MANAGEMENT OF BIPOLAR DISORDER

MODERATOR: DR.RUPESH CHAUDHARY

BY-DR.ARDAAS SANDHU
 INTRODUCTION

 Bipolar and related disorders are episodic mood disorders defined by the occurrence of Manic, Mixed or
Hypomanic episodes or symptoms.

 These episodes typically alternate over the course of these disorders with Depressive episodes or periods of
depressive
symptoms.
(ICD 11 )
 Bipolar disorder is a chronic psychiatric disease often causing
disability and significant functional impairment.
 Bipolar disorder is a severe neuropsychiatric disorder affecting over 2.3 million adults, or
about one percent of this population.

 It frequently requires hospitalization and is associated with significant mortality due to

suicide, the rate of which is higher than that in the general population and other
psychiatric or medical patient populations
 DSM-5 AND ICD-11
DSM-5 ICD-11
Name Bipolar and related disorders Bipolar and related disorders

DISORDERS Bipolar 1 disorder Bipolar 1 disorder

Bipolar II disorder Bipolar II disorder
Cyclothymic Disorder Cyclothymic Disorder
Substance/Medication Induced Bipolar and Related Disorder Other specified Bipolar and
Bipolar and Related Disorder Due to Another Medical Condition Related Disorder
Other specified Bipolar and Related Disorder
1. Short duration hypomanic episodes (2-3 days ) and major depressive
episodes
2. Hypomanic episodes with insufficient symptoms and major depressive
episodes
3. Hypomanic episode without prioir major depressive episode
4. Short duration Cyclythymia (less than 24 months)
 DSM-5 ICD-11
SPECIFICATIONS Single episode of mania Occurrence of manic, mixed or
hypomanic episodes or symptoms
typically alternating with depressive
episodes or symptoms

Bipolar I- mania+/- depression Bipolar II Bipolar type I – one or more manic or

-hypomania and depression mixed episodes Bipolar type II- one or
more hypomanic and atleast one
depressive. There is no history of

Single manic episode enough to diagnose as Single episode is diagnosed as bipolar type I
bipolar disorder disorder

SYMPTOMS Abnormally and persistently elevated, Euphoria, irritability or expansiveness and by

expansive or irritable mood and increased goal increased activity and a subjective experience
directed activity or of increased energy

DURATION 1 week or less if hospitalization is necessary Last at least 1 week

3 or more of 7 other symptoms (4 if irritable Accompanied by other characteristic

mood) symptoms
 DSM-5 ICD-11

DEPRESSIVE SYMPTOMS 5 or more of 9 symptoms with at least one Depressed mood or loss of interest in
is either depressed mood or loss of daily activities
interest

DURATION 2 weeks 2 weeks

SEVERITY Severity based on no of criterion Severity determination is subjective

symptoms

No somatic syndrome No somatic syndrome

Psychotic features coded irrespective of Psychotic symptoms in moderate and

episode severity severe episodes
PREDICTORS OF BIPOLARITY

 Early age at onset

 Cyclothymia
 Postpartum Depression
 Rapid onset and offset
 Anergic Depression
 Baseline hyperthymic personality
 Recurrent depression Seasonality
 High density pedigree
 Hyperthymic temper
 Atypical symptoms
 Psychosis
 Depressive mixed state
 Anxious/agitated depression
 Brief duration of depressive episodes
 Irritability/anger attacks
 Antidepressant-induced mania
 Antidepressant-induced psychosis
 Acute nonresponse
 Tolerance
EVALUATION

 A complete medical and psychiatric history is the cornerstone of good practice.

 Areas for concentration during thephysical examination would be the endocrine system
and signs of alcohol or other substance abuse.

 As indicated, laboratory testing may include the thyroid stimulating hormone, a

toxicology screen, an electroencephalogram,or brain imaging.
SCALES USED FOR ASSESSMENT

 The scales used for assessment of bipolar depression include,

 The Hamilton Depression rating Scale (HAM-D)
 The Montgomery-Asberg Depression rating Scale (MADRS)
 Mood Disorder Questionnaire (MDQ),
 The Bipolar Depression Rating Scale
 Multidimensional Assessment of Thymic States (MAThyS) scale
 The ISBD Task Force has developed the FAST (Functioning Assessment Short Scale), for
bipolar disorder in particular.
COURSE

 Individuals with bipolar disorder most commonly suffer

relapses and remissions. Approximately 90 percent of them have had a psychiatric
hospitalization.
 During their lifetimes most have multiple admissions for a bipolar episode. Bipolar II
patients are more likely to present with depression than with hypomania or mania.
Comorbid substance abuse is common.
Guidelines for the management of patients with bipolar disorder

 Canadian Network for Mood and Anxiety Treatments (CANMAT)

