Key messages
– It is unclear whether treating people with opioid use disorder in a primary care setting compared to a specialized clinic makes a difference to retention in the treatment program or to major unwanted effects. Primary care management may result in greater avoidance of non-prescribed opioids.
– Confidence in these findings is low or very low, largely because participating primary care clinics and patients were somewhat atypical — making it difficult to generalize our findings to most primary care practices and most people with opioid use disorder.
What is opioid use disorder?
Some opioid medicines are prescribed to treat pain (for example, morphine, oxycodone, hydromorphone), but others can be illegally manufactured and used (for example, heroin and fentanyl, although fentanyl is also available by prescription). Opioid use disorder is where people repeatedly use opioid medicines in ways that pose a risk of harm to themselves or others, often because they have symptoms like craving for opioids or opioid withdrawal sickness (which can include symptoms like anxiety, sweating, muscle aches, problems sleeping, feeling sick, tummy pain, and depression).
How is opioid use disorder treated?
Opioid use disorder is typically treated in specialized clinics where multiple avenues of treatment are often available. This can potentially include 'detoxification' (assistance going through withdrawal from the medicine), counseling, and support services (for example, support with housing, employment, or legal issues). However, the main treatment involves medication — most often the prescribing of long-lasting opioids that provide either similar effects to other opioids (for example, methadone), or muted (partial) effects (for example, buprenorphine). When long-acting opioids are prescribed for this purpose, it is referred to as opioid agonist therapy.
What did we want to find out?
We wanted to know if providing opioid agonist therapy through a primary care clinic, instead of a specialized clinic, provided similar or better results for people with opioid use disorder. Specifically, we wanted to look for differences in whether they:
– continued in treatment ('treatment retention');
– avoided opioid use ('abstinence from non-prescribed opioids');
– had major unwanted effects (like death or hospitalization);
– left the study due to unwanted effects;
– had improved quality of life;
– had improved patient satisfaction;
– died for any reason;
– died due to opioids (for example, overdose);
– were admitted to a hospital or emergency room for any reason;
– were incarcerated for any reason (that is, going to prison); and
– had minor unwanted effects (for example, withdrawal symptoms).
Why did we think this might be beneficial?
Primary care clinics are widespread, making them potentially more accessible. There could be less of a social stigma when one is seen attending a primary care clinic, and regularly attending a primary care clinic could provide greater opportunity for discussion and treatment of a variety of medical conditions that are unrelated to opioid use disorder.
What did we do?
We looked for studies comparing people with opioid use disorder who received opioid agonist therapy in a primary care setting versus a specialty care setting. We assessed the studies for quality and summarized their results.
What did we find?
We found seven studies with 1952 adults with opioid use disorder whose treatment was managed either in primary or specialty care settings. Five studies took place in the USA, one in France, and one in Ukraine. The average age of participants was 38 years, and three in every four were men. The studies excluded people at 'high risk' such as those who were pregnant, homeless, addicted to alcohol, or diagnosed with other mental health conditions.
It was unclear whether retention in the treatment program was any different between groups (7 studies, 1952 people). People managed in a primary care setting may have had better avoidance of non-prescription opioids (5 studies, 428 people), and it was unclear if there was any difference in major unwanted effects (1 study, 93 people).
People treated in primary care may be more satisfied with their care compared with those treated in specialty care, but there were no clear differences in quality of life, death from any cause, and minor unwanted effects. There was no information about the other measures we were interested in.
What are the limitations of the evidence?
Our certainty in the evidence is low overall, largely because people and primary care clinics varied. People tended to be lower-risk and more stable than general, and primary care clinics often had prior experience with opioid use disorder, or connections with specialty clinics that might not be widely available. It is unclear whether these results can be generalized to most people with opioid use disorder (some of whom may be less stable and higher risk), and most primary care providers (some of whom may have no or little experience with treating opioid use disorder).
How up to date is this evidence?
The evidence is current to 7 March 2025.
Read the full abstract
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 strategy
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 (I2 = 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.
