Recent clinical trials have investigated the efficacy of brexpiprazole (Rexulti) in combination with sertraline for treating post-traumatic stress disorder (PTSD). This combination has shown promise in reducing PTSD symptoms, though results have varied across studies.
Clinical Trial Findings:
- Phase 3 Trial (NCT04124614): This randomized, double-blind study evaluated brexpiprazole (2–3 mg/day) combined with sertraline (150 mg/day) versus sertraline with placebo over 11 weeks. The combination group demonstrated a statistically significant greater reduction in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), compared to the sertraline plus placebo group .
- Phase 2 Trial (NCT03033069): This study assessed brexpiprazole both as monotherapy and in combination with sertraline. The combination therapy showed significant improvement in PTSD symptoms compared to placebo, whereas brexpiprazole monotherapy did not demonstrate a significant effect .
- Phase 3 Trial (NCT04174170): This trial tested fixed doses of brexpiprazole (2 mg/day and 3 mg/day) with sertraline. While the primary endpoint was not met, reductions in PTSD symptom severity were observed, aligning with findings from the other trials .
Safety and Tolerability:
Across these studies, the brexpiprazole and sertraline combination was generally well-tolerated. Common side effects included nausea, fatigue, weight gain, and somnolence. The incidence of treatment-emergent adverse events was comparable between the combination therapy and sertraline plus placebo groups .
Regulatory Status:
Based on these findings, a supplemental new drug application (sNDA) was submitted to the U.S. Food and Drug Administration (FDA) in April 2024 for the approval of brexpiprazole in combination with sertraline for the treatment of PTSD in adults. The FDA’s decision is pending .
Conclusion:
The combination of brexpiprazole and sertraline has shown potential in alleviating PTSD symptoms, particularly in patients who may not respond adequately to standard treatments. However, further research and regulatory review are necessary to fully establish its efficacy and safety profile for this indication.