 International Society for Bipolar Disorders (ISBD)
Lithium

 Lithium still remains the gold standard for the treatment of bipolar disorder
 Lithium has shown to be efficient in acute Bipolar Depression
 It is more effective than placebo in preventing relapse in bipolar depression patients. ,
lithium treatment reduces the overall risk of relapse by 40-60%
 It is found to be more effective in mania as compared to depressive phase of bipolar
illness
 Lithium is effective in preventing depressive and manic relapses
 Lithium is reported to possess anti- suicidal effectiveness
 A reduced risk of switching to mania is reported when treated with lithium
Formulations available

Dosage Forms
• Tablet 300 mg (slow release), 450 mg (controlled release)
• Capsule 150 mg, 300 mg, 600 mg
• Liquid 8 mEq/5 mL
Valproate

 Valproate is seen to be effective in treating acute bipolar depression

 It is less effective in depression when compared to use in manic episodes
 The response rate is seen to be about 30% in acute bipolar depression
 It is less effective than lithium in preventing depressive relapses
 Tablet [delayed release, as divalproex sodium (Depakote)] 125 mg, 250 mg, 500 mg
 • Tablet [extended release, as divalproex sodium (Depakote ER)] 250 mg, 500 mg
 • Capsule [sprinkle, as divalproex sodium (Depakote Sprinkle)] 125 mg
 • Capsule [as valproic acid (Depakene)] 250 mg
 • Injection [as sodium valproate (Depacon)] 100 mg/mL (5 mL)
 • Syrup [as sodium valproate (Depakene)] 250 mg/5mL (5 mL, 50 mL, 480 mL)
Lamotrigine

 Lamotrigine, the prototype class B mood stabiliser

 It is effective both as a treatment for acute bipolar depression and as prophylaxis against
further episodes
 Lamotrigine is found to be equally effective to lithium in the prophylaxis of bipolar
depression
 It is a good option for use in Pregnancy
Carbamazepine

 The overall response rate of carbamazepine in Bipolar Depression is about 55%

 It is significantly less effective than lithium in both acute as well as maintenance phase
of bipolar depression
 Is found to be more efficacious than lithium in presentations such as schizoaffective
illness, comorbid substance abuse or organicity
 • Tablet 100 mg chewable, 200 mg
 • Extended release tablet 100 mg, 200 mg, 400 mg
 • Extended release capsule 200 mg, 300 mg • Oral suspension 100 mg/5mL (450 mL)
QUETIAPINE

 Rapidly absorbed (food doesn’t interfere with absorption)

 Half life -7 hours so dosing is BD or TID
 It
has transient D2 blockade- faster dissociation which induces antipsychotic effects and
minimizes ADRs
 Least associated with EPS so used in Parkinson’s who develop drug induced psychosis.
 AVAILABLE as 25, 100, 200 mg tabs. (effective dose 50-400mg/day )
 Optimum dose is 500-750 mg ( started with 25 mg/day which is incremented by 25 or
50 mg twice or thrice daily)
OLANZAPINE

 85% absorption from GIT (food doesn’t interfere with its absorption)
 Reaches peak plasma concentration in 5 hours
 T-1/2 is 31 hours, so once-daily dose is sufficient.
 5HT:D2 blockade = 8:1
 Also has 5HT2A agonist activity - so used as anti anxiety as well.
 Dosages-2.5,5,7.5,10,15,20 mg tablets and a 10 mg injection form is also available for acute agitation.
( effective dose 2.5-20 mg /day)
 Ethanol increases olanzapine absorption by 25% whereas smokers require high doses for therapeutic
action.
MAINTAINENCE
BIPOLAR DEPRESSION

 Two models have been postulated related to represent the dichotomy between unipolar
and bipolar depression

 Bipolar depression and unipolar depression reflecting distinct disorders

 Bipolar depression and unipolar depression reflecting the same disorder
MECHANISM OF ACTION OF SSRIs

 Depressed state: low 5HT, upregulated receptors, low number of signals in the neuron to
release more 5HT.

 Antidepressant action: antidepressant blocks 5HT reuptake both at the dendrites and at the
axon

 The increase in 5HT causes the autoreceptors to desensitize / downregulate

 Downregulation of the autoreceptors causes the neuron to release more 5HT at the axon.

 increase of 5HT at the axon causes the postsynaptic receptors to desensitize / downregulate,
reducing side effects
SSRIs INDICATIONS DOSE HALF LIFE SIDE-EFFECTS REMARKS

FLUOXETINE 20-80mg 2 wks Combination with olanzapine with

• Major depressive disorder
• Obsessive-compulsive disorder (OCD)
5HT 2C antagonism Could excellent
• Premenstrual dysphoric disorder contribute to results for bipolar depression, treatment
(PMDD) agitation,anxiety, and resistant
• Bulimia nervosa undesirable activation unipolar depression, and
• Panic disorder psychotic depression
• Bipolar depression [in combination ✽Add or initiate other antidepressants
with with caution for up to 5 weeks after
olanzapine (Symbyax)] discontinuing fluoxetine
• Treatment-resistant depression [in
combination with olanzapine
(Symbyax)]
• Social anxiety disorder (social phobia)
• Posttraumatic stress disorder (PTSD
NICE GUIDELINES

