by Anthony J. Brown, MD

Last Updated: 2007-09-14 10:58:17 -0400 (Reuters Health)

NEW YORK (Reuters Health) – The commonly used breast cancer drug tamoxifen may be an effective treatment for the acute mania seen with bipolar disorder, findings from a pilot study suggest. Moreover, it may provide more rapid relief than currently used drugs like lithium and valproate.

"This is the first time a drug has proven to be efficacious in acute mania based on work on molecular pharmacology," Dr. Carlos A. Zarate, Jr. and colleagues, from the National Institutes of Health in Bethesda, Maryland, told Reuters Health.

"This path of development from the molecular target to humans is quite exciting because it shows that this target could be useful in developing the next generation of antimanic agents rather than simply borrowing drugs from other disorders and hope they are effective in bipolar disorder," he added.

Previous research has suggested that inhibition of protein kinase C could be useful in combatting acute mania. Although there is evidence that both lithium and valproate inhibit protein kinase C, this appears to be an indirect effect. At present, there is only one relatively selective inhibitor of this enzyme that crosses the blood-brain barrier and has been used in humans: tamoxifen.

In an earlier open-label study, Dr. Zarate’s team had shown that tamoxifen could curb manic symptoms in a relatively short period of time, between 3 and 7 days.

The present investigation, a double-blind, controlled study, involved 16 patients with acute mania who were referred from inpatient psychiatric units in the Washington, DC area. The subjects included 14 males and 2 females, who were a mean of 35.4 years old, and were in good physical health.

They were treated with tamoxifen (20 mg/day to 140 mg/day) or placebo for 3 weeks. A treatment response was defined as a 50% or greater drop in Young Mania Rating Scale scores from baseline.

The authors report their findings in the September issue of Bipolar Disorders.

As early as 5 days after starting therapy, tamoxifen users showed significant improvements in mania compared with controls. Moreover, this benefit persisted throughout the entire trial period.

At the end of treatment, the response rate with tamoxifen was 63% compared with 13% for placebo.

"We now have proof of principle," study co-author Dr. Husseini K. Manji said in a statement. "Our results show that targeting protein kinase C directly, rather than through the trickle-down mechanisms of current medications, is a feasible strategy for developing faster-acting medications for mania. This is a major step toward developing new kinds of medications."