Project Harmony: A Systematic Review and Network Meta-Analysis of Psychotherapy and Pharmacologic Trials for Comorbid Posttraumatic Stress, Alcohol, and Other Drug Use Disorders

We conducted a systematic review and network meta-analyses (NMA) of psychotherapy and pharmacologic treatments for individuals with co-occurring posttraumatic stress disorder (PTSD) and alcohol or other drug use disorder (AOD). A comprehensive search spanning 1995-2019 yielded a pool of 39 studies for systematic review, including 24 randomized controlled trials for the NMA. Study interventions were grouped by target of treatment (PTSD + AOD, PTSD-only, and AOD-only) and approach (psychotherapy or medication). Standardized mean differences (SMD) from the NMA yielded evidence that at the end of treatment, integrated, trauma-focused therapy for PTSD + AOD was more effective at reducing PTSD symptoms than integrated, non-trauma-focused therapy (SMD = −0.30), AOD-focused psychotherapy (SMD = −0.29), and other control psychotherapies (SMD = −0.43). End-of-treatment alcohol use severity was less for AOD medication compared to placebo medication (SMD = −0.36) and trauma-focused therapy for PTSD + placebo medication (SMD = −0.67), and less for trauma-focused psychotherapy + AOD medication compared to PTSD medication (SMD = −0.53), placebo medication (SMD = −0.50), and trauma-focused psychotherapy + placebo medication (SMD = −0.81). Key limitations include the small number of studies in the NMA for pharmacologic treatments and the lack of demographic diversity apparent in the existing literature. Findings suggest room for new studies that can address limitations in study sample composition, sample sizes, retention, and apply new techniques for conducting comparative effectiveness in PTSD + AOD treatment. Public Significance Statement Roughly half of individuals with posttraumatic stress disorder (PTSD) also meet the criteria for an alcohol and other drug use disorder (AOD) with numerous and costly public health consequences. A systematic review and network meta-analysis characterized the evidence base of psychotherapy and pharmacological interventions for PTSD and AOD. Integrated, trauma-focused interventions targeting both PTSD and AOD were more effective at reducing PTSD symptoms than integrated non-trauma-focused, AOD-focused psychotherapy, and other control psychotherapies. AOD medications with and without trauma-focused therapies were more effective in reducing alcohol use severity than placebo controls. Few treatment studies reported adverse events for any intervention outcomes.