Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans: A Randomized Clinical Trial

Abstract

Importance: Posttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness.

Objective: To compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans.

Design, setting, and participants: This randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021.

Interventions: Participants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions.

Main outcomes and measures: The primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life.

Results: Analyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21-80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1-40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5-41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89-1.08]) and CPT (SMD, 0.71 [95% CI, 0.61-0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53-4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00-1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12-1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24-2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events.

Conclusions and relevance: This randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment.

Trial registration: ClinicalTrials.gov Identifier: NCT01928732.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Schnurr reported receiving grants from the Department of Veterans Affairs (VA), Department of Defense (DoD), National Institute of Mental Health (NIMH), and Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work. Dr Chard reported grants receiving from Cincinnati VA Medical Center Chris T. Sullivan Foundation, DoD, and royalties from Guilford Publications. Dr Ruzek reported receiving personal fees from the National Institute for Human Resilience, Canadian Red Cross, Institute of Psychology at the Chinese Academy of Sciences, and University of Washington. Dr Resick reported receiving grants from NIMH, personal fees from DoD Office of Victims of Crime at the Medical University of South Carolina, and royalties from Guilford. Dr Foa reported receiving personal fees from PTSD workshops and royalties from Oxford University Press outside the submitted work. Dr Marx reported receiving grants from the VA, PCORI, NIMH, Military Suicide Research Consortium, and DoD and personal fees from American Psychological Association outside the submitted work. Dr Bovin reported receiving grants from the VA and personal fees from Premier Research outside the submitted work. Dr Astin reported grants from Collective Studies Program paid for study coordinator and supplies only during the conduct of the study. Dr Collie reported serving on the Advisory Steering Committee for the American Psychological Association’s Clinical Practice Guidelines. Dr Franklin reported receiving personal fees from New Harbinger Publications Royalties and grants from Patient-Centered Outcomes Research Institute outside the submitted work. Dr Davis reported receiving personal fees from Otsuka, Lundbeck, Janssen, and Signant Health and grants from Tonix, Alkermes, Allergan, Aptinyx, VA, DoD, Substance Abuse and Mental Health Services Administration, Social Finance, and Westat. No other disclosures were reported.

Figures

Figure.. Participant Recruitment Flowchart

aParticipants may have multiple reasons for exclusion. bOne ineligible patient was randomized and met the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) cutoff score but did not meet on Criterion E. One patient who was randomized to cognitive processing therapy (CPT) inadvertently received prolong exposure (PE), and 1 patient who was randomized to PE received CPT owing to staff error. cCompletion according to study protocol could be between 10 and 14 sessions; the number of sessions could be flexed according to patient need.