Lack of Generalizability of PTSD Treatment Trials: The Recent Brexpiprazole-Sertraline Trials as an Example

Background: Two recent studies demonstrated that brexpiprazole combined with sertraline was effective in reducing posttraumatic stress disorder (PTSD) symptoms, and an application has been submitted to the FDA for the combination treatment. When reading the inclusion and exclusion criteria of these studies, we suspected that many patients that we treat in our clinical practice would not have been eligible for the studies establishing the efficacy of the brexpiprazole-sertraline combination. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we estimated how many patients with PTSD in our practice would have qualified for the brexpiprazole-sertraline trials.

Methods: The sample was derived from the 3,800 psychiatric outpatients evaluated with semistructured diagnostic interviews, 417 of whom met DSM-IV criteria for PTSD upon presentation. The clinical protocol of the brexpiprazole-sertraline study listed the exclusion criteria. There were 11 exclusion criteria related to the patients' trauma history or psychiatric condition, almost all of which we assessed and applied to the sample.

Results: Three exclusion criteria were met by the majority of the patients: current major depressive disorder, PTSD age of onset before 16 years, and the interval between the onset of PTSD and patients' current age was 10 years or greater. Nearly 95% of patients met at least 1 of the exclusion criteria used in the brexpiprazole-sertraline studies.

Conclusions: While the effectiveness of the brexpiprazole-sertraline combination offers hope for addressing a significant unmet need in the treatment of PTSD, it is concerning that so few of our patients would have qualified for the clinical trials. As a result, we remain uncertain about the medications' effectiveness for most patients treated in clinical practice. We urge regulatory agencies to require industry to conduct studies that better reflect the patient populations seen in clinical practice.