How to Select Adults With PTSD for Brexpiprazole Plus Sertraline
How do clinicians identify which adults with posttraumatic stress disorder are the best match for brexpiprazole plus sertraline based on this trial?
Adults with posttraumatic stress disorder often remain symptomatic despite limited medication options, but this trial’s efficacy signal was specific to brexpiprazole combined with sertraline rather than either drug alone. Clinicians considering this regimen need to know which patients resembled the study population and which common clinical scenarios were excluded.
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Confirm chronic DSM-5 PTSD with substantial baseline severity
Use a structured diagnostic approach consistent with DSM-5 PTSD and confirm that symptoms have been present for at least 6 months. In the trial, participants also had to have a CAPS-5 total score of at least 33 at both screening and baseline, so the evidence applies to adults with clearly symptomatic PTSD rather than milder presentations.
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Check that the patient resembles the outpatient study population
The trial enrolled outpatients aged 18 to 65 years. Apply the findings most directly to adults in this age range who are being managed in outpatient care, because that is the population studied.
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Exclude major conditions that would have made the patient ineligible
The study excluded patients with a current DSM-5 major depressive episode, a current or recent primary anxiety disorder that had been the focus of psychiatric treatment, current or recent substance or alcohol use disorder within 120 days of screening, significant suicide risk, prior brexpiprazole exposure, and psychotropic-treatment resistance or refractoriness by investigator history. It also excluded patients with a traumatic event within 3 months of screening, an index trauma before age 16, or an index trauma more than 15 years before screening.
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Review current treatment status before considering the combination
Do not generalize these results to patients already receiving sertraline with adequate dose and duration, because those patients were excluded. The trial also excluded patients with any change in PTSD treatment within 28 days of screening and required washout of prohibited psychotropic medications before randomization.
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Prefer the combination rather than either medication alone
If using brexpiprazole based on this study, pair it with sertraline rather than using brexpiprazole monotherapy. At Week 10, brexpiprazole plus sertraline improved CAPS-5 total score versus sertraline plus placebo by -5.08 points, versus brexpiprazole plus placebo by -4.24 points, and versus placebo plus placebo by -5.99 points, while neither monotherapy arm separated from placebo.
Clinical Considerations
- The study population excluded several common real-world PTSD scenarios, so generalizability is limited.
- The sertraline monotherapy arm did not separate from placebo, which the authors identified as a limitation for assay sensitivity.
- The trial excluded patients currently receiving adequate sertraline treatment, so the findings do not directly answer whether to add brexpiprazole after an adequate sertraline trial.
- The article states that results need replication, although it notes that a larger trial has recently provided further evidence.
Bottom Line
Use this evidence for adults with chronic, clinically significant outpatient PTSD who match the trial’s narrow eligibility profile, and choose brexpiprazole only in combination with sertraline because the efficacy signal was not seen with monotherapy.
