Bipolar depression: issues in diagnosis and treatment.

Although bipolar affective disorder is defined by the history of manic or hypomanic episodes, depression is arguably a more important facet of the illness. Depressive episodes, on average, are more numerous and last longer than manic or hypomanic episodes, and most suicides occur during these periods. Misdiagnosis of major depressive disorder delays initiation of appropriate therapy, further worsening prognosis. Distinguishing features of bipolar depression include earlier age of onset, a family history of bipolar disorder, presence of psychotic or reverse neurovegetative features, and antidepressant-induced switching. Bipolar I depressions should initially be treated with a mood stabilizer (carbamazapine, divalproex, lamotrigine, lithium, or an atypical antipsychotic); antidepressant monotherapy is contraindicated. More severe or "breakthrough" episodes often require a concomitant antidepressant, such as bupropion or a selective serotonin reuptake inhibitor (SSRI). The first treatment specifically approved for bipolar depression is a combination of the SSRI fluoxetine and the atypical antipsychotic olanzapine. For refractory depressive episodes, venlafaxine, the monoamine oxidase inhibitor tranylcypromine, and ECT are most widely recommended. The optimal duration of maintenance antidepressant therapy has not been established empirically and, until better evidence-based guidelines are established, should be determined on a case-by-case basis.