Rapid Initiation of Extended-release Buprenorphine for Opioid Use Disorder is Feasible

Extended-release (XR) injectable formulations of buprenorphine are a relatively new treatment option for patients with opioid use disorder (OUD). Initiation strategies for both sublingual (SL) and XR buprenorphine are rapidly evolving now that high-potency synthetic opioids such as fentanyl, are ubiquitous in the North American illicit opioid supply. However, the evidence base to guide clinical practice is limited. This industry-funded, multicenter, open-label, randomized controlled trial sought to compare safety and treatment retention among 729 patients receiving: (1) a rapid initiation (RI) strategy (n=474; one dose of 4mg SL buprenorphine followed by XR buprenorphine 300mg one hour later on day one of initiation); or (2) a standard initiation (SI) strategy (n=255; 7–14 days of SL buprenorphine followed by XR buprenorphine 300mg on day 7–14 of initiation). Both groups had the opportunity for a second XR buprenorphine injection seven days after the initial XR buprenorphine injection.

• Overall, 90 percent of all participants received ≤12mg buprenorphine on the first day of initiation, and 11% of all participants experienced precipitated withdrawal after the first dose of SL buprenorphine.
• Of participants in the SI group, 41 percent dropped out before receiving their first XR buprenorphine injection.
• Of participants in the RI group, 14 percent dropped out before receiving the first XR buprenorphine injection.
• Compared with the SI group, 12 percent more participants received the second XR buprenorphine injection in the RI group.
• Among participants exposed to fentanyl (77 percent), retention was 15 percent higher in the RI group.

Comments: This study shows that rapid initiation of XR buprenorphine after one low dose of SL buprenorphine leads to greater retention when compared with receipt of 7–14 days of SL buprenorphine prior to XR buprenorphine initiation, including in individuals exposed to high-potency synthetic opioids. The study’s design may have introduced performance bias because the 7–14-day SL buprenorphine lead-in provided relatively low doses of buprenorphine. Future studies should compare initiation of therapeutic doses of SL buprenorphine with rapid initiation of XR buprenorphine.

Melissa B. Weimer, DO, MCR

Reference: Shiwach R, Le Foll B, Alho H, et al. Rapid vs standard induction to injectable extended-release buprenorphine: a randomized clinical trial. JAMA Netw Open. 2025;8(10):e2537319.