Treatment efficacy for co-occurring posttraumatic stress disorder (PTSD) and substance use disorders is well established, yet direct evidence for comparative effectiveness across treatments is lacking. The present study compared the effectiveness of several behavioral and pharmacological therapies for adults with co-occurring PTSD and alcohol or other drug use disorders.

A systematic search of PsycINFO, MEDLINE, and ClinicalTrials.gov was conducted through December 2020 for trials targeting PTSD, alcohol or other drug use disorders, or both disorders (36 studies, N=4,046). Primary outcomes were severity scores for PTSD, alcohol use, and drug use, estimated via moderated nonlinear factor analysis. Propensity score weight–adjusted multilevel models were used. Model-predicted effect sizes were estimated for each treatment, and comparative effect sizes for each active arm against treatment as usual, at end of treatment and at 12-month follow-up.

Compared with treatment as usual, combining trauma-focused therapy and pharmacotherapy for substance use disorders showed the largest comparative effect sizes for PTSD severity (d=−0.92, 95% CI=−1.57, −0.30) and alcohol use severity (d=−1.10, 95% CI=−1.54, −0.68) at end of treatment. Other treatments with large comparative effect sizes included pharmacotherapies for alcohol or other drug use disorders, trauma-focused integrated therapies, and trauma-focused nonintegrated therapies. Reductions in outcomes for PTSD symptoms and alcohol use were observed for nearly all treatments.

The findings provide support for treating comorbid PTSD and substance use disorders using a variety of approaches, with alcohol-targeted pharmacotherapies and trauma-focused behavioral therapies as a combination of treatments that lead to early and sustained improvements in PTSD and alcohol use severity. Further treatment development is indicated for combining behavioral and pharmacological treatments for synergized impact and understanding the mechanisms of action and conditions under which each treatment type is optimized.