Highlight
– A hybrid type 2a cluster randomized trial (24 US primary care clinics) compared collaborative care for mental health alone versus collaborative care that also included opioid use disorder (OUD)–specific components.
– Among 254 patients with OUD and co-occurring mental health symptoms, the OUD-enhanced collaborative care intervention produced a clinically meaningful reduction in past-month opioid use compared with active control (adjusted ratio of odds ratio 0.10; 95% CI, 0.03–0.38; Cohen d = -0.44; P < .001).
– Mental health outcomes improved modestly in both arms, with no between-group difference at 6 months.
Background
Medications for opioid use disorder (MOUD) — buprenorphine, methadone, and extended-release naltrexone — are the criterion-standard treatment for opioid use disorder (OUD) and reduce overdose risk and other harms. Despite strong evidence, MOUD remains underused: in many settings fewer than one-quarter of people meeting criteria for OUD receive MOUD. Primary care is a logical venue to expand access because it is widely available, offers longitudinal relationships, and can integrate treatment for co-occurring mental health conditions.
Collaborative care models (CCM) adapt a team-based, measurement-driven approach (primary care clinician, care manager, psychiatric consultant) that has robust evidence for depression and anxiety. Translating CCM to treat OUD — by adding MOUD training, addiction-focused measurement-based care, and brief psychotherapy for OUD — is a promising strategy to increase MOUD uptake and improve outcomes, but randomized effectiveness data have been limited.
Study design
This pragmatic hybrid type 2a cluster randomized clinical trial, reported by Fortney et al., randomized 24 US primary care clinics to either an active control CCM for mental health or an intervention CCM that included OUD-specific components. The trial purposefully evaluated implementation and effectiveness simultaneously (hybrid design).
Key features:
– Clusters: 24 primary care clinics randomized to control or intervention.
– Population: Adults with OUD and co-occurring mental health symptoms who were not receiving specialty mental health or specialty substance use care. Total enrolled = 254 (mean age 40.9 years; 59.9% women).
– Baseline MOUD use: Most participants (172 of 212 with available data; 81.1%) were already taking MOUD at baseline.
– Interventions: Control CCM included primary care clinicians, care managers delivering engagement, self-management, shared decision-making, measurement-based care for mental health, and brief psychotherapy for mental health; psychiatric consultants supported psychotropic prescribing. The intervention arm added MOUD training and psychiatric consultation focused on OUD, measurement-based care for OUD, and brief psychotherapy targeting OUD.
– Outcomes: Co-primary outcomes were past-month number of days of opioid use and the Veterans RAND 12-item Mental Health Component Summary (MCS) score. Research assessments occurred at baseline, 3 months, and 6 months.
– Analysis timeframe: Study data analyzed February 2024 to January 2025. Trial registration: NCT04600414.
Key findings
Primary outcome — opioid use
Both groups reduced days of opioid use over the 6-month follow-up, but the intervention that incorporated OUD-specific collaborative care reduced opioid use significantly more than the mental-health-only CCM. The reported adjusted ratio of odds ratio was 0.10 (95% CI, 0.03–0.38), with a medium effect size (Cohen d = -0.44) and P < .001. This indicates a clinically meaningful additional reduction in opioid use attributable to adding MOUD-focused components to collaborative care in primary care settings.
Primary outcome — mental health
Mental health symptoms (MCS score) improved slightly in both groups over 6 months. The between-group difference in change favored neither arm (adjusted difference in change, -1.20; 95% CI, -4.97 to 2.57; Cohen d = -0.09; P = .53), meaning that augmenting collaborative care with OUD-specific elements did not confer an additional measurable mental health benefit within 6 months compared with collaborative care for mental health alone.
Baseline MOUD use and implications for interpretation
A notable feature of the sample is the high baseline prevalence of MOUD use (≈81% of participants with available data). This limits the extent to which the trial can inform whether the intervention increases MOUD initiation among MOUD-naïve patients. The observed treatment effect therefore likely reflects improved engagement, retention, adherence, or reductions in opioid use intensity among patients already prescribed MOUD, as well as benefits for the subset not yet receiving MOUD.
Other outcomes and safety
The trial report emphasizes effectiveness on opioid use and mental health outcomes. Adverse events or safety endpoints are not described in the summary abstract; readers should consult the full text for detailed safety and retention data. Given the pragmatic primary-care setting and MOUD-prescribing clinicians, safety monitoring and access to specialist consultation were integrated into the intervention.
Effect size and clinical relevance
A medium effect size (Cohen d ≈ -0.44) for reduction in opioid use denotes a meaningful clinical benefit in a population with substantial baseline MOUD exposure. Reductions in days of opioid use are associated with lower overdose risk and better functional outcomes, although the trial’s 6-month horizon limits evaluation of long-term outcomes such as sustained remission, overdose events, or mortality.
