Key Takeaways
Extended Takeaways
- The efficacy signal was specific to the combination arm: brexpiprazole + sertraline improved CAPS-5 total score at Week 10 versus brexpiprazole + placebo by −4.24 (95% CI, −8.26 to −0.23; P=.038) and versus placebo + placebo by −5.99 (95% CI, −9.79 to −2.19; P=.0021), while neither monotherapy arm separated from placebo.
- Symptom improvement with brexpiprazole + sertraline emerged by Week 6 and was seen across multiple domains at Week 10, including CAPS-5 Intrusion, Avoidance, and Negative cognitions and mood clusters, plus CGI-S, PCL-5, HADS Anxiety, and HADS Depression.
- A substantial placebo run-in effect was present before randomization, with a mean (SD) CAPS-5 total score change of −7.7 (9.3) points from baseline (Day 0) to Week 1; subgroup analyses also suggested larger Week 10 treatment differences among placebo run-in nonresponders.
- The study population excluded several common clinical scenarios, including current major depressive episode, recent substance/alcohol use disorder, psychotropic-treatment resistance/refractoriness by investigator history, recent treatment changes, and current adequate sertraline treatment, so generalizability to broader PTSD practice may be limited.
- Tolerability was acceptable, but clinicians should monitor weight and akathisia when using brexpiprazole in PTSD: mean weight change was +1.4 kg with brexpiprazole + sertraline, weight gain ≥7% occurred in 4/80 (5.0%), and extrapyramidal symptom-related TEAEs were reported in 13 (16.3%) participants, although SAS, AIMS, and BARS changes were minimal.
- Suicidality findings did not show a clear excess with the combination arm in this small trial: C-SSRS treatment-emergent suicidal ideation occurred in 4/80 (5.0%) on brexpiprazole + sertraline versus 9/79 (11.4%) on sertraline + placebo and 8/82 (9.8%) on placebo + placebo, with 1 suicide attempt in the combination group and 1 treatment-emergent suicidal behavior event on sertraline + placebo.
