and systematic evaluations for TD every 6
months.
• Abnormal Involuntary Movement Scale (AIMS)
• Consideration of the dangers of both the psychotic illness
and TD
• Involve the patient and his/her family
• Document in the patient’s medical record
• Most chronic schizophrenia: continuing the antipsychotic
• Lowest effective dosage
• Severe TD: trial of clozapine or other SGAs.
 Prevention
• The only certain method of prevention is to avoid
treatment with antipsychotic drugs and metoclopramide .

• Antipsychotic drugs, particularly for longer than three

months

• Metoclopramide should NOT be used continuously for

longer than 12 weeks.

• Inform patients of the risk of developing TD before treating

with antipsychotic drugs or metoclopramide
 Neuroleptic Malignant Syndrome
• Uncommon but a life threatening neurologic emergency
• Usually presents as muscular rigidity and progresses to elevated
temperature, fluctuating consciousness, and unstable vital signs.
• Its main clinical features include
• Changing levels of consciousness
• Initial sign in 82%
• Confusion, catatonic signs, mutism, coma
• Severe muscular rigidity
• Generalized, tremor, dystonia, opisthotonus, trismus, chorea,
other dyskinesias, sialorrhea, dysarthria, and dysphagia
• Hyperthermia
• In some study delay in 24 hrs.
• Autonomic instability
• Tachycardia, increased BP, tachypnea, diaphoresis
• The tetrad typically evolves over one to three days
• Each feature is present in 97 to 100 percent of patients
 NMS

• Symptoms are often associated with

• Elevations in CPK and aldolase
• Elevations in liver transaminases
• Leukocytosis
• Myoglobinemia
• Myoglobinuria
• Acute renal failure
• Early recognition of NMS has led to a substantially
decreased mortality rate.
 NMS
• Risk factors
• High-potency FGAs in high doses
• Recent or rapid dosage escalation
• Switch from one agent to another
• Parenteral administration
• 0.02-3% among patients taking neuroleptic agents
• Twice as common in men as in women
• More likely to be present in younger patients
• Mostly in a first two weeks of neuroleptic therapy
• Single dose or after Rx. with the same agent at the same dose
for many years
• Early diagnosis and treatment can be life-saving
Drugs that can cause NMS
• Neuroleptic agents • Antiemetic agents
• Aripiprazole • Domperidone
• Chlorpromazine • Droperidol
• Clozapine • Metoclopromide
• Fluphenazine • Prochlorperazine
• Haloperidol • Promethazine
• Olanzapine
• Paliperidone
• Perphenazine
• Quetiapine
• Risperidone
• Thioridazine
• Ziprasidone
 DDx. Of NMS • Unrelated disorders
• Related disorders
• Serotonin syndrome • CNS infections,
vasculitis
• SSRIs
• Hyperreflexia, myoclonus, ataxia • Systemic infections
• N, V, diarrhea • Seizures
• Less severe • Acute hydrocephalus
• Malignant hyperthermia • Acute spinal cord
• Rare genetic disorder injury
• Potent halogenated inhalational anesthetics • Tetanus
• Malignant catatonia • Thyrotoxicosis
• Behavioral prodrome of some weeks • Pheochromocytoma
• More positive phenomena
• Normal Lab. values
• Other drug-related syndromes
• Central anticholinergic syndrome
• Cocaine and other recreational drugs
 Management of NMS
• Stop causative agent
• Single most important treatment
• Psychotropic agents ( lithium, anticholinergic,
serotonergic)
• If discontinuation of dopaminergic therapy
• Supportive care
• Dehydration
• Electrolyte imbalance
• ARF, DVT, DIC
• Cardiac (Arrhythmias, MI, Cardiomyopathy)
• Respiratory failure
• Seizures
• Hepatic failure
• Sepsis
 Management of NMS
• Supportive and symptomatic treatment
• Treating EPS with antiparkinsonian medications
• Correcting fluid and electrolyte imbalances
• Treating fevers
• Managing cardiovascular complications such as hyper-or
hypotension
• Benzodiazepines- Lorazepam 1 to 2 mg IM or IV every four to six
hours. Diazepam is dosed as 10 mg IV every eight hours
• Dantrolene (Dantrium)
• Direct-acting skeletal muscle relaxant
• IV: 0.8 to 2.5 mg/kg every 6hours, Max. of 10 mg/kg daily
• Orally in dosages of 100 to 200 mg daily
• Continued for 10 days after NMS is controlled and then tapered
slowly.
 Management of NMS
• Bromocriptine
• Dopamine agonist
• Added at doses of 20-30 mg daily in QID
• Amantadine
• Dopaminergic and anticholinergic effects
• The course of treatment is commonly 5 to 10 days unless a long-
acting injectable agent has been used
• NMS is considered by some as an extreme form of EPS
• Its cause and biological risk factors are unknown
• Low-potency drugs may be preferable
• No data available to indicate whether clozapine or other serotonin–
dopamine antagonists are with lower risk
• ECT
 Prognosis
• Most episodes resolve within two weeks
• Six months with residual catatonia and motor signs
• Depot antipsychotic use
• Concomitant structural brain disease
• Most patients recover without neurologic sequelae
• Except severe hypoxia or grossly elevated temperatures for a long
duration
• Mortality in well-developed cases ranges from 20-30%
• Higher when depot forms used
• Disease severity
• Medical complications
• Organic brain disease
• Alcohol and drug addiction
 Restarting Neuroleptics
• May or may not have a recurrent NMS episode
• Reported relapse rates between 10 and 90 percent
• Risk factors for recurrence
• Early resumption of neuroleptic therapy
• Use of high potency
• Parenteral neuroleptics
• Concomitant use of lithium
• Wait at least two weeks before resuming therapy
• Longer if any clinical residua exist
• Use lower rather than higher potency agents.
• Start with low doses and titrate upward slowly.
• Avoid concomitant lithium
• Avoid dehydration
• Carefully monitor for symptoms of NMS
Weight gain
• Common feature of antipsychotic drug treatment.
• The molecular mechanisms for antipsychotic-induced Wt gain are not
fully known.
• Clozapine and olanzapine treatment caused the greatest weight gain in
different studies.
• Wt gain patterns seem to vary over the length of treatment.
• risperidone is associated with gains of 2–3 kg over 1 year period.
• olanzapine, mean weight gain ranged from 6.8 to 11.8 kg over 1 year.
• May also be more pronounced in antipsychotic‐ naive, genetically &
environmentally predisposed
 Weight gain, Treatment
• BMI: Weekly in the first 3 months, then every 6 month
• Treatment
• Switching drugs
• Behavioral programs(Exercise, Diet )
• Aripiprazole (5–15 mg/day) with
olanzapine/clozapine
• Metformin (500–2000 mg/day)

