Efficacy of Prolonged Exposure Therapy, Sertraline Hydrochloride, and Their Combination Among Combat Veterans With Posttraumatic Stress Disorder : A Randomized Clinical Trial

Key Points

Question  How do prolonged exposure therapy, sertraline hydrochloride, and their combination compare with regard to reducing the severity of posttraumatic stress disorder symptoms during 24 weeks of treatment?

Findings  This randomized clinical trial showed that, in a modified intent-to-treat analysis (n = 207) using a mixed model of repeated measures, the severity of posttraumatic stress disorder symptoms decreased significantly during the 24 weeks of treatment; however, slopes did not differ by treatment arms and at 24 weeks.

Meaning  No difference in change in posttraumatic stress disorder symptoms or symptom severity at 24 weeks was found across the 3 groups of sertraline plus enhanced medication management, prolonged exposure plus placebo, and prolonged exposure plus sertraline.

Abstract

Importance  Meta-analyses of treatments for posttraumatic stress disorder (PTSD) suggest that trauma-focused psychotherapies produce greater benefits than antidepressant medications alone.

Objective  To determine the relative efficacy of prolonged exposure therapy plus placebo, prolonged exposure therapy plus sertraline hydrochloride, and sertraline plus enhanced medication management in the treatment of PTSD.

Design, Setting, and Participants  The Prolonged Exposure and Sertraline Trial was a randomized, multisite, 24-week clinical trial conducted at the Veterans Affairs Ann Arbor Healthcare System, Veterans Affairs San Diego Healthcare System, Ralph H. Johnson Veterans Affairs Medical Center, and Massachusetts General Hospital Home Base Veterans Program between January 26, 2012, and May 9, 2016. Participants and clinicians were blinded to pill condition, and outcome evaluators were blinded to assignment. Participants completed assessments at weeks 0 (intake), 6, 12, 24, and 52 (follow-up). Participants (N = 223) were service members or veterans of the Iraq and/or Afghanistan wars with combat-related PTSD and significant impairment (Clinician-Administered PTSD Scale score, ≥50) of at least 3 months’ duration. Analyses were on an intent-to-treat basis.

Intervention  Participants completed up to thirteen 90-minute sessions of prolonged exposure therapy by week 24. Sertraline dosage was titrated during a 10-week period and continued until week 24; medication management was manualized.

Main Outcomes and Measures  The primary outcome was symptom severity of PTSD in the past month as assessed by the Clinician-Administered PTSD Scale score at week 24.

Results  Of 223 randomized participants, 149 completed the study at 24 weeks, and 207 (180 men and 27 women; mean [SD] age, 34.5 [8.3 years]) were included in the intent-to-treat analysis. Modified intent-to-treat analysis using a mixed model of repeated measures showed that PTSD symptoms decreased significantly during the 24 weeks (sertraline plus enhanced medication management, 33.8 points; prolonged exposure therapy plus sertraline, 32.7 points; and prolonged exposure therapy plus placebo, 29.4 points; β,–9.39; 95% CI, −11.62 to −7.16; P < .001); however, slopes did not differ by treatment group (prolonged exposure therapy plus placebo group, –9.39; sertraline plus enhanced medication management group, –10.37; and prolonged exposure therapy plus sertraline group, –9.99; P = .81).

Conclusions and Relevance  No difference in change in PTSD symptoms or symptom severity at 24 weeks was found between sertraline plus enhanced medication management, prolonged exposure therapy plus placebo, and prolonged exposure therapy plus sertraline.