Breast Cancer Drug Tamoxifen May Decrease Mania Of Bipolar Disorder

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
Psychiatry.



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, AysegГјl Yildiz, M.D. (Dokuz EylГјl
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 authors state that tamoxifen and the placebo were well-tolerated.
"Moreover, all subjects used less lorazepam as the trial progressed,
and the rate of decrease was 2.5 times greater with tamoxifen."



"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

AysegГјl Yildiz; Sebnem Guleryuz; Donna Pauler Ankerst; Dost-ngГјr;
Perry F. Renshaw

Archives of General Psychiatry. (2008).
65(3):255-263.

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Written by: Peter M Crosta