Biopolar disorders

Definition
Cyclic Manic-depressive illness
The cyclic mood disorder is
characterized by recurrent fluctuations
in mood, energy, and behavior
encompassing the extremes of human
experiences.

Introduction
Bipolar disorder one or more manic episodes
Unipolar disorder single episodes of
depression
Bipolar I- Manic ~ Depression episodes
Bipolar II- Hypomanic ~ Depression episodes
Risk <1.6%; late 20s

Etiopathogenesis
Genetic predisposition with major life events precipitate
an episode that brings biochemical changes
Genetic causes : 20% in first degree relatives; doubled
risk in children with one parent having affective disorder
Environmental factors: stress, loss of loved-ones
Changes in the sleep-wake cycle or light-dark cycle
Hyperthyroidism may precipitate a mania
Hypothyroidism may precipitate a depression

 Endocrine factors : hypothyroidism, cushings syndrome,

increased cortisol levels.
Drugs : anticonvulsants, antipsychotics, BZ,
antiparkinsonism agents, antidepressants, opiate
withdrawal
Physical illness: SLE, Pernicious anaemia, Neurological
disorders

Neuro theories
An excess of catecholamines (primarily NE
and DA) cause mania.
Deficiency of GABA dysregulation of
neurotransmitters (e.g., increased DA and NE
activity)
Imbalance in cholinergic-adrenergic activity
and may increase the risk of manic episodes.

Diagnosis
Beck depression rating scale
Hamilton depression rating scale
Dexamethasone suppression test:
1mg of dexamethaone inj suppress
cortisol for 24 hours (normal)
if elevated positive

Clinical manifestations
Depression fatigue or loss of energy, disturbed
sleep, inappropriate guilt, poor concentration, thought
of death or suicide, disturbed appetite, agitation or
slowing of speech
Mania Racing thoughts, rapid speech, grandiose
ideas, clothing flamboyant- bright colors
Beck depression inventory and Hamilton depression
rating scale

DSM IV criterias
Depression
5 or more of the symptoms present during the 2 week
period

Depressed mood most of the day

Diminished pleasure in all activities
Significant weight loss or gain
Insomnia/hypersomnia everyday
Psychomotor retardation/agitation everyday
Fatigue/loss of energy everyday
Diminished ability to think or concentrate
Recurrent thought of death

 Depression: I doubt completely my ability to do anything well. It

seems as though my mind has slowed down and burned out to the
point of being virtually useless. [I am] haunt[ed] with the
total, the desperate hopelessness of it all. Others say, "It's
only temporary, it will pass, you will get over it," but of course
they haven't any idea of how I feel, although they are certain
they do. If I can't feel, move, think or care, then what on earth
is the point?

Contd
The symptoms do not meet criteria for mixed episode
Causes impairment in social, occupational areas
Symptoms not due to direct physiological effect of a
substance or general medical condition

DSM IV criteria - Mania

Distinct mood of abnormality and persistently elevated,
expansive or irritable mood lasting at least 1 week
During the period of mood disturbances, 3 or more of the
following symptoms have persisted and have been present to
a significant degree
Inflated self-esteem or grandiosity
Decreased need for sleep
More talkative than usual
Flight of ideas
Distractibility
Abnormal sexual, social activities

Hypomania
At first when I'm high, it's tremendous ideas are fast
like shooting stars you follow until brighter ones appear.
All shyness disappears, the right words and gestures are
suddenly there uninteresting people, things become
intensely interesting. Sensuality is pervasive, the desire
to seduce and be seduced is irresistible. Your marrow is
infused with unbelievable feelings of ease, power, wellbeing, omnipotence, euphoria you can do anything but,
somewhere this changes.

Mania
The fast ideas become too fast and there are far too
many overwhelming confusion replaces clarity you
stop keeping up with itmemory goes. Infectious humor
ceases to amuse. Your friends become frightened.
everything is now against the grain you are irritable,
angry, frightened, uncontrollable, and trapped.

