Pharmacotherapy of bipolar depression: an update

Bipolar affective disorder is a virulent illness with high rates of recurrence, disability, social impairment, and suicide. Although the manic or hypomanic episodes define the disorder, the depressions are more numerous and less responsive to treatment. As the initial depressive episodes are commonly misdiagnosed, initiation of therapy with mood stabilizers is often delayed, increasing the likelihood of treatment-emergent affective switches on antidepressant monotherapy. The empirical basis for selecting treatments for people with bipolar depression is weak, and only the combination of olanzapine and fluoxetine has received US Food and Drug Administration (FDA) approval. Conventional mood stabilizers are preferred for first-line therapies, although atypical antipsychotics are increasingly used, and FDA approval of quetiapine is pending. Antidepressants--particularly selective serotonin reuptake inhibitors and bupropion--are indicated when mood stabilizers are ineffective and for "breakthrough" depressions.