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Lithium May Be an Effective Treatment for the Prevention of Relapses in Bipolar Disorder

Lithium may be an effective treatment for the prevention of relapses in bipolar disorder, suggests a review of new evidence.

Lithium served as the standard of treatment over several decades for the prevention of such relapses. However, evidence suggesting that the treatment may not be as effective as initially believed has resulted in a large discontinuation of lithium use, especially in North America.

"The discarding of lithium in North America is regularly lamented by many leading authorities in the treatment of bipolar disorder," writes John R. Geddes, MD, FRC Psych, from the University of Oxford, Warneford Hospital, United Kingdom. However, he stresses that any proposal for the continued use of lithium should be based on scientific evidence.

Several recent trials investigating new medicines for bipolar disorder have included a lithium comparison arm, providing modern scientific data for a new evaluation of the efficacy of the drug. The availability of these new studies prompted Dr. Geddes and colleagues to perform a systematic review and meta-analysis of randomised trials comparing lithium with placebo in the prevention of bipolar disorder relapse.

After screening 300 articles from multiple databases and registers, the researchers identified 5 randomised trials comparing lithium with placebo in 770 patients with bipolar disorder patients. The trials followed participants either until relapse or for a maximum of 11 months to 4 years with lithium levels between 0.5 and 1.4 mmol/L.

Based on a meta-analysis of the combined data, lithium was more effective than placebo in preventing any new episodes of mood disturbances (random effects relative risk [RR]=0.65, 95% confidence interval [CI]=0.50-0.84; P = .001). The average risk of relapse in the lithium group was 40%, compared with 60% for the placebo group.

The researchers also evaluated the efficacy of lithium in the prevention of relapse for specific types of mood disturbances. Lithium was found to be significantly more effective than placebo in the prevention of manic episodes (RR=0.62, 95% CI=0.40-0.95; P = .03). However, the effect of lithium on depressive relapse was smaller and did not reach statistical significance (RR=0.72, 95% CI=0.49-1.07;P = .20).

"This review supports the use of long-term lithium treatment to prevent relapse in patients with bipolar disorder, particularly in those patients for whom the main burden of disability is secondary to mania," the researchers conclude.

Furthermore, they emphasise that the data supports a moderate beneficial effect on depressive relapse even though the effect was not statistically significant. They suggest that at least some patients are likely to be protected against both manic and depressive relapses with lithium treatment.

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

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