Outpatient initiation of direct-to-inject buprenorphine

Fentanyl-involved overdose deaths have surged, yet buprenorphine remains underutilized for opioid use disorder (OUD) treatment, partly due to the risk of precipitated withdrawal during buprenorphine initiation. Direct-to-inject (DTI) buprenorphine using weekly long-acting injectable formulations may reduce this risk with a gradual and sustained rise in serum buprenorphine levels.

To evaluate 90-day treatment retention, withdrawal tolerability, and associated factors following DTI buprenorphine initiation across multiple outpatient safety-net settings.

We conducted a retrospective cohort study of 131 DTI initiations among 114 patients with OUD across San Francisco and Oakland safety-net clinics from March 2024 to May 2025. Patients were initiated on weekly long-acting buprenorphine. We assessed withdrawal severity in the first 24h and calculated continuous treatment retention at 7, 30, and 90 days using pharmacy and chart data.

Mean age was 42 years; 79 % reported fentanyl use, and 67 % were unstably housed or unhoused. In the 24h after injection, 37 % experienced no withdrawal, 31 % experienced mild-moderate withdrawal, and 11 % experienced severe withdrawal, with 21 % missing data. Overall, 72 % continued buprenorphine beyond initial injection, with most transitioning to monthly formulations. Retention rates were 69 % at 7 days, 68 % at 30 days, and 43 % at 90 days. No demographic or clinical factors predicted 90-day retention.

In this retrospective study, DTI buprenorphine initiation demonstrated favorable tolerability and retention in a high-risk population across diverse outpatient settings. This approach may offer a viable pathway to long-acting buprenorphine treatment for individuals using fentanyl who may not tolerate traditional initiation methods.