Millions of patients suffering from major depression get little relief from the first drug they are prescribed. A major new study of 1,522 patients at 35 U.S. Veterans Health Administration medical centers shows these patients benefit more from adding an antidepressant treatment than from switching to another one, researchers report July 11 in the journal JAMA.

“We found that among three strategies evaluated in this study evidence of the greatest symptom benefit was provided by adding an antipsychotic to previous antidepressant therapy,“ said lead author Dr. Somaia Mohamed, associate clinical professor of psychiatry at Yale University School of Medicine and of the VA Connecticut Healthcare System, West Haven, Connecticut.

Less than a third of 16 million Americans with major depression obtain relief of symptoms from the first drug prescribed. The new study of this population showed a remission rate of 28.9% of those who augmented initial treatment with the antipsychotic drug aripiprazole (Abilify) after 12 weeks. This was a significantly greater proportion than the 22% remission among patients who discontinued use of one antidepressant and switched to another (buproprion).

The group taking aripiprazole was also significantly more likely to show a clinically meaningful response to treatment than either switching to another antidepressant or adding another antidepressant to the original medication, the authors report.

“The study by Mohamed and colleagues is one of the very few definitive studies addressing this question and it suggests that that all options are not alike,” said Dr. John Krystal, the McNeil Professor and chair of the Yale Department of Psychiatry. “This study provides the type of detailed guidance that doctors need.”

Dr. Sidney Zisook of the VA San Diego Healthcare System and University of California–San Diego is co–lead of the study. Primary funding for the research was provided by VA Cooperative Studies Program of VA Research and Development.