he U.S. Food and Drug Administration (FDA) staff reviewers have raised significant concerns about the clinical efficacy of Otsuka Pharmaceutical’s proposed combination therapy for post‑traumatic stress disorder (PTSD), which pairs brexpiprazole (Rexulti) with Viatris’ sertraline (Zoloft).
These efficacy doubts surfaced ahead of an upcoming meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee, set for Friday, where independent experts will advise on whether the evidence supports regulatory approval
According to FDA briefing documents, the application is supported by data from one mid‑stage (phase II) and two late‑stage (phase III) clinical trials.
However, reviewers noted that one of the phase III studies failed to demonstrate statistically significant improvements in PTSD symptom reduction compared to sertraline monotherapy. Additionally, the phase II trial exhibited methodological limitations and raised questions about the reliability of its findings
Brexpiprazole, marketed under the brand name Rexulti, is already approved in the United States for treating agitation associated with Alzheimer’s disease, as well as for major depressive disorder and schizophrenia. Its proposed new indication would mark a substantial expansion into anxiety‑related conditions
PTSD affects approximately 4% of U.S. adults and is characterized by persistent symptoms such as intrusive flashbacks, nightmares, avoidance behavior, and severe anxiety following a traumatic event . Despite advances in psychopharmacology, no new PTSD medication has been approved in over three decades.
Originally slated for an FDA decision by February 8, 2025, Otsuka’s application was put on hold to allow advisory panel input on unresolved efficacy questions. The agency has not yet announced a revised action date.
If ultimately approved, this combination would become the first novel PTSD treatment in the U.S. since sertraline (Zoloft) and paroxetine (Paxil) earned approval in the early 1990s.
