Collaborative Care for Opioid Use Disorder and Mental Illness: The CLARO Randomized Clinical Trial.

Importance: Adults with opioid use disorder (OUD), co-occurring with depression and/or posttraumatic stress disorder (PTSD), may benefit from collaborative care. Although collaborative care is an evidence-based model to treat behavioral health conditions in primary care, it has not been widely tested for OUD with co-occurring mental illness. Objective: To determine whether collaborative care, tailored for low-resource settings, improves outcomes for patients with OUD and co-occurring depression and/or PTSD more so than enhanced usual care (EUC). Design, Setting, and Participants: This 2-group single-masked pragmatic randomized clinical trial was conducted in 18 primary care clinics in California and New Mexico from January 8, 2021, to December 5, 2023, and included adult participants with probable OUD as well as major depression and/or PTSD. Data analysis was performed August 2024 to May 2025. Interventions: Six months of a care manager and addiction psychiatrist working with a primary care practitioner to deliver evidence-based treatments for OUD, major depression, and PTSD; care managers were community health workers who monitored and addressed biopsychosocial symptoms and referred patients for psychotherapy. Main Outcomes and Measures: Primary outcomes at 6 months were time to first filled buprenorphine prescription for participants entering the study not taking medication for OUD; cumulative days of prescribed buprenorphine for participants entering the study while not taking methadone, obtained from the state Prescription Drug Program; and Patient Health Questionnaire-9 and PTSD Checklist for DSM-5 scores from participant surveys. Secondary outcomes included days of opioid and other drug use, the Patient-Reported Outcomes Measurement Information System's substance use short form, and the Veterans RAND 12-item health survey. Results: Of 2396 participants assessed for eligibility, 797 were randomized (397 to EUC; 400 to intervention); 433 (54.3%) were female and 364 (45.7%) male, with a mean (SD) age of 40.2 (11.9) years. Six-month survey retention was 68% for EUC and 64% for collaborative care. Adjusted mean (SD) differences on primary outcomes for collaborative care vs EUC were: 7.0 (95% CI, -3.4 to 17.4; P = .19) for days until first buprenorphine prescription; 4.3 (95% CI, -7.4 to 16.0; P = .47) for cumulative days of prescribed buprenorphine; -1.0 (95% CI, -2.3 to 0.3; P = .13) for Patient Health Questionnaire-9 score; and -0.9 (95% CI, -4.6 to 2.8; P = .63) for PTSD Checklist for the DSM-5 score; none were statistically significant. There were also no observed differences between groups for any secondary or exploratory outcomes; both groups improved over baseline. As-treated exploratory analyses showed evidence for improvements in OUD outcomes in the as-treated population. Conclusions and Relevance: This randomized clinical trial found that among participants with OUD co-occurring with depression and/or PTSD, collaborative care did not demonstrate evidence of greater improvements in outcomes compared with EUC. Explanations include a possible spillover effect, spontaneous improvement, or the fit of collaborative care for clinically complex patients and settings with few behavioral health practitioners. Trial Registration: ClinicalTrials.gov Identifier: NCT04559893 and NCT04634279.