Antidepressants and Bipolar I Affective Disorder

Michael E. Thase, MD


April 10, 2006

In This Article


Although the diagnosis of bipolar I affective disorder is formally defined by a history of at least 1 manic episode, it has become increasingly clear that effective management of depressive episodes is the greater clinical challenge.[1] Indeed, converging lines of evidence indicate that there is a great need for better therapies for bipolar depression. Recent survey data show that people with bipolar disorder spend more than 3 times as many days depressed as they do hypomanic or manic.[2] Moreover, people with bipolar I disorder spend an average of one third of their adult lives with depressive symptoms.[3] Not only does it take longer for patients to respond to depressive episodes than to mania, but in one study, the bipolar depressed were shown to be > 4 times more likely to remain ill at the end of 1 year of treatment than manic patients.[4]

Whereas patients with pure mania usually respond to treatment, patients with mixed episodes are the most likely to be treatment-resistant.[1] Even when treatment of bipolar depression is partially effective, residual depressive symptoms are associated with psychosocial disability[5] and a high risk of relapse.[6] And, of course, it is depression -- not mania -- that ultimately accounts for the high rate of suicide over the lifetimes of patients with bipolar disorder.[7]

Despite the magnitude of this problem, only 1 treatment -- the proprietary combination of olanzapine and fluoxetine -- has ever received the US Food and Drug Administration's (FDA) approval for the specific indication of bipolar depression. Moreover, whereas antidepressants are widely used to treat bipolar depression, it is not at all clear that studies of nonbipolar depression can be used to guide the treatment of bipolar I depression.[1] There have been only a handful of rigorously controlled studies in the area, and it is time to reassess the role of antidepressant therapies for bipolar I depression.


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