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Tamoxifen shows promise for mania episodes in bipolar disorder

Tamoxifen — a drug commonly used for breast cancer — shows potential as a treatment for episodes of mania in patients with bipolar disorder, according to a systematic review and meta-analysis published in Journal of Psychopharmacology.

Other than lithium, all FDA-approved bipolar disorder treatments were first developed for other indications, according to Jorge Palacios, MD, PhD, from the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, and colleagues.

“Tamoxifen has been recommended as a potential option for pharmacological treatment of acute mania in some, but not all recent guidelines,” they wrote. “The extensive use of tamoxifen for other indications means it has a relatively well characterized safety profile, generally well tolerated but with some rare serious adverse effects.”

Tamoxifen inhibits the intracellular action of protein kinase C, similar to well-established treatments like lithium and valproate, according to the researchers.

In this study, Palacios and colleagues searched online clinical databases for randomized controlled trials that compared tamoxifen with placebo or alternative pharmacological treatments (eg, lithium, valproate or dopamine antagonists) in the management of bipolar disorder in adults, then synthesized their results using meta-analysis. Primary outcome was efficacy of tamoxifen on acute manic episodes.

The researchers identified five placebo-controlled randomized controlled trials of tamoxifen for the treatment of acute mania; they were 3 to 6 weeks in duration and included 164 participants overall. Tamoxifen was studied as a monotherapy in two trials and as augmentation of lithium or valproate in three trials.

Analysis revealed that tamoxifen outperformed placebo in change in mania scale scores (SMD = –2.14; 95% CI, –3.39 to –0.89) and endpoint mania scale scores (SMD = 1.23; 95% CI, 0.6-1.87).

Participants with bipolar disorder randomized to receive tamoxifen also had higher response rates (RR = 4.35; 95% CI, 1.999.5), with a trend toward greater effect in monotherapy studies (RR = 7.76; 95 % CI, 1.97-30.6) than augmentation studies (RR = 3.29; 95% CI, 1.27-8.52). In addition, the overall acceptability for tamoxifen was similar to placebo in the five studies (RR = 1.03; 95% CI, 0.94-1.13).

“Despite the promising results found so far, and the important gaps in our knowledge, there appears to be a lack of ongoing studies with tamoxifen for bipolar disorder at present,” the investigators wrote. “Future studies could investigate the effects of tamoxifen as an adjunct to dopamine antagonist medications for improved antimanic efficacy, and establish its longer-term effects on mood, particularly depression, and relapse.” – by Savannah Demko

Disclosure: Palacios reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.