Clinical Summary
Clinical Summary: Brexpiprazole in Combination With Sertraline and as Monotherapy in Posttraumatic Stress Disorder: A Full-Factorial Randomized Clinical Trial
PTSD remains chronic and disabling for many patients, and US Food and Drug Administration-approved pharmacologic options are limited to sertraline and paroxetine. In this trial, the clinically relevant question was whether adding brexpiprazole to sertraline improves PTSD symptoms beyond either agent alone.
Design
a Phase 2, multicenter, 12-week, randomized, double-blind, placebo- and active-controlled, parallel-arm trial
N
321 entered Period B and were randomized
Population
adults with PTSD
Duration
12-week, randomized, double-blind, placebo- and active-controlled, parallel-arm trial
Key Findings
- Brexpiprazole + sertraline improved CAPS-5 total score at Week 10 versus placebo + placebo, with a treatment difference of −5.99 (95% CI, −9.79 to −2.19; P=.0021).
- Brexpiprazole + sertraline improved CAPS-5 total score at Week 10 versus sertraline + placebo, with a treatment difference of −5.08 (95% CI, −8.96 to −1.20; P=.011).
- Brexpiprazole + sertraline improved CAPS-5 total score at Week 10 versus brexpiprazole + placebo, with a treatment difference of −4.24 (95% CI, −8.26 to −0.23; P=.038).
- Neither monotherapy separated from placebo at Week 10: brexpiprazole + placebo versus placebo + placebo had a treatment difference of −1.74 (95% CI, −5.70 to 2.22; P=.39), and sertraline + placebo versus placebo + placebo had a treatment difference of −0.91 (95% CI, −4.74 to 2.92; P=.64).
- Postrandomization, TEAEs were reported by 230/316 (72.8%) participants overall; mean change in body weight from randomization (Week 1) to each participant’s last visit was +1.4 kg for brexpiprazole+sertraline, and extrapyramidal symptom-related TEAEs occurred in 13 (16.3%) participants on brexpiprazole + sertraline.
Clinical Bottom Line
Brexpiprazole added to sertraline improved PTSD symptoms at Week 10, while brexpiprazole monotherapy and sertraline monotherapy did not separate from placebo in this trial. For adults with PTSD matching this study population, the efficacy signal was specific to the combination, with no new safety signals identified.
Practice Implications
- If considering brexpiprazole for PTSD, use it as combination treatment with sertraline rather than as monotherapy, since only brexpiprazole + sertraline showed significant CAPS-5 benefit at Week 10.
- Monitor weight and extrapyramidal symptoms during brexpiprazole + sertraline treatment: mean weight change was +1.4 kg, weight gain ≥7% occurred in 4/80 (5.0%), and extrapyramidal symptom-related TEAEs were reported in 13 (16.3%) participants.
- Discuss with patients that symptom separation from comparator groups emerged from Week 6 onwards, not immediately, when setting expectations for response.
- Apply these results cautiously outside the trial population, which excluded patients with a current DSM-5 major depressive episode, current or recent (within 120 days of screening) DSM 5 substance/alcohol use disorder, psychotropic-treatment resistant/refractory history in the investigator’s opinion, and those currently receiving sertraline with adequate dose and duration.
