JAMA Psychiatry Reports Phase 3 Trial of Brexpiprazole with Sertraline for PTSD in Adults

A recent clinical trial has revealed promising results for the treatment of post-traumatic stress disorder (PTSD) in adults using a combination of brexpiprazole and sertraline. Conducted by Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck Pharmaceuticals LLC, the Phase 3 trial demonstrated a statistically significant improvement in PTSD symptoms when brexpiprazole was combined with sertraline, compared to the use of sertraline and a placebo. These findings were published in JAMA Psychiatry.

The trial, which was a double-blind, randomized study, involved 416 adult outpatients diagnosed with PTSD. Participants were divided into two groups: one received a daily dose of brexpiprazole (2-3 mg) along with sertraline (150 mg), while the other received sertraline (150 mg) and a placebo. The primary objective was to measure changes in PTSD symptoms using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from the start of the study (Week 1) to Week 10.

Results indicated a notable reduction in CAPS-5 scores for those on brexpiprazole and sertraline, with a mean decrease of 19.2 points, compared to a 13.6-point decrease in the placebo group. This represents a statistically significant difference, with the brexpiprazole group showing greater improvement in PTSD symptoms.

Secondary outcomes also demonstrated significant enhancements. The study assessed changes in the Clinical Global Impression-Severity of Illness score (CGI-S) from Week 1 to Week 10, and the Brief Inventory of Psychosocial Function (B-IPF) from Day 0 to Week 12, both showing favorable results for the brexpiprazole and sertraline combination.

In terms of safety, the combination of brexpiprazole and sertraline showed a profile consistent with brexpiprazole's approved uses. Adverse events led to discontinuation in 3.9% of participants taking brexpiprazole and sertraline, compared to 10.2% for those on sertraline and placebo. Common side effects in the brexpiprazole group included nausea (12.2%), fatigue (6.8%), weight gain (5.9%), and somnolence (5.4%).

PTSD is a prevalent mental health condition in the U.S., affecting millions annually. It arises from exposure to traumatic events and is characterized by symptoms such as intrusive memories, avoidance behaviors, negative emotional states, and heightened arousal. Despite its prevalence, treatment options remain limited, with many affected individuals not seeking help.

Brexpiprazole, approved by the FDA in 2015, has been used as an adjunctive therapy for major depressive disorder and for treating schizophrenia. Its mechanism involves modulation of serotonin and dopamine activity, with high affinity for certain norepinephrine and serotonin receptors. The recent study's findings suggest brexpiprazole, when used with sertraline, may offer a new therapeutic avenue for PTSD sufferers, providing meaningful symptom relief.

The application for a supplemental New Drug Application (sNDA) for brexpiprazole and sertraline in treating PTSD is currently under review by the FDA, with a decision expected by early 2025. If approved, this combination could become an important option for clinicians treating PTSD, offering hope to patients seeking effective management of their symptoms.

The trial and its positive outcomes underscore the potential for brexpiprazole in combination with sertraline to address the unmet needs of PTSD patients, highlighting the ongoing efforts to expand therapeutic strategies for this challenging condition.