Brexpiprazole and Sertraline Combination Therapy Shows Efficacy in Treating PTSD

Brexpiprazole in combination with sertraline resulted in statistically significantly greater improvement of posttraumatic stress disorder (PTSD) symptoms compared to treatment with sertraline plus placebo, according to new data published in JAMA Psychiatry.1

“About 6% of the United States population will have PTSD at some point in their lives, but around only half will seek treatment,” Lori Davis, MD, clinical professor of psychiatry in the Department of Psychiatry and Behavioral Neurobiology, University of Alabama School of Medicine, who served as lead author on study, said in a joint press release from Otsuka and Lundbeck.2 “The Phase 3 results are an important and encouraging step forward in the hopes of providing PTSD patients with a new therapeutic option in the future.”

Davis and colleagues conducted the parallel-design, double-blind, randomized clinical trial from October 2019 to August 2023 to examine the efficacy, safety, and tolerability of brexpiprazole in combination with sertraline for the treatment of PTSD. A total of 416 individuals with PTSD were enrolled in the study and randomly assigned to receive either brexpiprazole (2-3 mg/day) with sertraline (150 mg/day) or sertraline (150 mg/day) with a placebo. The primary endpoint was the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (week 1) to week 10.1

Results indicated that the combination therapy significantly reduced PTSD symptoms compared to the placebo group. The CAPS-5 scores demonstrated a clinically meaningful improvement, suggesting that this dual approach may enhance treatment outcomes for patients who have not responded adequately to standard therapies.1

In addition to PTSD symptom assessment, the study evaluated secondary endpoints, including overall functioning and quality of life, using tools such as the Brief Inventory of Psychosocial Function (B-IPF) and the 36-item Short-Form Health Survey (SF-36v2). These measures highlighted improvements in both physical and mental health domains among participants receiving the combination treatment.1

The safety profile of brexpiprazole in combination with sertraline was consistent with that of brexpiprazole in approved indications.1

“The outcome of this trial provides us with an opportunity to help patients with PTSD,” Johan Luthman, executive vice president and head of Research & Development at Lundbeck, said in the press release.2 “With these promising results, we are committed to working closely with the FDA to help bring brexpiprazole in combination with sertraline to the healthcare professionals serving the PTSD patient community.”

References:

1. Davis LL, Behl S, Lee D, et al. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. JAMA Psychiatry. Published online December 18, 2024. doi:10.1001/jamapsychiatry.2024.3996

2. JAMA Psychiatry Publishes Results of Otsuka and Lundbeck's Phase 3 Trial of Brexpiprazole in Combination with Sertraline in Treatment of Post-Traumatic Stress Disorder (PTSD) in Adults. News release. Otsuka, Lundbeck. December 18, 2024. Accessed December 18, 2024. https://www.businesswire.com/news/home/20241218951537/en/JAMA-Psychiatry-Publishes-Results-of-Otsuka-and-Lundbecks-Phase-3-Trial-of-Brexpiprazole-in-Combination-with-Sertraline-in-Treatment-of-Post-Traumatic-Stress-Disorder-PTSD-in-Adults