FDA Panel Rejects Otsuka’s PTSD Drug Combo with Zoloft

A U.S. Food and Drug Administration (FDA) advisory panel has voted overwhelmingly against the approval of Otsuka Pharmaceutical's antipsychotic drug, brexpiprazole (Rexulti), in combination with Viatris’ antidepressant Zoloft (sertraline) for treating post-traumatic stress disorder (PTSD) in adults.

In a 10-1 vote on Friday, the panel concluded that existing clinical data failed to demonstrate the combination’s efficacy in reducing PTSD symptoms. The decision aligns with FDA staff reviewers’ earlier recommendation.

Otsuka’s application relied on one mid-stage and two late-stage clinical trials comparing the drug combo to sertraline plus placebo. One of the key phase 3 trials did not meet its primary endpoint, weakening the case for approval. Panel members emphasized the need for consistent positive data, especially when considering the long-term risks associated with antipsychotics, such as weight gain and movement disorders.

“We simply cannot negate one negative study and say we are going to approve based on two other positive studies,” said Pamela Shaw, a biostatistician at Kaiser Permanente. Another panelist, Walter Dunn of UCLA, raised concerns over the modest benefits compared to potential side effects of long-term antipsychotic use.

PTSD affects roughly 4% of U.S. adults and is commonly linked to war veterans, but can also be triggered by trauma such as abuse or natural disasters. If approved, the drug combo would have marked the first new PTSD treatment in over 20 years since the approval of Zoloft and Paxil.

Otsuka, which co-developed Rexulti with Denmark’s Lundbeck, said it will continue to work with the FDA during the ongoing review. The agency has not announced a new decision date. While the FDA often follows advisory panel recommendations, it is not obligated to do so.