Brexpiprazole and Sertraline Combination Significantly Improves PTSD Symptoms

Combining brexpiprazole and sertraline results in a statistically significant improvement in posttraumatic stress disorder (PTSD) symptoms compared to sertraline alone, according to a phase 3 randomized clinical trial published in JAMA Psychiatry.

Currently, the only FDA-approved pharmacotherapies for PTSD are selective serotonin reuptake inhibitors (SSRIs), including sertraline and paroxetine. However, nearly half of patients do not adequately respond to these treatments. To that aim, researchers in the current study aimed to evaluate the efficacy, safety, and tolerability of brexpiprazole in combination with sertraline compared to sertraline paired with a placebo.

Conducted at 86 clinical sites across the U.S. from October 2019 to August 2023, the double-blind, randomized, parallel-design trial involved adult outpatients diagnosed with PTSD. Participants were randomly assigned in a 1:1 ratio to receive either brexpiprazole (flexibly dosed at 2 to 3 mg daily) in combination with sertraline (fixed at 150 mg daily) or sertraline plus placebo over 11 weeks, after a 1-week, double-blind placebo run-in period implemented to reduce potential bias in efficacy outcomes. PTSD symptoms were assessed using the CAPS-5 structured interview while safety was assessed through a variety of measures.

The final study sample included 416 adult patients. At week 10, the brexpiprazole plus sertraline group showed a mean reduction in CAPS-5 scores of 19.2 points, compared to a 13.6-point reduction in the sertraline plus placebo group. This difference, which emerged as statistically significant by week 6 and was maintained through the trial duration, was accompanied by significant improvements across all key secondary outcomes, including global severity of illness and psychosocial functioning.

Moreover, 68.5% of participants receiving the combination therapy achieved a clinically meaningful 30% or greater reduction in PTSD symptoms, compared to 48.2% in the placebo group. Brexpiprazole plus sertraline was also notably effective in reducing depressive and anxiety symptoms associated with PTSD.

The safety profile of the combination therapy demonstrated good overall tolerability. Treatment-emergent adverse events were generally mild or moderate, with nausea being the most common, affecting approximately 12% in both treatment groups. Weight gain, fatigue, and somnolence were slightly more frequent with the combination therapy, but discontinuation due to adverse effects was notably lower (3.9%) compared to sertraline plus placebo (10.2%).

Study limitations included stringent inclusion and exclusion criteria as well as an exclusive focus on US clinical sites and short-term efficacy.

The study authors concluded, “Brexpiprazole + sertraline demonstrated efficacy on overall PTSD symptoms and on each of the 4 PTSD symptom clusters compared with treatment with sertraline + placebo. Brexpiprazole + sertraline was also associated with improvements in depression, anxiety, and psychosocial functioning.”

Disclosure: This study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S, the co-developers of brexpiprazole. Several authors reported employment or advisory roles with Otsuka and Lundbeck.

This article originally appeared on Psychiatry Advisor