Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania

Abstract Background Considerable amount of biochemical data supports the potential involvement of protein kinase C in the pathophysiology and treatment of bipolar disorder. The aim of this double-blind, placebo-controlled study was to investigate the efficacy and tolerability of tamoxifen as an adjunct to lithium for the treatment of acute mania in hospitalized bipolar patients. Methods Eligible participants were 40 inpatients, between the ages of 19 and 49 years with current manic episode. Patients were randomly allocated to lithium (1–1.2 mEq/L) + tamoxifen 80 mg/day (group A) or lithium (1–1.2 mEq/L) + placebo (group B) for a 6-week, double-blind, placebo-controlled study. The principal measure of outcome was the Young Mania Rating Scale. The raters used standardized instructions for Young Mania Rating Scale. Results Young Mania Rating Scale scores improved with tamoxifen. The difference between the two protocols was significant as indicated by the effect of the group, the between-subjects factor ( F  = 5.41, df  = 1, p  = 0.02). A significant difference was observed on the Positive and Negative Syndrome Scale total score at week 6 in the two groups. The difference between the two groups in the frequency of side effects was not significant except for fatigue that occurred more often in the tamoxifen group. Limitations Tamoxifen is an antagonist of estrogen receptor as well. Conclusion The results demonstrate that the combination of tamoxifen with lithium was superior to lithium alone for the rapid reduction of manic symptoms. The combined use of tamoxifen with lithium was well tolerated in these acutely manic patients.