Abstract
BackgroundIn a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; however, the effect was equivocal for depressive episodes. Since then, the evidence base has grown further. In this update, we furthermore present the data on efficacy of lithium in comparison to alternative drug treatments. In addition, we analyze the data comparing lithium with placebo and other treatments regarding drop-outs due to reasons other than a mood episode and completion of study (no mood episode and no drop-out to reasons other than a mood episode).MethodsRandomized controlled trials (RCTs) were sought comparing lithium with placebo and lithium with an alternative treatment in bipolar disorders where the stated intent of treatment was prevention of mood episodes. To this purpose, the Cochrane Central Register of Controlled Trials (CENTRAL) was searched. Reference lists of relevant papers and major textbooks of mood disorders were examined. Authors, other experts in the field, and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished.ResultsFor the comparison of lithium with placebo, seven trials (1,580 participants) were included. Lithium was more effective than placebo in preventing overall mood episodes (random effects RR 0.66, 95% CI 0.53 to 0.82), manic episodes (random effects RR 0.52, 95% CI 0.38 to 0.71), and, dependent on the type of analyses applied, depressive episodes (random effects RR 0.78, 95% CI 0.59 to 1.03; fixed effect RR 0.73, 95% CI 0.60 to 0.88). Lithium was inferior to placebo in leading to drop-outs for reasons other than a mood episode (random effects RR 1.33, 95% CI 1.07 to 1.65) but superior to placebo on study completion (random effects RR 1.69, 95% CI 1.12 to 2.55).For the comparison of lithium with anticonvulsants, seven trials were included (n = 1,305). In prevention of manic episodes, lithium showed superiority compared to anticonvulsants (random effects RR 0.66, 95% CI 0.44 to 1.00). However, there was no significant difference regarding prevention of overall mood episodes, depressive episodes, dropping-out to reasons other than a mood episode, or study completion.ConclusionsThe evidence base for lithium in the long-term treatment of bipolar disorders has strengthened. With no other drug available having such ample and consistent evidence for its efficacy lithium remains the most valuable treatment option in this indication.
Highlights
In a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; the effect was equivocal for depressive episodes
In the latest previous systematic review and metaanalysis which dates back to 2004 (Geddes et al 2004), we found evidence from randomized controlled trials including 770 participants that lithium treatment reduces the risk of mood episodes in bipolar disorders
Two trials were similar in design except that one recruited patients who had recently recovered from a depressive episode (Calabrese et al 2003) and the other recruited patients who had recently recovered from a manic or hypomanic episode (Bowden et al 2003)
Summary
In a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; the effect was equivocal for depressive episodes. In this update, we present the data on efficacy of lithium in comparison to alternative drug treatments. Long-term treatment to prevent mood episodes (relapse during continuation treatment as well as recurrences during maintenance/prophylactic treatment) is of vital importance in the management of bipolar disorders. Lithium has become a mainstay of preventative treatment in bipolar disorders, as well as in unipolar depression (Cipriani et al 2006). Lithium has been recommended for the treatment of acute mania and for the augmentation of antidepressants in unipolar depression (Katona 1995; Bauer et al 2014). This review focuses on the use of lithium to prevent mood episodes in bipolar disorders
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