A small, three-week trial of tamoxifen, a drug typically used to treat breast cancer, indicates that it also may decrease symptoms of mania in patients with bipolar disorder, according to a report in the March issue of Archives of General Psychiatry, one of the JAMA/Archives journals.1
Tamoxifen interferes with the effects of the hormone estrogen, which accounts for its effects against breast cancer, according to background information in the article. However, tamoxifen also inhibits the actions of a family of enzymes known as protein kinase C. Abnormal levels of activity by these enzymes have been associated with bipolar disorder and related dysfunctions, such as distractibility, impaired judgments and disorganized thoughts.
Animal studies and human pilot trials have suggested that tamoxifen may be effective in treating mania—an abnormally elevated mood that features impulsive behavior, higher energy and activity levels, and disconnected thoughts—in patients with bipolar disorder. Ayşegül Yildiz, M.D., of the
A total of 50 patients—29 assigned to take tamoxifen and 21 assigned to take placebo—completed the 21-day trial. Patients in the tamoxifen group had significantly lower scores on tests used to measure the severity of mania at the end of the three-week period, while those in the placebo group had scores that slightly increased. Almost half (48 percent) of patients taking tamoxifen responded to the drug—defined as a reduction of at least half in mania scores—compared with 5 percent of those taking placebo, and 28 percent vs. zero achieved cutoff scores for mania remission.
Patients taking tamoxifen also used less lorazepam during the study—an average of 25.2 milligrams compared with 41.8 milligrams for patients in the placebo group. “Moreover, all subjects used less lorazepam as the trial progressed, and the rate of decrease was 2.5 times greater with tamoxifen,” the authors write. Both tamoxifen and placebo were well tolerated.
“The findings encourage further clarification of the role of protein kinase C in the pathophysiologic mechanism of bipolar 1 disorder and development of novel anti–protein kinase C agents as potential antimanic or mood-stabilizing agents,” the authors conclude.
“The role of tamoxifen per se in the treatment of bipolar disorder still remains to be determined, but its anti-estrogen effects are likely to present a safety challenge,” writes Mauricio Tohen, M.D., Dr.P.H., of
“The evidence-based selection of the therapeutic targets that led to this study hopefully will lead to similar approaches by industry, government and academia in the development of new and better treatments for bipolar disorder,” Dr. Tohen concludes. “Undoubtedly, this will be an important step to conquer this devastating disorder that affects millions of patients around the globe.”
1. Arch Gen Psychiatry. 2008; 65:255-263
2. Arch Gen Psychiatry. 2008; 65:252-253.