By Jawad Siddiqi (07-02)

CASE
Mrs. K. was a married lady of 27 years having two children with a family history of bipolar disorder in her father. In the past, at the age of 24 years, she had an episode of depression after the delivery of her second baby. She was taken to the hospital because she was very excited and talkative for 2 weeks. She was very agitated, could not sleep, talked almost incessantly and refused her food. Her endless conversation was mainly about films, actors and she interrupted it only to sing and dance. Continued

The doctor observed that Mrs. K. was tidily, even smartly, dressed. She appeared excited and irritable, with aggressive shouting. She was very talkative, and her speech was sometimes difficult to follow because she spoke very quickly, jumping from one topic to another. She felt superior to others, who were jealous because of her voice and beauty. She was easily distractible, but oriented to time, place and person. She did not show any impairment of memory or other cognitive functions. Physical and neurological examinations and laboratory investigations, including thyroid parameters, were all normal.

Diagnosis
Bipolar Affective Disorder with current episode of mania.

What is Bipolar Disorder?

It is one of the most common, severe and persistent

psychiatric illnesses.
Classically, periods of prolonged or profound

depression alternate with periods of excessively elevated and/or irritable mood (known as mania).

Important Definitions
Euthymia: A normal positive range of mood states implying

the absence of depression or elevated mood.

Dysphoria: An emotional state characterised by anxiety, Dysphoric mania: prominent depressive symptoms

depression, or unease. A state of feeling unwell or unhappy. superimposed on manic psychosis.

Euphoria: Intense elation with feelings of grandeur. Catatonia: a state of neurogenic motor immobility, and

behavioral abnormality manifested by stupor

 Cyclothymic disorder: A chronic disorder, with

duration of 2 or more years. Numerous hypomanic and minor depressive episodes, with few periods of euthymia (i.e., never symptom-free for more than 2 months.)
Mixed episode: Occurrence of both manic/hypomanic

and depressive symptoms in the same episode, every day for at least 1 week (DSM-IV TR) or 2 weeks (ICD10).

Epidemiology of Bipolar Disorder: Male = Female, (bipolar II and rapid cycling more common in females) Mean age of onset 1725 years Peaks at 1519 years and 2021 years; mean of 21 years

Classification and Diagnostic Criteria

ICD-10 criteria: Requires at least two episodes, one of

which must be hypomanic, manic or mixed.

DSM-IV TR criteria: Allows a single manic episode and

cyclothymic disorder to be classified as part of bipolar disorder. Defines two subtypes:

 Bipolar I disorder: One or more manic or mixed

episodes with or without history of one or more depressive episodes.

Bipolar II disorder: One or more depressive

episodes plus one or more hypomanic episodes without manic or mixed episodes.

Have similar symptoms to BP 1 but not severe enough to cause marked impairment in social or occupational functioning. Typically do not require hospitalization in order to assure the safety of the person.

What is Mania?
Mania is sometimes referred to as the other extreme to

depression.
Mania is an intense high where the person feels

euphoric, almost indestructible in areas such as personal finances, business dealings, or relationships.
They may have an elevated self-esteem, be more

talkative than usual, have flight of ideas, a reduced need for sleep, and be easily distracted.

Mania Cont
The high, although it may sound appealing, will often

lead to severe difficulties in these areas, such as spending much more money than intended, making extremely rash business and personal decisions, involvement in dangerous sexual behavior, and/or the use of drugs or alcohol.
Depression is often experienced as the high quickly

fades and as the consequences of their activities becomes apparent, the depressive episode can be exacerbated.

Etiology: Genetic

Biochemical
Psychosocial Etiological Theories

Genetic: Twins: 3390% concordance Children of one parent have a 50% chance of psychiatric illness.

Biochemical
Dysregulation of neurotransmitters at brain synapses:

Noradrenaline (NA), serotonin (5HT) and dopamine (DA) all have been implicated.
Abnormalities of biogenic amine metabolites.
Neuroendocrinal dysfunction . Given the effects of environmental stressors and exogenous

steroids, role has been suggested for glucocorticoids and other stress related hormonal responses.

Psychosocial
Stressful life events (major loses, disappointments,

deaths, divorces).
Pre-morbid personality types that use internalising

rather than externalising defense mechanisms.

Negative cognitive distortions about self, environment,

and life experiences.

Learned helplessness.