 Symptoms do not meet the criteria for a mixed

episode
Impairment of occupational functioning
Symptoms not due to drug, underlying medical
conditions

Goal of treatment
Eliminate mood episode with complete
remission of symptoms (i.e., acute
treatment)
Prevent recurrences or relapses of
mood episodes (i.e., continuation phase
treatment)
Return to complete psychosocial
functioning

Non pharmacological treatment

Psychotherapy education
Adequate nutrition, sleep, exercise, and
stress reduction
Electroconvulsive therapy [ECT],
high-intensity bright light therapy,
Partial or complete sleep deprivation)

Pharmacotherapy

Lithium,
Valproate,
Carbamazepine, oxcarbazepine,
Lamotrigine,
Atypical antipsychotics,
Adjunctive agents such as
antidepressants and benzodiazepines.

Lithium carbonate
9002400 mg/day in 24 divided doses,
preferably with meals
Enhances GABAergic activity and normalizes
GABA levels
Check for thyroid, renal and cardiac function
before starting the therapy
Narrow therapeutic index drug (0.5-0.8 mmol/l)
Renal toxicity, thyrotoxicity, cardiotoxicity,
tremor, thirst, polyuria, weight gain, lethargy,
alopecia

Valproate
20 mg/kg per day
Increases GABA levels in plasma and
CNS; inhibits GABA catabolism,
increases synthesis, and release

Divalproax
7503000 mg/day (20 60 mg/kg per
day) in 23 divided doses for delayedrelease
divalproex or valproic acid.

Carbamazepine
2001800 mg/day in 24 divided doses.
Blocks voltage-sensitive Na+ channels
Alternative to lithium as a prophylaxis
Use alone or in combination with other drugs
(e.g., lithium,valproate, antipsychotics) for the
acute and long-term maintenance treatment of
mania or mixed episodes for bipolar I disorder.

Neuroleptics
Alone or combination with valproate
Haloperidol, chlorpromazine,
zuclopenthixol
Haloperidol : less Cardiac adverse effect;
less sedating; needs additional sedative to
control severe behaviour disturbance
Zuclopenthixol acetate (long acting
injection)

Treatment of depression
Moderate to severe depression :antidepressants
Mild depression : non-drug strategies
Must be taken for 4-6 weeks and treatment
should be continued for 6 month
Tricyclic antidepressants: blocks reuptake of
NE and 5HT
Imipramine upto 300 mg/day, well established,
can cause dry mouth, blurred vision, constipation

Antidepressants

Amitriptyline more sedative

Amoxapine less cardiotoxic, needs renal monitoring
Clomipramine potent 5 HT reuptake inhibitor
Dothiepin comparatively safer
Doxepin
lofepramine
Nortriptyline

 MAO inhibitors: inhibits the enzymes responsible for

oxidation of noradrenaline, 5HT and other biogenic
amines
Second line options; more effective in depressive
episodes with predominant anxiety symptoms
Drug-drug and drug-food interactions high!
Tranylcypromine high interactions
Phenelzine alternative to tranylcypromine, needs
hepatic monitoring
Isocarboxazid least potent, safe
Moclobemide less interactions

SSRIs: less side effects, efficacy?

Fluvoxamine
Fluoxetine long half life
Paroxetine high incidence of extrapyramidal reactions
Sertraline effective antidepressant, upto 150 mg
Citalopram

Miscellaneous :
Trazodone mixed serotonin agonist/antagonist. May
cause priapism
Nefazodone weak 5 HT and NE reuptake inhibitor;
lacks sexual dysfunction

 Mianserin safe. Needs blood count monitoring as it

may cause blood dyscrasias esp in elderly
Venlafaxine serotonin-NE reuptake inhibitor, safer
Reboxetine specific noradrenergic reuptake inhibitor
Mirtrazapine enhances both noradrenergic and
serotonergic transmission.
St.Johns wort (Hypericum perforatum)
ECT

Thank You !