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Drug Therapy in the Prevention of Recurrences in Unipolar and Bipolar Affective Disorders:  Report of the NIMH Collaborative Study Group Comparing Lithium Carbonate, Imipramine, and a Lithium Carbonate-Imipramine Combination

Robert F. Prien, PhD; David J. Kupfer, MD; Peter A. Mansky, MD; Joyce G. Small, MD; Vicente B. Tuason, MD; Carlyle B. Voss, MD; Wayne E. Johnson
Arch Gen Psychiatry. 1984;41(11):1096-1104. doi:10.1001/archpsyc.1983.01790220086014.
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• In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.

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