Tamoxifen: A Protein Kinase C Inhibitor to Treat Mania: A Systematic Review and Meta-Analysis of Randomized, Placebo-Controlled Trials

The aim of this study was to conduct a systematic review of literature to retrieve all randomized controlled trials that evaluated the efficacy of tamoxifen on manic mood episodes and meta-analyze their quantitative results. Four electronic databases were systematically searched from their inception to March 2014: PubMed, Cochrane Library (Cochrane Central Register of Controlled Trials), Scopus, and PsychINFO. Pooled difference in means of changes in mania scores and pooled odds ratio of treatment response (for tamoxifen monotherapy) were calculated as the main effect size. A random effects model was used to pool the data across studies. Quantitative syntheses were expressed by forest plots. Five randomized controlled trials (3 adjunct trials and 2 monotherapy trials) were included. Regarding adjunct tamoxifen, the standardized difference in mean of mania score changes in tamoxifen arm as compared with control arm was 0.669 (95% confidence interval [CI], 0.15-1.189; P = 0.012). Regarding monotherapy, the pooled difference in means of mania score changes in the tamoxifen arm as compared with the placebo arm was 22.09 (95% CI, 20.98-23.192; P < 0.000000001). Pooled odds ratio of response to treatment was 15.36 (95% CI, 2.99-78.73; P = 0.001) in the tamoxifen group as compared with the placebo group. Tamoxifen can be considered an effective treatment for manic bipolar patients. Making a conclusion regarding the efficacy and safety for longer periods warrants further studies with a larger sample size and longer follow-up duration.