Bipolar Disorder

SYNONYMS
Manic-depression
Cycloid psychosis
BASIC INFORMATION
Bipolar disorder is an episodic, recurrent, and frequently progressive condition in which the afflicted individual suffers periods of mania and, possibly, depression. Depressive episodes are not essential for the diagnosis. However, the individual must experience at least one manic episode in which he / she experiences at least 1 week of continuous symptoms of elevated, expansive, or irritable mood in association with three or four of the following:
a). Decreased need for sleep;
b). Grandiosity;
c). Pressured speech;
d). Subjective or objective flight of ideas;
e). Distractibility;
f). Increased level of goal-directed activity;
g). Problematic behavior.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
a). Mania associated with psychomotor activation that is usually goaldirected but not necessarily productive;
b). Elevated and frequently labile mood;
c). Flight of ideas with rapid, loud, pressured speech;
d). Psychosis with delusions, hallucinations, and formal thought disorder possible;
e). Depressive episodes resembling major depression; however, retardation usually extreme;
f). Catatonia possible in severe cases.
GENETICS:
a). Concordance rates for monozygotic twins: 0.7 to 0.9, for dizygotic twins: 0.2 to 0.4;
b). Risk of offspring with one affected parent: 0.2 to 0.4, with two affected parents: 0.4 to 0.7;

c). Displays the phenomenon of genetic anticipation (earlier onset with successive generations), which is a hallmark phenomenon of trinucleotide repeat diseases;
d). CAG trinucleotide repeats increased by approximately 30 repeats but location unknown;
e). Displays a parent of origin effect in which there is a higher frequency of the disease in maternal relatives;
f). Susceptibility locus mapped to chromosome 18p.
LABORATORY TESTS
* Because of high rate of secondary manias, initial presentation to confirm health of all major organ systems (routine chemistries, complete blood count, urinalysis, sedimentation rate);
* Low threshold for examination of CSF.
IMAGING STUDIES
Imaging of anatomy (CT scan or MRI) as well as function (EEG) should be part of initial workup.
ETIOLOGY
* Unknown
* Hypotheses:
a). Abnormalities of membrane function;
b). Second messenger abnormalities;
c). Noradrenergic excess.
DIAGNOSIS
The diagnosis of mania includes toxic effects of stimulant or sympathomimetic drugs as well as secondary mania induced by hyperthyroidism, AIDS, or neurologic disorders, such as Huntington’s or Wilson’s disease, or cerebrovascular accidents. Comorbidity with alcohol and substance abuse is common, either because of poor judgment and increased impulsivity or because of an attempt to self-treat the underlying mood symptoms and sleep disturbances.
DIFFERENTIAL DIAGNOSIS
a). Secondary manias caused by medical disorder (for example: renal disease, AIDS, stroke, digoxin toxicity) are frequent.
b). Onset of mania after age 40 years is suggestive of secondary mania.
c). Less severe, and probably distinct, conditions of bipolar type II and cyclothymia are possible.
d). Cross-sectional examination of acutely manic patient can be confused with schizophreniform or a paranoid psychosis.
WORKUP
a). History;
b). Physical examination;
c). Mental status examination.
TREATMENT
NONPHARMACOLOGIC THERAPY
a). Psychotherapy to help patients cope with consequences of the disease and improve compliance with medications;
b). Bright light therapy in the northern latitudes in individuals exhibiting a seasonal pattern of winter depression.
ACUTE GENERAL Rx
a). First-line agents for acute mania: lithium, valproate, carbamazepine lamotrigine, and olanzapine;
b). Useful adjuncts to acute treatment: antipsychotics and benzodiazepines;
c). Problematic because antidepressants can induce manic episodes.

CHRONIC Rx
a). Goal of long-term treatment: prevention;
b). Best agents for prophylaxis: lithium, valproate, and carbamazepine;
c). Useful second-line agents: antipsychotics (particularly the atypical agents such as clozapine);
d). Long-term use of antidepressants: frequently destabilizes patient and leads to more frequent relapses;
DISPOSITION
a). Course is variable.
b). Over 93% of patients having a single manic episode are likely to experience others.
c). Uncontrolled manic or depressive episodes can lead to additional episodes (“illness begets illness”).
d). Untreated suicide rate approaches 25%; drops to only 7% to 9% with treatment.
e). Psychosocioeconomic consequences of both mania and depression can be severe and disabling.

Prevention in bipolar disorders

Since bipolar illnesses tend to be relapsing and remitting, prevention of recurrence is the major therapeutic challenge in management. A patient who has experienced more than two episodes of affective disorder within a 5-year period is likely to benefit from preventative treatments. Recommendations include lithium, olanzapine, and valproic acid (so long as the patient is not a woman at risk of pregnancy).

Lithium (carbonate or citrate)

is one of the two main agents used for prophylaxis in patients with repeated episodes of bipolar illness. It is rapidly absorbed into the gastrointestinal tract and more than 95% is excreted by the kidneys; small amounts are found in the saliva, sweat and breast milk. Renal clearance of lithium correlates with renal creatinine clearance. Lithium is a mood-stabilizing drug that prevents mania more than depression. It reduces the frequency and severity of relapses by half and significantly reduces the likelihood of suicide. Its mode of action is unknown, but lithium is known to act on the serotoninergic system. Poor responses to lithium are associated with a negative family history, an unstable premorbid personality, and a rapid cycling illness. Recent pharmacogenetic work suggests that certain polymorphisms may predict response.