First-line
 Mood Stabiliser (Lithium/ Valproate)
 Olanzapine and fluoxetine (5/20 or 10/40)
 When initiating an antidepressant, a mood stabilizer should always be co-prescribed
 For patients with moderate or severe depression, prescribing an SSRI should be
considered
 When treatment response is not adequate, the addition of a second mood stabilizer, such
as lamotrigine, is advised.
 For psychotic symptoms, prescription of antipsychotic medications is advocated.
Second-line
 Increasing the dose of the anti-depressant.
 Switching to an alternative anti-depressant. (Mirtazapine or Venlafaxine)
 Adding Quetiapine, Olanzapine or Lithium if the patient is not already taking it.
 ECT is recommended only to achieve rapid and short-term improvement of severe symptoms, catatonia, and
treatment-resistance.
The other guidelines include

 American Psychaitric Association (APA)guidelines

 British Association for psychopharmacology (BAP) guidelines

 World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the

biological treatment of bipolar disorders
 NOVEL TREATMENTS
• OMEGA-3 FATTY ACIDS
–Controlled trials have suggested that there might be prophylactic
benefit for bipolar disorder , still it lacks proven benefit for bipolar
depression.
• DOPAMINE AGONISTS
–Dopamine receptor agonist pramipexole possesses antidepressant
properties.
–significantly more pramipexole-treated subjects than placebo-treated
subjects improved by at least 50% from their baseline Ham-D scores.
• TRANSCRANIAL MAGNETIC STIMULATION
–Overall, studies provide weak and preliminary evidence that rTMS may be
effective in the acute treatment of bipolar depression, but this needs to be
tested in further larger trials, with rTMS given at more optimal parameters
 NOVEL TREATMENTS contd…

• VAGUS NERVE STIMULATION

–Vagus nerve stimulation (VNS) was first developed as an
adjunctive treatment for medically refractory epilepsy before being
approved for medication-resistant depression.
–In VNS, an implanted stimulator sends electrical pulses to the left vagus
nerve in the neck via a subcutaneous wire.
–A pilot prospective, open-label, study found evidence of benefit over
12 months
• STEREOTACTIC ABLATION
–A recent study followed 16 patients with intractable bipolar
illness who underwent limbic leukotomy (subcaudate tractotomy
and cingulotomy).
–There is a decline in depression severity ,anxiety and negative
symptoms
 DEEP BRAIN STIMULATION – Observations show that a combination of low-intensity
DBS and multiple mood stabilizers might reduce induction of manic symptoms by DBS
when treating bipolar depression
 PHOTOTHERAPY - Bright light and dawn simulation have been reported beneficial for
some patients of bipolar depression
 SLEEP DEPRIVATION - Mood elevating effects of a night of total sleep deprivation
have been reported to be significantly more common in bipolar depression than unipolar
depression but these effects are generally transient and may also cause switch to mania
 TREATMENT RESISTANT BIPOLAR
DEPRESSION

Definition
 Failure to reach sustained symptomatic remission for 8 consecutive weeks after two
different treatment trials at adequate therapeutic doses with at least two recommended
monotherapy treatments or at least one monotherapy treatment and another combination
treatment.

 MTRBD included the same initial definition as TRBD, with the addition of failure of at
least one trial with an antidepressant, a psychological treatment and a course of
electroconvulsive therapy
T

TREATMENT RESISTANT BIPOLAR DEPRESSION

 Mood stabilizers:-
 Lamotrigine, Pregabalin
 Antipsychotics:-
 Aripiprazole
 Antidepressants:- Bupropion
 Other Agents:- ketamine, pramipexole, Methylphenidate, Dexamfetamine, Modafinil,
Oxycodone
ECT

 About two third of bipolar depression patients respond to ECT.

 ECT has superior efficacy to antidepressant medications for the treatment of depression
in general.
 Response to ECT is reported to be about 70% for bipolar I, 73% for bipolar II and about
88% for unipolar depression
 The risk of a manic switch with ECT is about 7%.
CONCLUSION

 Bipolar Disorder is a complex, chronic, recurrent lifelong illness. Focus should be on

treatment shift from short-term to long-term, from episodic to illness-based and from
syndromal to functional recovery. Successful outcome depends on use of a holistic
approach.
 The approach should include identification and addressing psychosocial factors
impacting compliance; treating co-morbid conditions; and using medications that are
effective, safe, and tolerable in the long term. Since bipolar illness is multidimensional,
successful management requires skillful combinations and psychosocial interventions.