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Continuation of combination drug therapy for psychotic depression reduces relapse risk, JAMA study shows

UMass Medical School depression expert Anthony Rothschild explains findings

Anthony Rothschild

Anthony Rothschild, MD, is the lead researcher at UMass Medical School and one of four principal investigators on a new JAMA study that analyzes how continuation of a combination drug therapy could help patients who have major depressive disorder with psychotic features, a disabling condition with a high-risk of suicide.

“This is a very difficult patient population to treat and even more difficult to enroll in research studies,” said Dr. Rothschild, the Irving S. and Betty Brudnick Chair in Psychiatry and professor of psychiatry. Rothschild, along with colleagues at University Health Network, Toronto; University of Pittsburgh School of Medicine; and Weill Cornell Medical College have been collaborating on the National Institute of Mental Health Study of the Pharmacotherapy of Psychotic Depression trials, also known as STOP-PD I, and STOP-PD II, since 1999.

“On the one hand, discontinuing antipsychotic medication runs the risk of relapse for a severe life-threatening disorder,” Rothschild said. “On the other hand, continuing it unnecessarily exposes a patient to serious side effects, including weight gain and high cholesterol.”

A Phase I trial had found that the antipsychotic olanzapine plus the antidepressant sertraline were more effective than olanzapine plus placebo, but that both treatments were associated with an increase in weight and lipids over the 12-week study. The primary goal of the Phase II trial was to assess the risks and benefits of continuing antipsychotic medication once the depressive episode had responded to treatment with sertraline plus olanzapine.

In this 36-week randomized clinical trial that included 126 participants, 20 percent of trial participants randomized to sertraline plus olanzapine and 54 percent of participants randomized to sertraline plus placebo experienced a relapse after 36 weeks, a statistically significant difference.

“In patients with psychotic depression that had responded to the combination of sertraline and olanzapine, discontinuation of olanzapine was associated with a high risk of relapse despite continuation of the antidepressant, but continuation of the antipsychotic was associated with ongoing weight gain,” said Rothschild. “It is gratifying to have JAMA publish our study of this serious, but treatable, psychiatric disorder. Our future research will explore in more detail the optimal duration of treatment with olanzapine following remission of psychotic depression.”

Read the full JAMA article here.