A comparison of prolonged exposure therapy, pharmacotherapy, and their combination for PTSD: What works best and for whom; study protocol for a randomized trial.

Background: Several efficacious psychological and pharmacological treatments for posttraumatic stress disorder (PTSD) are available; however, the comparative effectiveness of these treatments represents a major gap in the literature. The proposed study will compare the effectiveness of two leading PTSD treatments - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine extended release - as well as the combination of PE and medication.

Methods: In a randomized clinical trial, veterans with PTSD (N = 450) recruited across six Veterans Affairs Medical Centers will complete assessments at baseline, mid-treatment (Week 7), post-treatment (Week 14), and follow-up (Weeks 27 and 40). The primary outcome will be change in (both clinician-rated and self-reported) PTSD severity. Depression symptoms, quality of life, and functioning will also be measured and examined as secondary outcomes. Baseline demographic and clinical data will be used to develop "personalized advantage indices" (PAIs), with the goal of identifying who is most likely to benefit from which treatment.

Conclusions: This planned trial will yield findings to directly inform clinical practice guidelines for PTSD, by providing comparative effectiveness data to support recommendations about what can be considered the "first-line" treatment option(s) for PTSD. Further, findings from this trial have the potential to guide treatment planning for individual patients, through implementation of PAIs developed from study data, in service of "personalized medicine."

Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04961190.