• This update adds 60 newly published randomized controlled trials (RCTs) on posttraumatic stress disorder (PTSD) and comorbid PTSD/substance use disorder (SUD) to the previous Agency for Healthcare Research and Quality (AHRQ) report on this topic¹ and the National Center for PTSD (NCPTSD) PTSD Trials Standardized Data Repository (PTSD-Repository);² the new total of included RCTs is 496.
• Across all 496 RCTs:
  • The most commonly studied intervention was psychotherapy (44%), followed by pharmacologic interventions (19%), and complementary and integrative health (6%); 7 percent of studies used both pharmacologic and psychotherapeutic interventions.
  • Overall, most studies were conducted in the United States (59%) and had sample sizes in the range of 25 to 99 participants (58%), with a relatively small number of studies enrolling more than 200 participants (8%).
  • Data on race was reported in 57 percent of studies and ethnicity in 31 percent; 42 percent did not provide information on race or ethnicity.
  • Almost a third of studies (32%) targeted specific types of trauma; combat-related trauma was the most commonly targeted (15% of all studies), followed by terrorism/political violence/forced displacement (5%) and accidents (2%); 51 percent allowed a mix of trauma types, and 17 percent did not provide information on participant trauma types.
• Across the 60 newly added RCTs:
  • The most commonly studied intervention was psychotherapy (40%), followed by complementary and integrative health (10%) and nonpharmacologic biologic interventions (8%); 8 percent of studies used both pharmacologic and psychotherapeutic interventions.
  • Just over half of the newly added RCTs were conducted in the United States (53%), enrolled community (not specifically military) participants, and had sample sizes in the range of 25 to 99 participants (53%); a relatively small number of studies enrolled more than 200 participants (7%).
  • 20 percent of studies targeted a specific trauma type, and about half of studies allowed a mix of trauma types (53%); 27 percent did not provide information on participant trauma types.
• This update also includes risk of bias (RoB) using the updated Cochrane RoB 2 tool for randomized trials for all 496 included RCTs.
  • Across all 496 RCTs, RoB was rated as low RoB for 14 percent, some concerns for 27 percent, and high for the remaining studies (60%).
  • Of the 60 newly added RCTs, RoB was rated as low RoB for 17 percent, some concerns for 17 percent, and high for the remaining studies (67%).

Objectives. Identify and abstract data from randomized controlled trials (RCTs) examining treatment for posttraumatic stress disorder (PTSD) and comorbid PTSD/substance use disorder to update the previous Agency for Healthcare Research and Quality (AHRQ) report on this topic and the National Center for PTSD (NCPTSD) PTSD Trials Standardized Data Repository (PTSD-Repository) with newly published trials.

Data sources. We searched PTSDpubs, Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs published from August 1, 2021, to March 3, 2023.

Review methods. In consultation with AHRQ and NCPTSD, we updated the evidence tables for the PTSD-Repository by including evidence published after publication of the last update and expanding abstraction of results to include calculated standardized effect sizes. 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 included studies using the Revised Cochrane Risk of Bias 2 (RoB 2) tool for randomized trials. For studies already in the PTSD-Repository, we will add calculated standardized effect sizes in a future update.

Results. We added 60 new RCTs examining treatments for PTSD, for a total of 496 included studies published from 1988 to March 3, 2023. Among all 496 included RCTs, studies of psychotherapy interventions were the most common (44%), followed by pharmacologic interventions (19%). Most studies were conducted in the United States (59%) and had sample sizes ranging from 25 to 99 participants (58%). Approximately half of the studies enrolled community (i.e., not specifically military) participants (54%), and most were conducted in outpatient settings (78%). Studies typically enrolled participants with a mix of trauma types (51%). Among all 496 included RCTs, RoB was rated as high for 60 percent of studies, 27 percent were rated as having some concerns, and the remaining 14 percent were rated as low RoB.

Among the 60 newly added RCTs, psychotherapy interventions were the most commonly employed (40%), followed by complementary and integrative health (10%). Approximately half of the studies were conducted in the United States (53%), and enrolled community participants (53%) and participants with a mix of trauma types (53%). Studies typically had sample sizes ranging from 25 to 99 participants (53%). Of the newly added RCTs, RoB was rated as high for 67 percent of studies, 17 percent were rated as having some concerns, and the remaining 17 percent were rated as low RoB.

Conclusions. This report updates the previous AHRQ report to include 60 recently published RCTs, for a total of 496 studies. This update adds comprehensive data, standardized effect sizes for PTSD outcomes, and RoB assessment for the newly included RCTs. As with the previous AHRQ update, this report will serve as the updated evidence base for the PTSD-Repository, a comprehensive database of PTSD trials.

1. O’Neil ME, Cheney TP, Yu Y, et al. Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: 2022 Update of the PTSD Repository Evidence Base. Systematic Review. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 75Q80120D00006.) AHRQ Publication No. 22(23)-EHC040. Rockville, MD: Agency for Healthcare Research and Quality; October 2022. doi: 10.23970/AHRQEPCPTSD2022.
2. O’Neil ME, Cheney TP, Hsu FC, et al. 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.
3. O'Neil M, McDonagh M, Hsu F, et al. Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: Groundwork for a Publicly Available Repository of Randomized Controlled Trial Data. Technical Brief No. 32. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 19-EHC018-EF. Rockville, MD: Agency for Healthcare Research and Quality; May 2019. doi: 10.23970/AHRQEPCTB32. PMID: 31145565.
4. O'Neil ME, Harik JM, McDonagh MS, et al. Development of the PTSD-Repository: a publicly available repository of randomized controlled trials for posttraumatic stress disorder. J Trauma Stress. 2020 Aug;33(4):410-9. doi: 10.1002/jts.22520. PMID: 32667076
5. National Center for PTSD. Clinical Trials Database: PTSD-Repository. Washington, DC: U.S. Department of Veterans Affairs. https://www.ptsd.va.gov/ptsdrepository/index.asp. Accessed January 12, 2022.
6. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ Publication No. 10(14)-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality; January 2014. Chapters available at: https://effectivehealthcare.ahrq.gov/topics/cer-methods-guide/overview.
7. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898

Suggested citation: O’Neil ME, Cheney TP, Yu Y, Hart EL, Holmes RS, Blazina I, Clauss K, Veazie SP, Griffin JC, Jungbauer R, Zaccari B, Fu R, Carlson KF, Chou R. Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: 2023 Update of the Evidence Base for the PTSD Trials Standardized Data Repository. Systematic Review. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 75Q80120D00006.) AHRQ Publication No. 23-EHC028. Rockville, MD: Agency for Healthcare Research and Quality; September 2023. DOI: https://doi.org/10.23970/AHRQEPCPTSD2023. Posted final reports are located on the Effective Health Care Program search page.

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