Etiological theories
Kindling: The older hypothesis that suggests a role of

neuronal injury through electrophysiological kindling and behavioural sensitisation similar to epilepsy.
Abnormal apoptosis: Abnormal programmed cell

death in critical neuronal network controlling emotions

Course
It is extremely variable. First episode in females tends to be

depressive and in males tends to be manic.

Untreated patients may have more than 10 episodes in a lifetime. As many as 60% of people diagnosed with bipolar I disorder

experience chronic interpersonal or occupational difficulties.

Stressful life events, changes in sleep-wake schedule, and current

alcohol or substance abuse may affect the course and lengthen the time to recovery.

Consequences if Untreated
High % have alcohol/substance dependence Suicide (up to 10% of bipolar patients commit suicide) Employment problems, financial problems Poor health, poor quality of life Marital disharmony, interpersonal problems

Differential Diagnosis (According to Episode)

Hypomania/Mania/Mixed Depression:
ADHD (Attention Deficit Hyperactivity Disorder), Compulsive Disorders (Shoplifting, etc) Impulse Control Disorders Schizophrenia, Personality Disorders, Substance Intoxication (stimulants hallucinogens, opiates)

Infection:
Tertiary syphilis
Influenza viral pneumonia

viral hepatitis
TB Multiple sclerosis

Head injury
Brain tumour,

Endocrine disorders:
Hypothyroidism Diabetes

Hyperparathyroidism
Cushings syndrome

Adrenal insufficiency
Hypopituitarism

Drugs
Corticosteroids
Contraceptives

Antihypertensive (beta blockers, reserpine)

Alpha methyldopa

Anticancer
Antipsychotics

Assessment
History:
Number of previous episodes Average length of episodes Level of psychosocial functioning in between episodes Previous response to treatment Family history of psychiatric problems Current and past use of alcohol and other drugs

InvestigationsFor organic/treatable cause

Blood CP-- for infectious etiology manifesting with

agitation or increased activity of mania.

Hormonal assays-- for mood symptoms in a patient

with signs of hypo/hyperthyroidism.

Electrolytes-- for confusional states presenting similar

to manic/catatonic excitement or depressive stupor.

 Brain imaging-- CT or MRI scan for suspected

dementia presenting as mood symptoms (e.g. disinhibition or pseudo-depression)

Serology-- e.g. testing for Venereal diease or HIV.

Treatment
Acute Manic/Mixed Episodes:
Lithium Good response, inexpensive. Antidepressant action, helps reduce suicide risk. Starting dose 300 mg t.i.d Do serum level after 5 days to adjust the dose.

 Carbamazepine Higher incidence of side effects Cheap with good efficacy Low risk of weight gain. Valproate Well tolerated with very few drug interactions. Loading dose of 20/mg/kg Weight gain risk.

 Antipsychotics Useful for rapid control of severely agitated or psychotic patients.

Risperidone Olanzapine Clozapine (for resistant cases, requires weekly blood

test)

Treatment for Bipolar Depressive

Bipolar Depressive Episode:
Treatment by mood stabiliser alone, or/and

antidepressants, Electroconvulsive therapy

Severely depressed/high suicidal risk/needing urgent

treatmentElectroconvulsive therapy may be considered first line

Drug free patient start mood stabiliser (e.g. lithium

or lamotrigine with antidepressant properties)

 Experts rely heavily on lithium and lamotrigine

Use caution with antidepressants (concern for the risk

of inducing hypomania and mania; and in recognition of lack of data supporting antidepressants in this role, versus lithium alone).

What is ECT?
Electroconvulsive therapy is a psychiatric treatment in

which seizures are electrically induced in anesthetized patients for therapeutic effect.
Today, used in the treatment of depression, mania and

catatonia that have not responded to other treatments.

(psychotron for electroshocks)

Prophylaxis
Aims to prevent recurrent episodes
Indicated in any patient with 2 or more episodes in

past 5 years
Lithium or Valproate may be the first line of treatment

Prognosis
Poor prognostic factors: drugs/alcohol abuse,

psychotic features, non-compliance, poor employment history, male sex, residual symptoms between episodes, long duration of episodes.
Good prognostic factors: later age of onset, few co-

morbid physical problem, good treatment response and compliance, full recovery between episodes, manic episodes of short duration.

References:
Psychiatry for General Practitioners by M.S. Bhatia
Kaplan & Sadocks- Synopsis of Psychiatry

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