Background: Participants are allowed to stay on their prescribed psychotropic medication in most trials examining psychological interventions for adult post-traumatic stress disorder (PTSD). Objectives: We aimed to conduct the first meta-analysis investigating the potential influence of such concurrent medication on efficacy. Method: To this end, we searched Medline, PsycINFO, Web of Science, and PTSDpubs from inception to April 21, 2022, for trials meeting the following criteria: (1) randomized controlled trial (RCT), (2) PTSD as primary treatment focus, (3) interview-based PTSD baseline rate ≥70%, (4) N ≥ 20, (5) mean age ≥18 years. Trials were excluded when intake of psychotropics was not (sufficiently) reported. Results: Most published trials did not report on the intake of psychotropic medication. A total of 75 RCTs (N = 4,901 patients) met inclusion criteria. Trauma-focused cognitive behavior therapy (TF-CBT) was the most well-researched intervention. Short-term efficacy of psychological treatments did not differ by the proportion of participants taking concurrent psychotropic medication during psychological treatment in all but one analysis. In trials comparing TF-CBT and active control conditions at posttreatment, TF-CBT was more effective when most participants were concurrently medicated (g = 0.87, 95% CI 0.53–1.22) rather than unmedicated (g = 0.27; 95% CI 0.01–0.54, p = 0.017), with younger age (b1 = −0.04, p = 0.008) and higher proportion of females (b1 = 0.01, p = 0.014) being associated with higher efficacy only in trials with high proportions of medicated participants. No differences in efficacy by proportions of participants taking concurrent psychotropic medication were found at follow-up. Conclusions: Results suggest that psychological interventions are effective for PTSD irrespective of concurrent intake of psychotropics.

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