Among patients unresponsive to an antidepressant medication, adding the antipsychotic aripiprazole modestly increased the likelihood of remission from depression compared to switching to the antidepressant bupropion, according to a study published by JAMA.

Major depressive disorder (MDD) is a chronic, debilitating disorder that affected an estimated 16 million adults in the United States in 2015. Less than one-third of patients achieve remission with their first antidepressant. Somaia Mohamed, M.D., Ph.D., of the VA Connecticut Healthcare System, West Haven, Conn., and colleagues randomly assigned 1,522 patients at 35 U.S. Veterans Health Administration medical centers diagnosed with MDD and unresponsive to at least one antidepressant to switch to a different antidepressant (; n = 511); augment current treatment with bupropion (n = 506); or augment with aripiprazole (n = 505) for 12 weeks (treatment phase) and evaluated for up to 36 weeks.

Among the (average age, 54 years; men, 85 percent), 75 percent completed the treatment phase. Depression remission rates at 12 weeks were 22.3 percent for the switch group, 26.9 percent for the augment-bupropion group, and 28.9 percent for the augment¬ aripiprazole group. Symptom improvement was greater for the augment-aripiprazole group than for either the switch group or the augment-bupropion group.

Anxiety was more frequent in the two bupropion groups.

Adverse effects more frequent in the augment-aripiprazole group included drowsiness, restlessness and weight gain."Given the small effect size and adverse effects associated with , further analysis including cost-effectiveness is needed to understand the net utility of this approach," the authors write.

A limitation of the study was that only one antidepressant and one antipsychotic were evaluated, and the generalizability of the results to other medications is unknown.