07/12/2023
Dyslipidemia
• Patients with schizophrenia are at increased risk for dyslipidemia, in part because of
poor diet and sedentary lifestyle.
• FGA
• Phenothiazine: increase triglycerides and LDL and decreases in HDL
• Haloperidol: minimal effect on lipid profile
• SGA
• Associated with elevations in triglyceride and total cholesterol levels,
• Olanzapine, clozapine, quetiapine
• Risperidone and aripiprazole have minimal effect.
• Treatment
• Fasting lipids at baseline, then every 3 months for a year, then annually
• Switching drugs, dietary advice, lifestyle changes, statins.
Diabetes and impaired glucose tolerance
• Patients with schizophrenia, even if drug naive, are 2–3 times
more likely to have type II diabetes than adults in the general
population
• Increased risk of diabetes in schizophrenia patients treated with
many atypical antipsychotics.
• Higher in patients taking clozapine or olanzapine than FGAs.
• Minimum of yearly testing for all patients(OGTT, HbA1C, FBS)
• Treatments
• Switching to a drug of low or minimal risk of diabetes
• Standard Hypoglycemic agents and Metformin.
Hyperprolactinaemia
•  FGAs, risperidone, and paliperidone can elevate plasma
prolactin.
• Quetiapine and Aripiprazole have a low likelihood of
increasing prolactin levels, and
• Aripiprazole can lower prolactin levels
• Signs and symptoms of Hyperprolactinaemia include
• Sexual dysfunction, menstrual disturbances, breast growth and
galactorrhoea , osteoporosis, breast cancer.
Hyperprolactinaemia cont’d
•Serum Prolactin levels should be measured if such symptoms
occur during treatment.
•Treatment
•Changing of the Antipsychotic.
•Metformin may reduce antipsychotic induced prolactin
elevations.
References
• Kaplan and Sadock’s Comprehensive Text Book of Psychiatry 10th
edition
• Kaplan and Sadock’s Synopsis of Psychiatry 11th edition
• APA Practice Guideline for Treatment of Patients with Schizophrenia,
2019, 3rd edition
• Canadian Treatment Guidelines on Psychosocial Treatment of
Schizophrenia in Adults 2017, Vol. 62(9) 617-623
• The Maudsley Prescribing Guidelines in Psychiatry 13th edition
• DSM-5
• Stahl essential psychopharmacology, the Prescriber’s guide 1st edition
• Up-to-date 21.6
•Thank You!