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Comorbid PTSD and SUD (PTSD+SUD) is associated with greater severity and impairment and poorer treatment outcomes. Several interventions exist to treat PTSD, SUD and PTSD+SUD; however, research has yet to elucidate the indirect pathways underlying treatment for PTSD+SUD. The present study examined how changes in PTSD severity relate to changes in SUD severity across treatment types during and post\u2010treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Observational study using data collected as part of Project Harmony, a virtual clinical trial employing integrative data analysis to compare treatment effectiveness of PTSD+SUD interventions from 36 randomized controlled trials for PTSD+SUD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094046). Multilevel mediated linear growth modeling was used to examine potential outcomes mediation. Each of the eight active treatments was compared to treatment as usual (TAU) for both alcohol and drug use outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Alcohol use severity outcomes were fully or partially mediated by changes in PTSD severity for trauma\u2010focused psychotherapy + AUD medication [\n                      <jats:italic>ab<\/jats:italic>\n                      \u2009=\u2009\u22120.16 (95% confidence interval\u2009=\u2009\u22120.30 to \u22120.04)]; other treatments with mediation effects included trauma\u2010focused integrated psychotherapy, AUD medications and PTSD medications. Drug use severity outcomes were fully or partially mediated by changes in PTSD severity for trauma\u2010focused psychotherapy + AUD medication [\n                      <jats:italic>ab<\/jats:italic>\n                      \u2009=\u2009\u22120.08 (\u22120.18 to \u22120.001)]; other treatments with mediation effects on drug use severity included trauma\u2010focused integrated psychotherapy, AUD medications, PTSD medications and placebo medications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among people with co\u2010occurring post\u2010traumatic stress disorder (PTSD) and substance use disorders (SUD), reductions in alcohol and drug use severity appear to be mediated by reductions in PTSD during treatment. For those with drug use disorders, PTSD reductions appear to mediate further SUD reductions after treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70126","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T08:54:42Z","timestamp":1752137682000},"page":"2245-2257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["How changes in post\u2010traumatic stress disorder (PTSD) severity mediate substance use disorder (SUD) severity during and after treatment for co\u2010occurring PTSD and SUD: Results from Project Harmony"],"prefix":"10.1111","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6954-2882","authenticated-orcid":false,"given":"Denise A.","family":"Hien","sequence":"first","affiliation":[{"name":"Center of Alcohol and Substance Use Studies Rutgers University\u2013New Brunswick  Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-2313","authenticated-orcid":false,"given":"Jordan A.","family":"Gette","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-3688","authenticated-orcid":false,"given":"Shannon M.","family":"Blakey","sequence":"additional","affiliation":[{"name":"RTI International  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-5180","authenticated-orcid":false,"given":"Marilyn L.","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Rutgers Robert Wood Johnson Medical School  Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7683-8737","authenticated-orcid":false,"given":"Sudie E.","family":"Back","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Medical University of South Carolina  Charleston SC USA"},{"name":"Ralph H. 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