Brexpiprazole in Combination With Sertraline and as Monotherapy in Posttraumatic Stress Disorder: A Full-Factorial Randomized Clinical Trial

Objective: To investigate the efficacy, safety, and tolerability of brexpiprazole in combination with sertraline and as monotherapy for posttraumatic stress disorder (PTSD). Methods: The trial comprised a 1-week placebo run-in period followed by an 11-week, randomized, double-blind, active-referenced, placebo-controlled, parallel-arm treatment period (with 14-day follow-up). The trial ran from January 2017 -November 2018 at 48 clinical trial sites in the United States. Adult outpatients with PTSD (DSM-5) were randomized (1:1:1:1) to oral brexpiprazole +sertraline, brexpiprazole + placebo, sertraline+ placebo, or placebo+ placebo. Doses were flexible (brexpiprazole 1-3 mg/d; sertraline 100-200 mg/d). The primary endpoint was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (Week 1) to Week 10. Safety assessments included adverse events. Results: Among 321 randomized participants, completion rates were 58/82 (70.7%) for brexpiprazole +sertraline, 50/75 (66.7%) for brexpiprazole + placebo, 59/81 (72.8%) for sertraline + placebo, and 64/83 (77.1%) for placebo+ placebo. At Week 10, brexpiprazole +sertraline demonstrated greater improvement in CAPS-5 total score (randomization, 35.7; least-squares [LS] mean change, -16.4; n=77) vs sertraline+ placebo (randomization, 36.5; LS mean change, -11.4; n =75) with LS mean difference,-5.08 (95% CI,-8.96 to-1.20; P=.011), and also vs brexpiprazole+ placebo and vs placebo + placebo. Brexpiprazole + placebo and sertraline + placebo did not differ from placebo + placebo. Treatment- emergent adverse events with incidence >= 10% were weight increased (12.5%) and somnolence (10.0%) for brexpiprazole +sertraline, akathisia (13.3%) for brexpiprazole + placebo, and nausea (20.3%) and dry mouth (12.7%) for sertraline+ placebo. Conclusions: Brexpiprazole in combination with sertraline (but not as monotherapy) has potential to be a new efficacious treatment for PTSD, with a safety profile consistent with brexpiprazole in approved indications.