Psychiatric Times Experts Weight in on FDA Advisory Decision for PTSD

With the US Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee voting 10 to 1 against recommending approval of brexpiprazole (Rexulti) adjunctive to sertraline for adults with posttraumatic stress disorder (PTSD), clinicians are left to ponder what comes next for their patients.

In a Psychiatric Times Drug Watch Special Report, Editor in Chief John J. Miller, MD, spoke with Michael Asbach, DMSc, PA-C, Psych-CAQ, and Erin Crown, MHS, PA-C, Psych-CAQ, about their reactions and the implications for practice.

“We saw some of the documents and some of the signals coming out a couple days ahead of this meeting,” Asbach said, noting he was not too surprised. Still, he acknowledged the unmet need in PTSD. “PTSD is an incredibly difficult condition. We don't have a whole lot of options in terms of pharmacotherapy, and we desperately need new innovation in the space,” he added. “But at the same time, we want to make sure that we meet the evidentiary standard. We have those standards in place for a reason, and there were some concerns with some of the studies.”

Crown was struck by the vote margin. “I'm surprised that it was that significantly opposed,” she told her colleagues. She underscored the burden outside military settings. “PTSD is such a prevalent condition, not only amongst veterans, but it’s actually prevalent at a much higher rate amongst the civilian population,” she added.

“This places prescribers in a unique and difficult position,” Miller pointed out to his colleagues. “What do we do? How do we access these treatments if we think that they would be of benefit?”

Off-label use will remain part of care, Asbach noted, saying it is too simplistic to think otherwise. “. If we think about prescribing as a world where if it is on label, people will use it, and if it's off label or not approved, then we'll just tell our patients, ‘Sorry.’ There's nothing else I can do,’” he said. “But that's not the reality of what happens in clinic. Very often we prescribe off label, and I think a lot of times we hold meds to unfair standards, where, when we prescribe something off label, we're often doing so hopefully with some level of evidence to support it, but that level of evidence may be of lower quality, certainly not too large, randomized control trials.”

“I think this is the toughest thing with these FDA boards,” he added. “Certainly we need to meet the evidentiary standard. And if we want to have a conversation about whether we need 2 positive studies or maybe that should only be 1, we can certainly do that. But the flip side to that is there's a really important role of demonstrating safety, because a lot of times meds, as they're studied for approval in terms of efficacy, end up being very different in the real world when we use them… There's a lot of nuance here, because the role of the FDA is something that I think can be open for debate, whether it truly should be focused on efficacy safety, or one should be prioritized over the other.”

On the positive side, Asbach was pleased to see with the risk-benefit analysis and data. “The safety profile looks quite good, and no new safety signals were identified…That gives me a lot of confidence…because a lot of the alternatives…have far less evidence.”

Based on the evidence and vote, it is unlikely the FDA will approve the sNDA, which leaves clinicians and their patients in the same challenging situation. With that in mind, Crown has a challenge for the field and poses the question: “What can we do from a scientific standpoint, to better understand the condition and therefore potentially better understand how we might be able to demonstrate more effective treatment down the road?”