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A groundbreaking medication combining brexpiprazole, an atypical antipsychotic, and sertraline, a selective serotonin reuptake inhibitor (SSRI), has demonstrated significant efficacy in alleviating symptoms of posttraumatic stress disorder (PTSD), according to results from a phase 3 clinical trial. If approved by the US Food and Drug Administration (FDA), this would mark the first new pharmacologic treatment for PTSD in over two decades.
The trial, funded by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, met its primary endpoint of improving scores on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) after 10 weeks, as well as secondary outcomes related to anxiety, depression, and psychosocial functioning.
Key Findings
The study enrolled 416 adults with moderate to severe PTSD symptoms persisting for at least six months. Participants were randomized to receive daily doses of brexpiprazole (2-3 mg) plus sertraline (150 mg) or sertraline with a placebo. By week 10, the brexpiprazole-sertraline group showed a greater reduction in CAPS-5 scores (-19.2 points) compared to the sertraline-placebo group (-13.6 points).
“What’s particularly impactful is the improvement in psychosocial functioning alongside symptom relief,” said Dr. Lori L. Davis, a senior research psychiatrist at Birmingham Veterans Affairs Health Care System and a lead investigator of the study. “This combination shows promise in not just treating PTSD symptoms but also helping patients regain their quality of life.”
Clinical Significance
The combination therapy also outperformed the placebo group on the Brief Inventory of Psychosocial Function, with significant improvements noted by week 12. Dr. Davis emphasized that such dual benefits—symptom reduction and enhanced functionality—underscore the clinical relevance of the findings.
Dr. John Krystal, a PTSD expert not involved in the study, called the results promising. “This addresses an urgent need for more effective PTSD treatments, especially given the limitations of current medications like sertraline and paroxetine,” said Dr. Krystal, who also chairs the psychiatry department at Yale University.
Safety Profile
The trial reported a favorable safety profile for the brexpiprazole-sertraline combination. Adverse events were infrequent, with nausea being the most common (12.2% for the combination group vs. 11.7% for the placebo group). Discontinuation due to adverse events was lower in the combination group (3.9%) compared to the placebo group (10.2%).
Some mild side effects included weight gain (1.3 kg average increase), fatigue, and somnolence, all of which were more prevalent in the combination group.
Regulatory Review and Future Research
The FDA is currently reviewing the supplemental new drug application, with a decision expected by February 2025. The findings are part of a larger clinical program that included three trials, two of which met their primary endpoints.
Experts caution that further studies are needed to assess long-term efficacy and safety, as well as the medication’s applicability to diverse populations, including military personnel and veterans who experience PTSD at higher rates.
“The results are promising, but it’s essential to explore subgroup responses and the potential for broader application,” said Dr. Vincent F. Capaldi, chair of psychiatry at the Uniformed Services University of the Health Sciences.
Implications for PTSD Treatment
If approved, the brexpiprazole-sertraline combination could fill a critical gap in PTSD care, providing new hope for the millions of people affected by this debilitating condition.
“This study represents a significant step forward,” Dr. Davis said. “The potential to improve not just symptoms but also the overall functioning of individuals with PTSD is a game-changer.”
