Treatment of bipolar depression: current status, continued challenges, and the STEP-BD approach

This article takes an evidence-based medicinal approach to the treatment of bipolar depression. Mood stabilizers are strongly recommended as the first line of treatment for milder bipolar depressive episodes, primarily because subsequent preventive therapy will be necessary. In addition to lithium, recent research has established the antidepressant effects of lamotrigine and olanzapine. There is agreement that three presentations of bipolar I depression warrant combined antidepressant/ mood stabilizer strategies: episodes not responsive to mood stabilizers, episodes that "break through" despite prophylaxis, and markedly severe or psychotic episodes. Bupropion and selective serotonin reuptake inhibitors (of which fluoxetine and paroxetine have received the most extensive study) are uniformly considered the antidepressants of choice; venlafaxine and monoamine oxidase inhibitors rank highly for treatment-resistant cases. With concomitant mood stabilizer therapy, the risk of antidepressant-induced mania therapy is low (5%-10% during acute phase therapy with a selective serotonin reuptake inhibitor or bupropion). The optimal duration of antidepressant therapy is not known, and experts tend to recommend relatively short or indefinite courses of therapy based on factors such chronicity and past history of recurrence. The goals of the Systematic Treatment Enhancement Program for Bipolar Disorder (www.stepbd.org), which was sponsored by the National Institute of Mental Health are described in terms of filling several large gaps in knowledge that preclude a truly evidence-based approach to treatment of bipolar depression.