Tamoxifen for Bipolar Disorder: Systematic Review and Meta-analysis

Background: Tamoxifen is an oral medication that has been proposed as a potential treatment for bipolar disorder. Tamoxifen acts to inhibit the intracellular action of protein kinase C, which is also an action of well-established treatments such as lithium and valproate. Here we aimed to identify randomised controlled trials (RCTs) of tamoxifen in the treatment of bipolar disorder and synthesise their results using meta-analysis.

Methods: RCTs were identified by searching of electronic databases and from discussion with experts in the field. Data were extracted, and meta-analyses performed in R.

Results: Five placebo-controlled RCTs of tamoxifen in the treatment of acute mania were identified. There were no trials in the treatment of episodes of bipolar depression, or for relapse prevention. The studies of mania treatment were of between three and six weeks duration. Tamoxifen was studied either as monotherapy (two trials) or as augmentation of lithium or valproate (three trials). Change in mania scale scores favoured tamoxifen over placebo: SMD -2.14 (95% CI -3.39 to -0.89; 4 trials), as did endpoint mania scale scores SMD 1.23 (95% CI 0.60-1.87; 5 trials). Response rates were also higher: RR 4.35 (1.99-9.50; 4 trials). Acceptability was similar to placebo: RR 1.03 (0.94-1.13; 5 trials).

Conclusions: Tamoxifen appears to be a promising potential treatment for episodes of mania. Future studies could investigate its effects as an adjunct to dopamine antagonists for improved anti-manic efficacy, and establish its longer term effects on mood, particularly depression and relapse.