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Am J Psychiatry. 2004 Feb;161(2):217-22.

Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials.

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Department of Psychiatry, University of Oxford, Warneford Hospital, UK.



The authors sought to determine the efficacy and acceptability of lithium for relapse prevention in bipolar disorder.


A systematic review and meta-analysis of randomized controlled trials comparing lithium with placebo in the long-term treatment of bipolar disorders was conducted. Data were obtained from searching the registers of the Cochrane Collaboration; reviewing reference lists, journals, and conference abstracts; and contacting authors, experts, and pharmaceutical companies. Outcomes investigated included risk of relapse (manic, depressive, and total) as well as risk of specific adverse effects and total withdrawal rates.


Five randomized controlled trials (770 participants) were included. Lithium was more effective than placebo in preventing all relapses (random effects relative risk=0.65, 95% CI=0.50 to 0.84) and manic relapses (relative risk=0.62, 95% CI=0.40 to 0.95). The protective effect of lithium on depressive relapses was smaller and was less robust (relative risk=0.72, 95% CI=0.49 to 1.07).


Lithium treatment reduces the risk of relapse in bipolar disorder. The preventive effect is clear for manic episodes, although it is equivocal for depressive episodes.

[Indexed for MEDLINE]

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