FDA's Negative Vote on Brexpiprazole for PTSD: What's Next?

Following the recent US Food and Drug Administration Advisory Committee meeting, Psychiatric Times sat down with editorial board member Gus Alva, MD, Medical Director of ATP Clinical Research, to unpack the 10–1 vote against recommending brexpiprazole (Rexulti) in combination with sertraline for posttraumatic stress disorder (PTSD). Alva discussed the implications for clinical practice, the gaps in available therapies, and the hope that continues to drive innovation. (Please see insights from editor in chief John J. Miller, MD, and colleagues directly following the meeting.)

“10 to 1 is probably the worst potential outcome,” Alva told Psychiatric Times. “It’s disappointing. We obviously saw an MDMA-geared therapy shot down in a very similar manner.” The advisory committee’s vote reflects concerns about the mixed data package, which included two phase 3 trials—study 71, which was positive, and study 72, which was negative—along with additional analyses from a phase 2 study. “The perception was that maybe had the original way of running that phase two trial been done, it would have been found to be a negative,” Alva explained. “That drove the rhetoric for the advisory group to basically say that the data was not necessarily compelling in a sufficient manner.”

The decision underscores the longstanding challenge of developing new pharmacologic treatments for PTSD, a condition that affects approximately 4% of individuals and has seen few therapeutic advancements in decades. “We haven't had a new treatment for PTSD in over quarter of a century,” Alva added. “It’s critical that we have other therapies out there beyond the classic SSRIs that we've known and had for 30 plus years.”

Although the FDA has yet to issue its final decision, Alva noted that a new trial may be requested, which would extend timelines and add significant costs, something the sponsors may not be able to do. “As things stand now, probably what's going to come out of this is the FDA maybe coming back to the sponsors, meaning Otsuka and Lundbeck, and probably suggesting another trial to be done,” he said.

Despite the setback, Alva, who recently hosted the 2025 Southern Psychiatry Conference highlighting new research, remains optimistic about the future of new medications in psychiatry. "The beauty is that we are in a space which is fluid. There's a continuation of innovation, and we've certainly seen an abundance of different candidates of medications with different modes of action that are earmarked towards affective conditions," he said. "I do feel very confident that with the continued work, the zeal, the effort that's being driven in this particular field of medicine, we're going to be coming across maybe better treatment modalities to offer our patients."

With the FDA yet to make its final decision, Psychiatric Times will continue to follow the story and the broader treatment pipeline, bringing clinicians the latest insights and expert analysis.