Tamoxifen, an estrogen blocker that is approved for the treatment of breast can- cer, successfully treated patients with mania in a placebo-controlled trial. The trial, which took place in Turkey and included a researcher trained at Massachusetts General Hospital, enrolled 66 patients with bipolar I disorder, in either a manic or mixed episode. Patients were randomly assigned to either tamoxifen (starting at 20 mg BID, and titrating up to 40 mg BID) or placebo. After three weeks of treatment, patients on tamoxifen showed a 5.8 point improvement on the Young Mania Rating Scale, and a 48% response rate, while those on placebo had a 1.5 point worsening on the YMRS and only a 5% response rate. Twenty percent of tamoxifen patients had mild to moderate side effects (Yildiz A et al., Arch Gen Psychiatry 2008;65:255- 263).

TCPR’s Take: Some readers are probably wondering what prompted these researcherstotesttamoxifenforbipolardisorder. Asidefromblockingestrogenrecep- tors, it turns out that tamoxifen is a protein kinase C (PKC) inhibitor. Various animal studies have hinted that excessive PKC activation can disrupt the way the cortex regu- lates behavior, potentially leading to mania. Ergo, inhibit PKC, and you just might inhibit mania. This was actually the second controlled trial of tamoxifen for bipolar disorder; thefirstonewassmaller,includingonly16patients. Itfoundarobustbenefitforthe drug (Zarate C et al., Bipolar Disorders 2007;9:561-570). The current study isn’t huge (only 50 of the original 66 patients completed it), and tamoxifen is not without side effects, most notably nausea and hot flashes. Nonetheless, it is certainly a fall back option when other agents aren’t working.