Expert commentary and interpretation
Why might CCM for OUD work? Collaborative care operationalizes several evidence-based mechanisms: regular systematic measurement (enabling early detection of deterioration), care management to enhance engagement and adherence, decision support and access to psychiatric/addiction consultation, and brief psychotherapies tailored to patient needs. For OUD, adding clinician training in MOUD, measurement-based OUD monitoring (e.g., craving, use days, urine testing where appropriate), and OUD-focused behavioral interventions likely improves the delivery and optimization of MOUD within primary care workflows.
Strengths of the trial include its pragmatic, cluster-randomized design across multiple clinics, focus on real-world implementation (hybrid design), and measurement-based outcomes. The active control arm (CCM for mental health) is a rigorous comparator that isolates the incremental benefit of OUD-specific components rather than the effect of collaborative care in general.
Limitations to consider: the short follow-up (6 months) restricts insights about durability; the high baseline MOUD prevalence constrains assessment of initiation effects; potential cluster-level heterogeneity (clinic resources, urban vs rural, staffing) may influence generalizability; and the summary does not report detailed safety or adverse-event data. Implementation fidelity, costs, and staffing implications are critical variables for scale-up that require further reporting or study.
Clinical and policy implications
For clinicians and health systems:
– Primary care clinics with MOUD prescribers should consider implementing collaborative care frameworks that explicitly include OUD measurement and treatment components. Doing so may reduce opioid use beyond what mental-health-focused collaborative care alone accomplishes.
– Key operational elements include care managers trained in addiction engagement, routine measurement of opioid use and treatment response, accessible psychiatric/addiction consultation for primary care prescribers, and clinician training to optimize MOUD prescribing and retention.
For payers and policymakers:
– Sustainable payment models, workforce development (training and hiring of care managers), and removal of regulatory barriers to MOUD in primary care are important enablers. Reimbursement for care management and collaborative care activities, plus investments in training and teleconsultation infrastructure, can facilitate broader adoption.
Research gaps and future directions
Important questions remain:
– Does CCM for OUD increase MOUD initiation in patients not already receiving MOUD, especially in settings without existing MOUD prescribers?
– What are the long-term outcomes (12 months and beyond) for opioid use, overdose events, quality of life, and mortality?
– What is the cost-effectiveness of implementing OUD-enhanced collaborative care at scale, and what staffing models are most efficient?
– How does the model perform in diverse settings, including rural clinics, safety-net practices, and populations with different sociodemographic profiles?
– Which specific components (e.g., care manager intensity, frequency of measurement, type of psychotherapy) are essential versus optional for benefit?
Conclusion
Fortney et al.’s cluster randomized trial provides compelling evidence that adding OUD-focused components to an established collaborative care model in primary care reduces days of opioid use more than collaborative care targeting mental health alone. While mental health symptoms improved similarly in both arms, the incremental benefit for opioid outcomes supports broader implementation of CCM that explicitly integrates MOUD training, measurement-based OUD care, and addiction-focused brief psychotherapy into primary care teams. Health systems, clinicians, and policymakers should consider investing in collaborative care infrastructure where MOUD prescribing capacity exists, while further research addresses generalizability, long-term outcomes, and cost-effectiveness.
Funding and clinicaltrials.gov
Trial registration: ClinicalTrials.gov Identifier NCT04600414. Funding details are reported in the original publication (Fortney JC et al., JAMA Psychiatry. 2025); readers should consult the article for specific grant and sponsor information.
References
1. Fortney JC, Ratzliff AD, Blanchard BE, et al. Collaborative Care for Opioid Use Disorder in Primary Care: A Hybrid Type 2 Cluster Randomized Clinical Trial. JAMA Psychiatry. 2025 Oct 1;82(10):956-966. doi: 10.1001/jamapsychiatry.2025.2126. PMID: 40833733; PMCID: PMC12368794.
2. Archer J, Bower P, Gilbody S, et al. Collaborative care for depression and anxiety problems. Cochrane Database Syst Rev. 2012 Oct 17;10:CD006525. doi:10.1002/14651858.CD006525.pub2.
3. Substance Abuse and Mental Health Services Administration. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. 2004. (Available from SAMHSA website.)
Thumbnail image prompt (for article artwork)
A warm-toned clinical scene: a primary care clinician and a care manager reviewing a patient chart on a tablet, with an overlay ghost image of a pill bottle labeled ‘MOUD’ and a mental health checklist; setting is a modern primary care exam room, diverse adults, hopeful atmosphere, high realism, editorial medical illustration.
