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Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder

An Update of the PTSD-Repository Evidence Base

Systematic Review

This report is available in PDF and XLSX only (Systematic Review [PDF, 1.6 MB], Evidence Summary [PDF, 277.4 KB]; Appendix Table E [XLSX, 420.7 KB], Appendix Table F-1 [XLSX, 42.1 KB], Appendix Table G-1 [XLSX, 16.3 KB]). For additional assistance, please contact us.

Main Points

  • This update adds newly published studies on posttraumatic stress disorder (PTSD, 47 randomized controlled trials [RCTs]), studies targeting comorbid PTSD and substance use disorders (SUDs, 21 RCTs), and variables related to comorbidities such as SUDs and suicidal ideation/behavior, to the PTSD-Repository, a database of RCTs of interventions to treat PTSD.
  • We abstracted data from 389 RCTs, which included psychotherapeutic interventions (63%), pharmacologic interventions (25%), and complementary and integrative or nonpharmacologic biological treatments (12%).
  • Reporting was incomplete for many data elements in published studies: less than half of studies reported on the loss of PTSD diagnosis (i.e., no longer meeting criteria for PTSD) or clinically meaningful response/remission of symptoms.
  • Risk of bias (ROB) was assessed for all included studies; most were rated as having a medium ROB (57%), and only 6 percent were rated as having a low ROB.
  • An exploration of an expanded ROB system was developed and pilot tested.

Structured Abstract

Objectives. Identify and abstract data from posttraumatic stress disorder (PTSD) treatment randomized controlled trials (RCTs) to update the PTSD Trials Standardized Data Repository (PTSD-Repository) with data on PTSD and mental health, including suicide-related outcomes and substance use.

Data sources. We searched PTSDpubs, Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs published from 1980 to May 22, 2020.

Review methods. In consultation with the National Center for PTSD (NCPTSD), we updated the PTSD-Repository by expanding inclusion criteria to RCTs targeting comorbid PTSD/substance use disorder (SUD) and adding data elements. The primary publication for each RCT was abstracted; data and citations from secondary publications (i.e., companion papers) appear in the same record. We assessed risk of bias (ROB) for all studies in the PTSD-Repository. We undertook an exploratory assessment of an expanded ROB system developed with guidance from a Technical Expert Panel and NCPTSD, which was pilot tested on a small subset of studies.

Results. We identified 47 new RCTs of interventions for PTSD and 21 RCTs for comorbid PTSD/SUD, resulting in 389 included studies published from 1988 to 2020. Psychotherapy interventions were the most common (63%), followed by pharmacologic interventions (25%). Most studies were conducted in the United States (62%) and had sample sizes ranging from 25 to 99 participants (60%). Approximately half of studies enrolled community participants (55%), and most were conducted in the outpatient setting (72%). Studies typically enrolled participants with a mix of trauma types (53%). Most RCTs (60%) were rated as having a medium ROB, and only 6 percent were rated as having a low ROB. Our pilot testing of an expanded ROB assessment tool emphasized more detailed assessment of elements, including: (1) methods for managing missing data, including both dropout from treatment and missing measurements (i.e., loss to followup); (2) differential assessment of subjective and objective outcomes; and (3) consideration of a five-category overall rating system.

Conclusions. The PTSD-Repository is a comprehensive database of data from PTSD trials. The PTSD-Repository allows clinical, research, education, and policy stakeholders to understand current research on treatment effectiveness and harms, and enable informed decisions about future research, mental health policy, and clinical care priorities. This report updates the studies and variables included in the PTSD-Repository to include recently published trials, interventions targeting comorbid PTSD/SUD, variables related to comorbidities such as suicide and SUDs, and ROB assessment.


O'Neil ME, Cheney TP, Hsu FC, Carlson KF, Hart EL, Holmes RS, Murphy KM, Graham E, Cameron DC, Kahler J, Lewis M, Kaplan J, McDonagh MS. Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: An Update of the PTSD-Repository Evidence Base. Comparative Effectiveness Review No. 235. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 20(21)-EHC029. Rockville, MD: Agency for Healthcare Research and Quality; November 2020. DOI: 10.23970/AHRQEPCCER235. Posted final reports are located on the Effective Health Care Program search page.