Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, led the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) Study.

WEST HAVEN, CT — The addition of an atypical anti-psychotic medication to an antidepressant regimen for veterans not responding to their current treatment led to greater improvement in symptoms of depression than switching to another antidepressant altogether.

That’s according to a VA-led clinical trial published recently in the Journal of the American Medical Association.1

“This is the largest study ever performed of ‘next-step’ pharmacotherapy for patients who did not have an adequate response to initial antidepressant pharmacotherapy,” said Paul B. Hicks, MD, PhD, vice dean and professor of psychiatry and behavioral sciences at the Texas A&M College of Medicine in Temple and one of 12 clinicans on the study’s executive committee. “This is the best and largest comparison of switching vs. augmentation strategies for ‘next-step’ pharmacotherapy that has been published. This study looks at the safety and efficacy of the use of a second-generation antipsychotic as an augmentation strategy for treatment-resistant depression.”

Results of the study, led by researchers from the VA New England Mental Illness Research, Education, and Clinical Center, at the VA Connecticut Healthcare System in West Haven indicated a significantly greater likelihood of near-complete relief of depressive symptoms during the 12-week acute-treatment phase.

The 12-week follow-up of a randomized clinical trial of 1,522 patients with major depressive disorder (85% men) unresponsive to previous antidepressant treatment found that 29% achieved remission after augmenting their antidepressant with the antipsychotic aripiprazole vs. 22% who switched to the antidepressant bupropion. Other remission comparisons were not significant.

Study authors suggested that augmentation with aripiprazole resulted in a statistically significant, but only modestly increased likelihood of remission during 12 weeks of treatment, compared with switching to bupropion alone.

The study was conducted from December 2012 to May 2015 at VHA medical centers among patients who were diagnosed with nonpsychotic major depressive disorder (MDD). Participants had been unresponsive to at least one antidepressant course meeting minimal standards for treatment dose and duration.

“Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased, likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy,” researchers concluded. “Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.”

  1. Mohamed S, Johnson GR, Chen P, Hicks PB, Davis LL, et. al. Effect of Antidepressant Switching vs. Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial. JAMA. 2017 Jul 11;318(2):132-145. doi: 10.1001/jama.2017.8036. PubMed PMID: 28697253