Research Updates in Psychiatry

Research Updates in Psychiatry


Tamoxifen appears effective for mania.

Tamoxifen, an estrogen blocker that is approved for the treatment of breast cancer, successfully treated patients with mania in a placebo-controlled trial. The trial, which took place in Turkey and included a researcher trained at Massachusetts General Hospital, enrolled 66 patients with bipolar I disorder, in either a manic or mixed episode. Patients were randomly assigned to either tamoxifen (starting at 20 mg BID, and titrating up to 40 mg BID) or placebo. After three weeks of treatment, patients on tamoxifen showed a 5.8 point improvement on the Young Mania Rating Scale, and a 48% response rate, while those on placebo had a 1.5 point worsening on the YMRS and only a 5% response rate. Twenty percent of tamoxifen patients had mild to moderate side effects (Yildiz A et al., Arch Gen Psychiatry 2008;65:255- 263).

TCPR’s Take: Some readers are probably wondering what prompted these researchers to test tamoxifen for bipolar disorder. Aside from blocking estrogen receptors, it turns out that tamoxifen is a protein kinase C (PKC) inhibitor. Various animal studies have hinted that excessive PKC activation can disrupt the way the cortex regulates behavior, potentially leading to mania. Ergo, inhibit PKC, and you just might inhibit mania. This was actually the second controlled trial of tamoxifen for bipolar disorder; the first one was smaller, including only 16 patients. It found a robust benefit for the drug (Zarate C et al., Bipolar Disorders 2007;9:561-570). The current study isn’t huge (only 50 of the original 66 patients completed it), and tamoxifen is not without side effects, most notably nausea and hot flashes. Nonetheless, it is certainly a fall back option when other agents aren’t working.


Orally disintegrating Zyprexa appears to cause less weight gain.

A few studies have shown that orally disintegrating Zyprexa Zydis appears to cause less weight gain than standard Zyprexa, but they have been short term studies. This one-year study (which did not receive any industry funding) enrolled 26 patients, all of whom had schizophrenia or schizoaffective disorder, and all of whom had been stabilized on standard Zyprexa (average dose 13.9 mg/day). These patients ranged from overweight to obese, with an average BMI of 32.4, and an average weight of 96.2 kg (212 pounds). In this open trial, patients were switched to the equivalent dose of Zyprexa Zydis. Of the 22 patients who completed the trial, 82% lost weight, and the average weight loss at one year was 2.7 kg (5.9 pounds). Most of the weight loss occurred within the first three months (Chawl B and Luxton-Andrew H, Hum Psychopharmacol Clin Exp 2008;23:211-216).

TCPR’s Take: Because this was an open trial, some of this weight loss may have been due to the effects of expectancy rather than the effect of the change in formulation per se. Nonetheless, this represents the fifth study consistent with the theory that Zyprexa Zydis causes less weight gain than standard Zyprexa. Since Zydis disintegrates on contact with the tongue, much of it is absorbed in the bloodstream before reaching the stomach. If the Zyprexa causes weight gain by stimulating serotonin receptors in the stomach, Zydis may decrease weight gain by avoiding this hypothetical mechanism of action.


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A new study is consistent with FDA’s black box requirements for antidepressants.

The FDA now requires antidepressant drug makers to carry black box warnings about an increased risk of suicidality in children and young adults. As covered in the April TCPR, the FDA data indicated that antidepressants were most dangerous for children, and that the suicidogenic effects waned consistently with increasing age of patients. These warnings continue to incite controversy among psychiatrists. The March issue of Journal of Clinical Psychiatry carries a new study with a different data set in apparent support of the FDA’s action. Researchers searched a national Medicaid database for all patients aged 6 to 64 who made a suicide attempt after receiving treatment for depression (with or without antidepressants; rates of completed suicides were not reported) during 1999 and 2000. They identified 236 cases, and they then compared them with a control group of similar patients (matched for diagnosis and demographics) who had not made suicide attempts. The research question: were suicide attempters more likely to have been started on antidepressants than suicide non-attempters? They found that, indeed, antidepressant treatment was associated with a higher risk of suicide attempts, but only in children and adolescents (ages 6 to 18). For patients 19 to 64, antidepressants had no effect on suicidality, and for adult males specifically, antidepressants had a protective effect (Olfson M and Marcus SC, J Clin Psychiatry 2008;69:425-432).

TCPR’s Take: While one always has to be cautious when interpreting this type of observational research, given how in sync these findings are with the FDA analysis, we find the results quite convincing.

Research Updates in Psychiatry

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APA Reference
Psychiatry Report, T. (2013). Research Updates in Psychiatry. Psych Central. Retrieved on September 18, 2020, from


Scientifically Reviewed
Last updated: 5 Sep 2013
Last reviewed: By John M. Grohol, Psy.D. on 5 Sep 2013
Published on All rights reserved.