LITHIUM, MOOD STABILIZING DRUGS, & OTHER TREATMENT FOR BIPOLAR DISORDER
Bipolar disorder, once known as manic-depressive illness, was conceived of as a psychotic disorder distinct from schizophrenia at the end of the 19th century. Before that both of these disorders were considered part of a continuum. It is ironic that the weight of the evidence today is that there is profound overlap in these disorders. This is not to say that there are no pathophysiologically important differences or that some drug treatments are differen-tially effective in these disorders. According to DSM-IV, they are separate disease entities while research continues to define the dimensions of these illnesses and their genetic and other biologic markers.Lithium was the first agent shown to be useful in the treatment of the manic phase of bipolar disorder that was not also an anti-psychotic drug. Lithium has no known use in schizophrenia. Lithium continues to be used for acute-phase illness as well as for prevention of recurrent manic and depressive episodes.
A group of mood-stabilizing drugs that are also anticonvulsant agents has become more widely used than lithium. It includes carbamazepine and valproic acid for the treatment of acutemania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarba-zepine, and topiramate are sometimes used to treat bipolar disor-der but are not approved by the Food and Drug Administration for this indication. Aripiprazole, chlorpromazine, olanzapine,quetiapine, risperidone, and ziprasidone are approved by theFDA for treatment of the manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for treatment of bipolar depression.
Bipolar affective (manic-depressive) disorder occurs in 1–3% of the adult population. It may begin in childhood, but most cases are first diagnosed in the third and fourth decades of life. The key symptoms of bipolar disorder in the manic phase are excitement, hyperactivity, impulsivity, disinhibition, aggression, diminished need for sleep, psychotic symptoms in some (but not all) patients, and cognitive impairment. Depression in bipolar patients is phe-nomenologically similar to that of major depression, with the key features being depressed mood, diurnal variation, sleep disturbance, anxiety, and sometimes, psychotic symptoms. Mixed manic and depressive symptoms are also seen. Patients with bipolar disorder are at high risk for suicide.
The sequence, number, and intensity of manic and depres-sive episodes are highly variable. The cause of the mood swingscharacteristic of bipolar affective disorder is unknown, although a preponderance of catecholamine-related activity may be present. Drugs that increase this activity tend to exacerbate mania, whereas those that reduce activity of dopamine or norepinephrine relieve mania. Acetylcholine or glutamate may also be involved. The nature of the abrupt switch from mania to depression experienced by some patients is uncertain. Bipolar disorder has a strong famil-ial component, and there is abundant evidence that bipolar disor-der is genetically determined.
Many of the genes that increase vulnerability to bipolar disor-der are common to schizophrenia but some genes appear to be unique to each disorder. Genome-wide association studies of psy-chotic bipolar disorder have shown replicated linkage to chromo-somes 8p and 13q. Several candidate genes have shown association with bipolar disorder with psychotic features and with schizophre-nia. These include genes for dysbindin, DAOA/G30, disrupted-inschizophrenia-1 ( DISC-1), and neuregulin 1.