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Randomized Controlled Trial
. 2019 Feb 1;76(2):117-126.
doi: 10.1001/jamapsychiatry.2018.3412.

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

Sheila A M Rauch  1   2 , H Myra Kim  1   3 , Corey Powell  3 , Peter W Tuerk  4   5 , Naomi M Simon  6   7 , Ron Acierno  4   8 , Carolyn B Allard  9   10 , Sonya B Norman  9   10   11 , Margaret R Venners  1 , Barbara O Rothbaum  2 , Murray B Stein  9   10 , Katherine Porter  1   12 , Brian Martis  9   10 , Anthony P King  1   12 , Israel Liberzon  1   12 , K Luan Phan  13   14 , Charles W Hoge  15
Affiliations
Randomized Controlled Trial

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

Sheila A M Rauch et al. JAMA Psychiatry. .

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.

Trial registration: ClinicalTrials.gov Identifier: NCT01524133.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rauch reported receiving support from the Wounded Warrior Project, Department of Veterans Affairs, National Institutes of Health, Woodruff Foundation, and Department of Defense; and receiving royalties from Oxford University Press. Dr Simon reported receiving funding from the American Foundation for Suicide Prevention, Department of Defense, Highland Street Foundation, National Institutes of Health, and Janssen; serving as a speaker for Massachusetts General Hospital Psychiatry Academy, Axovant Sciences, and Springworks Therapeutics; and that her spouse has an equity stake in G1 Therapeutics. Dr Rothbaum reported receiving funding from the Wounded Warrior Project, Department of Defense Clinical Trial grant W81XWH-10-1-1045, National Institute of Mental Health grant 1R01MH094757-01, and the McCormick Foundation. Dr Rothbaum reported receiving royalties from Oxford University Press, Guilford, American Psychiatric Publishing, Inc, and Emory University and receiving one advisory board payment from Genentech, Jazz Pharmaceuticals, and Aptinyx. Dr Stein reported in the past 3 years serving as a consultant for Actelion, Alkermes, Aptinyx, Bionomics, Dart Neuroscience, Healthcare Management Technologies, Janssen, Neurocrine Biosciences, Oxeia Biopharmaceuticals, Pfizer, and Resilience Therapeutics; owning founders shares and stock options in Resilience Therapeutics; and having stock options in Oxeia Biopharmaceticals. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram of Participants in the Prolonged Exposure and Sertraline Trial
CAPS indicates Clinician Administered PTSD Scale; ITT, intent to treat; LTF, lost to follow-up; MGH, Massachusetts General Hospital Home Base Veterans Program; PE, prolonged exposure therapy; PI, principal investigator; PTSD, posttraumatic stress disorder; RHJVAMC, Ralph H. Johnson Veterans Affairs Medical Center; VAAAHS, Veterans Affairs Ann Arbor Healthcare System; and VASDHS, Veterans Affairs San Diego Healthcare System. aSome individuals had more than 1 exclusion. bGroups not mutually exclusive.
Figure 2.
Figure 2.. Cross-sectional Mean Scores of Clinician-Administered PTSD Scale (CAPS) Showing Change in Posttraumatic Stress Disorder Symptoms During Treatment
PE indicates prolonged exposure therapy; PLB, placebo; PTSD, posttraumatic stress disorder; and SERT, sertraline hydrochloride. Error bars represent 95% CIs.
See this image and copyright information in PMC

Comment in

References

    1. US Department of Veterans Affairs Management of posttraumatic stress disorder and acute stress reaction 2017. https://www.healthquality.va.gov/guidelines/mh/ptsd/. Updated August 29, 2018. Accessed October 26, 2018.
    1. Institute of Medicine Treatment of PTSD: an assessment of the evidence, report brief. Washington, DC: Institute of Medicine; 2007.
    1. Forbes D, Creamer M, Bisson JI, et al. . A guide to guidelines for the treatment of PTSD and related conditions. J Trauma Stress. 2010;23(5):537-552. doi:10.1002/jts.20565 - DOI - PubMed
    1. American Psychological Association Clinical practice guideline for the treatment of posttraumatic stress disorder (PTSD). https://www.apa.org/ptsd-guideline/. Accessed October 26, 2018.
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