The drug tamoxifen is usually used to treat breast cancer, but
researchers say that it also may reduce symptoms of mania in people
with bipolar disorder. An article summarizing the small, three-week
trial of tamoxifen is published in Archives of General
As a treatment for breast cancer, tamoxifen impacts the way in which the hormone estrogen works in the body. In addition, tamoxifen works against the actions of the protein kinase C family of enzymes. People who have bipolar disorder and related dysfunctions - ability to be distracted, poor judgment-making abilities, and disorganized thoughts - have been associated with abnormal activity levels of these enzymes.
Patients with bipolar disorder often have mania, characterized by impulsive behavior, hyperactivity, and disconnected thoughts. Previous animal studies and human pilot trials have recommended tamoxifen as an effective treatment for these abnormally elevated moods.
To test tamoxifen as a treatment, Aysegül Yildiz, M.D. (Dokuz Eylül University Medical School, Izmir, Turkey) and colleagues conducted a clinical trial. The study consisted of 66 patients between 18 and 60 years old. All patients were diagnosed with bipolar disorder and at the time were experiencing mania or a mixed state that included mania as one component. The researchers randomly assigned participants to take either a) tamoxifen (40 milligrams to 80 milligrams per day) or b) identical placebo tablets twice daily for up to three weeks. All patients received up to 5 milligrams per day of lorazepam, a sedative that helps control symptoms.
Of the 66 patients who began the study, 50 patients completed the 21-day trial - 29 from the tamoxifen group and 21 from the placebo group. Results at the end of three weeks are summarized below:
- Tamoxifen takers scored significantly lower on tests measuring the severity of mania
- Placebo takers had mania scores that slightly increased
- 48% of patients taking tamoxifen responded to the drug (a reduction of at least half in mania scores)
- 5% of patients taking placebo responded to the drug
- 28% of tamoxifen takers vs. zero placebo takers had mania scores low enough for it to be considered in remission
- Tamoxifen patients used less lorazepam during the study (averaging 25.2 mg compared to 41.8 mg)
"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," conclude the authors.
Protein Kinase C Inhibition in the Treatment of Mania: A Double-blind, Placebo-Controlled Trial of Tamoxifen
Aysegül Yildiz; Sebnem Guleryuz; Donna Pauler Ankerst; Dost-ngür; Perry F. Renshaw
Archives of General Psychiatry. (2008). 65(3):255-263.
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Written by: Peter M Crosta