Treatment of depression in bipolar disorder: new directions for research.

The objective of the study was to review the clinical literature on the acute, somatic treatment of the depressed phase of bipolar disorder. We reviewed all available published studies of "standard" somatic treatments (lithium, antidepressant and anticonvulsant agents, and electroconvulsive therapy [ECT]) reporting three or more depressed bipolar patients who were not psychotic, rapid cycling, or previously treatment refractory. We also reviewed all studies of "nonstandard" pharmacologic treatments involving even a single case of a depressed bipolar patient. Data sources included the MEDLINE database and relevant references from articles obtained in this search and in major reviews. Five of seven studies comparing ECT with antidepressant agents find ECT more efficacious. Eight of nine controlled comparisons find lithium superior to placebo in depressed bipolar patients. Three controlled comparisons of lithium to tricyclic antidepressants suggest that lithium is equivalent to tricyclic drugs in such patients. Three double-blind, controlled studies indicate that carbamazepine is more effective than placebo. Limited data on other antidepressant classes suggest that monoamine oxidase inhibitors, bupropion, and serotonergic agents may offer some advantages over tricyclic antidepressants in this population. Some "nonstandard" treatments also show some potential in bipolar patients. The possibility of switching into a manic episode is an important consideration with many of the agents studied, although little remains known about spontaneous versus treatment-associated mood shifts. In contrast to the extensive literature on the acute treatment of the manic phase of bipolar disorder and on the prophylaxis of manic and depressive episodes, there are few studies of treatment of the depressed phase of bipolar disorder, and their results generally are limited or inconclusive. Lithium generated a revolution in psychiatric treatment, but the treatment of the depressed phase of bipolar disorder remains a relatively neglected corner of the field. Several study designs may help to augment knowledge in the treatment of bipolar depression.