BACKGROUND: Opioid use disorder (OUD) is commonly treated in specialized care settings with long-acting opioid agonists, also known as opioid agonist therapy, or OAT. Despite the rise in opioid use globally and evidence for a 50% reduction in mortality when OAT is employed, the proportion of people with OUD receiving OAT remains small. One initiative to improve the access and uptake of OAT could be to offer OAT in a primary care setting; primary care clinics are more numerous, might reduce the visibility and potential stigma of receiving treatment for OUD, and may facilitate the care of other medical conditions that are unrelated to OUD. However, it is unknown how effective treating OUD in primary care would be.

OBJECTIVES: To assess the benefits and harms of using opioid agonist therapy (OAT) to treat people with opioid use disorder (OUD) in a primary care setting, as compared to a traditional specialty care setting.

SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, three other databases, and two trials registers in March 2025. We did not restrict searches by language or publication date.

SELECTION CRITERIA: Eligible studies were parallel randomized controlled trials (RCTs) and cluster-randomized trials comparing OAT for OUD treatment in primary care versus specialty care settings. Participants were community-dwelling adults with OUD, as identified and defined by trial-specific inclusion criteria. We excluded trials if they included only pregnant women, or those who were incarcerated, but accepted all other comorbidity requirements (e.g. being HIV positive).

DATA COLLECTION AND ANALYSIS: Primary outcomes included treatment retention, abstinence from non-prescribed opioids, major adverse events, and withdrawals due to adverse events. Secondary outcomes were other patient-oriented outcomes, including quality of life, patient satisfaction, all-cause mortality, opioid-related mortality, all-cause hospitalization or emergency room visit, all-cause incarceration, and minor adverse events. Two review authors independently extracted data using a predesigned RCT template in Covidence. We assessed risk of bias using the Cochrane RoB 1 tool, and certainty of evidence using GRADE. We analyzed outcomes using Review Manager and a random-effects model to account for variability in care models and populations.

MAIN RESULTS: We included seven RCTs involving 1992 participants. The studies were completed in France (1 study), Ukraine (1 study), and the US (5 studies), and enrolled predominantly males (75%) with a mean age of 38 years. Risk of bias in individual trials was typically low or unclear in all domains except for blinding, where it was high, given participants and providers could not realistically be blinded to setting. One trial was at high risk of bias related to random sequence generation and another for incomplete outcome data. The evidence is very uncertain whether there was a difference in treatment retention in a primary care setting (risk ratio (RR) 1.15, 95% confidence interval (CI) 0.98 to 1.34; 7 studies, 1952 participants; very low-certainty evidence). Abstinence from non-prescribed opioids at the end of follow-up may have been higher in participants managed in primary care (RR 1.59, 95% CI 1.03 to 2.46; 5 studies, 428 participants; low-certainty evidence). Major adverse events were infrequently reported. Only one trial reported all-cause death (one in primary care versus four in specialty care), but these numbers were too small to be meaningful (very low-certainty evidence). Although data from three studies regarding patient satisfaction could not be combined, patients in primary care may have had greater satisfaction. We downgraded certainty in the evidence twice for indirectness for all outcomes given the studies excluded high-risk patients (e.g. those who were pregnant, had co-dependence on alcohol or benzodiazepines, had psychiatric illness, or were homeless) and primary care providers were often atypical of primary care in general (with connections to, or proximity with, OUD-specialized clinics). We downgraded treatment retention an additional level for inconsistency due to high heterogeneity (I = 69%).

AUTHORS' CONCLUSIONS: For lower-risk people with OUD who were stable on OAT, managing their OAT in primary care, as compared to specialty care, the evidence is very uncertain for treatment retention and may have resulted in better abstinence from non-prescribed opioids and better patient satisfaction. Further trials in primary care clinics that have less experience with, or connection to, OUD specialty clinics is warranted.