Biopolar disorders

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DefinitionCyclic Manic-depressive illness

The cyclic mood disorder is characterized by recurrent fluctuations in mood, energy, and behavior encompassing the extremes of human experiences.

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Introduction Bipolar disorder one or more manic episodesUnipolar disorder single episodes of depression

Bipolar I- Manic ~ Depression episodesBipolar II- Hypomanic ~ Depression episodes

Risk

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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

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Endocrine factors : hypothyroidism, cushings syndrome, increased cortisol levels.

Drugs : anticonvulsants, antipsychotics, BZ, antiparkinsonism agents, antidepressants, opiate withdrawal

Physical illness: SLE, Pernicious anaemia, Neurological disorders

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Neuro theoriesAn 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.

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DiagnosisBeck depression rating scaleHamilton depression rating scaleDexamethasone suppression test:

1mg of dexamethaone inj suppress cortisol for 24 hours (normal) if elevated positive

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Clinical manifestationsDepression 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

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DSM IV criteriasDepression 5 or more of the symptoms present during the 2 week periodDepressed mood most of the dayDiminished pleasure in all activitiesSignificant weight loss or gainInsomnia/hypersomnia everydayPsychomotor retardation/agitation everydayFatigue/loss of energy everydayDiminished ability to think or concentrateRecurrent thought of death

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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?

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

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DSM IV criteria - ManiaDistinct mood of abnormality and persistently elevated, expansive or irritable mood lasting at least 1 weekDuring the period of mood disturbances, 3 or more of the following symptoms have persisted and have been present to a significant degreeInflated self-esteem or grandiosityDecreased need for sleepMore talkative than usualFlight of ideas DistractibilityAbnormal sexual, social activities

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HypomaniaAt 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, well-being, omnipotence, euphoria you can do anything but, somewhere this changes.

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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.

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Symptoms do not meet the criteria for a mixed episodeImpairment of occupational functioningSymptoms not due to drug, underlying medical conditions

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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

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Non pharmacological treatment Psychotherapy educationAdequate nutrition, sleep, exercise, and stress reductionElectroconvulsive therapy [ECT], high-intensity bright light therapy,Partial or complete sleep deprivation)

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

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Lithium carbonate9002400 mg/day in 24 divided doses, preferably with mealsEnhances GABAergic activity and normalizes

GABA levelsCheck for thyroid, renal and cardiac function before starting the therapyNarrow therapeutic index drug (0.5-0.8 mmol/l)Renal toxicity, thyrotoxicity, cardiotoxicity, tremor, thirst, polyuria, weight gain, lethargy, alopecia

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Valproate20 mg/kg per dayIncreases GABA levels in plasma and CNS; inhibits GABA catabolism, increases synthesis, and release

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Divalproax7503000 mg/day (20 60 mg/kg per day) in 23 divided doses for delayed-release

divalproex or valproic acid.

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Carbamazepine

2001800 mg/day in 24 divided doses.

Blocks voltage-sensitive Na+ channelsAlternative 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.

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NeurolepticsAlone or combination with valproateHaloperidol, chlorpromazine, zuclopenthixolHaloperidol : less Cardiac adverse effect; less sedating; needs additional sedative to control severe behaviour disturbanceZuclopenthixol acetate (long acting injection)

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Treatment of depressionModerate to severe depression :antidepressantsMild depression : non-drug strategiesMust be taken for 4-6 weeks and treatment should be continued for 6 monthTricyclic antidepressants: blocks reuptake of NE and 5HTImipramine upto 300 mg/day, well established, can cause dry mouth, blurred vision, constipation

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AntidepressantsAmitriptyline more sedativeAmoxapine less cardiotoxic, needs renal monitoringClomipramine potent 5 HT reuptake inhibitorDothiepin comparatively saferDoxepinlofepramine Nortriptyline

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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 symptomsDrug-drug and drug-food interactions high!Tranylcypromine high interactionsPhenelzine alternative to tranylcypromine, needs hepatic monitoringIsocarboxazid least potent, safeMoclobemide less interactions

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SSRIs: less side effects, efficacy?FluvoxamineFluoxetine long half lifeParoxetine high incidence of extrapyramidal reactionsSertraline effective antidepressant, upto 150 mgCitalopram

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

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Mianserin safe. Needs blood count monitoring as it may cause blood dyscrasias esp in elderly Venlafaxine serotonin-NE reuptake inhibitor, saferReboxetine specific noradrenergic reuptake inhibitorMirtrazapine enhances both noradrenergic and serotonergic transmission.

St.Johns wort (Hypericum perforatum)

ECT

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Thank You !

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