Prescribe Antidepressants to Patients With Bipolar Disorder?

Leslie Citrome, MD, MPH


October 17, 2013

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

Pacchiarotti I, Bond DJ, Baldessarini RJ, et al
Am J Psychiatry. 2013 Sep 13. [Epub ahead of print]

Report Summary

The International Society for Bipolar Disorders convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Overall, there is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. However, specific recommendations were made about classes of antidepressants. With respect to safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. Moreover, the frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. The task force recommended that in bipolar I patients, antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.


No antidepressants have been approved by the US Food and Drug Administration (FDA) for the treatment of bipolar disorder, including major depressive episodes associated with bipolar I or bipolar II disorder. Nevertheless, depressive symptoms can be severe in intensity, lead to marked impairments in psychosocial functioning, and are a significant risk factor for suicide. At present, quetiapine monotherapy (immediate- and extended-release formulations), olanzapine-fluoxetine combination, and lurasidone (monotherapy or in combination with lithium or valproate) are the only FDA-approved options. However, not everyone will respond to or tolerate these medications. Antidepressants may be necessary.

The task force commented that few well-designed, long-term trials of prophylactic benefits have been conducted, and the evidence is insufficient with respect to treatment benefits of antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. In the end, the task force provides some guidance consistent with common sense. For example, adjunctive antidepressants may be used for an acute bipolar I or II depressive episode when there is a history of previous positive response to antidepressants, and maintenance treatment with adjunctive antidepressants may be considered if a patient relapses into a depressive episode after stopping antidepressant therapy.



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