How to Treat Depression in Veterans

By Temma Ehrenfeld @temmaehrenfeld
September 23, 2017

Doctors should consider this antipsychotic drug sooner for a more effective treatment for depression in veterans, according to research.

Millions of people with major depression get too little relief from the first prescription they try, which seems to do the job entirely in less than a third of all cases. Typically, your doctor will suggest another antidepressant or you might add it on and take two.   

Many people search for the right antidepressant or combination for months or even years. Nearly a third never find relief. One option that may surprise you is an antipsychotic. A large study has now shown that adding the antipsychotic aripiprazole (Ablify) to your antidepressant might work better than two antidepressants. In this study, the depressed patients, a group of middle-aged veterans, mainly men, did not have psychosis.

The Food and Drug Administration has approved three antipsychotics as add-ons for depressed patients, but surveys of psychiatrists suggest that they usually don’t try this until three other treatments have failed. The research suggests they might consider it sooner, observes Harvard Medical School psychiatrist Maurizio Fava, MD, in an editorial accompanying the study report in the July 11, 21017 issue of the Journal of the American Medical Association.


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Led by Somaia Mohamed, MD, PhD, associate clinical professor of psychiatry at Yale University School of Medicine and of the VA Connecticut Healthcare System, in West Haven, Conn., the study took place at 35 U.S. Veterans Health Administration medical centers. More than 1,520 patients with non-psychotic major depression participated. All of them had failed to respond to at least one medication — and, on average, they had not found relief with more than two treatments. For the study, one group switched from the failed medication to an option often chosen because it tends not to affect sexual functioning: bupropion (Wellbutrin). Another group added bupropion to their current regime, and the third group added aripiprazole. The patients were evaluated after 12 weeks and 36 weeks.

After those first 12 weeks, 22.3 percent of the patients who switched were considered in remission, compared to 26.9 percent of the patients who added bupropion and 28.9 percent of the patients who added aripiprazole. The people taking aripiprazole were less likely to be anxious, but more likely to experience certain side effects: sleepiness, weight gain, and feeling restless or agitated.

Among those who experienced remission, there were no significant differences between the three groups when they were evaluated for relapse after 36 weeks.

Although most of them were men, Fava points to other research suggesting that aripiprazole might work even better in women.  

The antipsychotics now used as add-ons for depression belong to a generation that have fewer side effects than the older drugs, and the usual doses are much lower than someone might take to treat schizophrenia or bipolar disorder. However, elderly patients may be especially vulnerable, and all patients should be monitored closely. Taking antipsychotics for a long time can lead to a greater chance of diabetes along with weight gain, but this risk is lower with aripiprazole than with other drugs in its class.


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April 02, 2020

Reviewed By:  

Christopher Nystuen, MD, MBA