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Antimanic Response to Lithium Associated with Number of Previous Episodes

Research has shown that lithium has decreased prophylactic efficacy in bipolar patients with a history of multiple manic episodes and that patients with acute manic episodes have decreased response to lithium if their disorder involves mixed episodes or rapid cycling. In a parallel-group, randomized, and double-blind study, these investigators examined the relation between prior affective episodes and response to lithium, divalproax, and placebo in 165 acutely manic, hospitalized patients.

Patients with 7 or fewer previous manic episodes showed similar response levels to the 2 active treatments; response to lithium decreased in patients with over 7 episodes. Eleven or more previous episodes of mania or 4 or more episodes of depression predicted a worse response to lithium but not to divalproax. These associations were independent of the presence of either mixed states or rapid cycling.

Comment: Several important questions emerge: Why does poor response occur with lithium treatment but not with divalproax treatment after multiple episodes? Why is poorer response to lithium associated with fewer prior episodes of depression than mania? Possible explanations include mechanisms involving behavioral sensitization due to earlier differences in catecholamine output, development of tolerance to lithium, impact of earlier antidepressant treatment, or underlying lithium resistance related to the primary mechanisms of mood instability. The investigators did not report rates of comorbid alcoholism and substance abuse for patients in the study, although these comorbidities have been reported to be associated with nonresponse to lithium.

— J Yager

Published in Journal Watch Psychiatry July 5, 2000

Citation(s):

Swann A et al. Mania: Differential effects of previous depressive and manic episodes on response to treatment. Acta Psychiatr Scand 2000 Jun 101 444-451.

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