Tamoxifen, which is used widely as an anti-estrogen agent in treatment of breast cancer, may be able to decrease symptoms of mania in patients with bipolar disorder, according to an article in the March issue of the Archives of General Psychiatry.

The small, three-week trial was based on the knowledge that tamoxifen also inhibits the actions of the protein kinase C family of enzymes. Abnormal levels of activity by these enzymes have been associated with bipolar disorder and symptoms such as distractibility, impaired judgment, and disorganized thoughts. Animal studies and human pilot trials have suggested that tamoxifen may be effective in treating mania in patients with bipolar disorder.

In the current work, Ayoegul Yildiz, MD, of the Dokuz Eylul University Medical School, Izmir, Turkey, and colleagues conducted a clinical trial with 66 patients age 18 to 60 years, all of whom were diagnosed with bipolar disorder and were currently in a manic or mixed state that included mania. Participants were randomized to tamoxifen (40 to 80 mg daily) or identical placebo tablets twice daily for up to three weeks. Participants in both groups also were given up to 5 mg per day of lorazepam as needed to control symptoms.

A total of 50 patients-29 assigned to tamoxifen and 21 assigned to 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 slightly increased scores.

Almost half (48 percent) of the tamoxifen patients responded to the drug, defined as a reduction of at least half in mania scores, compared with 5 percent of placebo patients, and 28 percent versus zero achieved cutoff scores for mania remission.

Patients taking tamoxifen also used less lorazepam-an average of 25.2 mg compared with 41.8 mg 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 wrote. 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 concluded.