Comparing Extended-Release Injectable Versus Sublingual Emergency Department-Initiated Buprenorphine on Treatment Engagement

Background and Objectives: Fewer than one in five with opioid use disorder (OUD) receive medication treatment; buprenorphine (BUP) initiation during the ED visit may close that gap. Extended release (XR) formulations may overcome existing barriers. We compared buprenorphine sublingual (SL) versus a 7-day injectable (XR) on treatment engagement.

Methods: From 7/2020 to 8/2024, we conducted a randomized clinical trial in 29 EDs across the U.S. Eligibility included individuals ≥ 18 years of age with untreated OUD, and a Clinical Opiate Withdrawal Scale (COWS) score of ≥ 4. Participants randomized to SL received self-start instructions for COWS 4-7 or 8-12mg SL in the ED for COWS ≥ 8; plus, a 7-day prescription for 16mg/day. XR participants received a single 24mg subcutaneous injection equivalent to 16mg/day for 7 days. Participants received ED referral for treatment within 7 days. Primary outcome was engagement in treatment (Engage-Tx) at 7 days; secondary outcomes included Engage-Tx at 30 days, and precipitated withdrawal (PW). Engage-Tx was self-reported and verified by the facility. PW was suspected when COWS score increased ≥ 5 points with final determination adjudicated by external experts. Engage-Tx proportions were compared using weighted generalized estimating equations. The repeated measures model was weighted by the inverse probability of non-dropout and adjusted for site, age, sex, race/ethnicity, housing status, and insurance. Proportions of Engage-Tx are presented along with odds ratios (OR) (95% CI).

Results: Among 1994 randomized participants, mean age 39 (SD 11.8), 68% male, 55% white, 31% black and 15% Hispanic: 51% identified unstable housing, 75% public insurance, 22% were treatment seeking, and 76% had fentanyl positive urines. Engage-Tx at 7 days in XR group was 40.5%, 95%CI (31, 50.3) vs SL 38.5%, 95%CI (29.5, 48.5); OR 1.08 95%CI (0.89, 1.32). Engage-Tx at 30 days was XR 43.8; 95%CI (34.3,53.7) vs SL 44.9% 95%CI (35.2, 55); OR 0.96 95%CI (0.78, 1.18). PW was very infrequent: (XR 0.6%, 95% CI (0.4, 1.7); SL 0.8%, 95%CI (0.4, 1.7%).

Conclusion: ED-initiated SL and XR buprenorphine had similar engagement in treatment of approximately 40% at 7 and 30 days. Impact of COVID-19 on health settings may have limited 7-day follow-up treatment access. A very low rate of PW occurred despite high prevalence of fentanyl, highlighting the ED as an effective setting for safe XR and SL buprenorphine initiation.

Presenter:

  • Yosef Berlyand, MD
Authors

  • Gail D'Onofrio, MD, MS

    Albert E. Kent Professor of Emergency Medicine

    Yale University

    Gail D’Onofrio, MD, MS is the Albert E. Kent Professor of Emergency Medicine and Professor of Medicine and Public Health at Yale University Schools of Medicine and Public Health. She has extensive experience as a leader, researcher, mentor, and educator, internationally known for her work in substance use disorders. As a physician-scientist she has had continual NIH-funding for over two decades, designing and conducting clinical trials that have changed clinical practice. In addition, she was one of the founding members of the Board of Addiction Medicine, that became recognized as a ABMS approved subspecialty in 2016, sponsored by the American Board of Preventive Medicine. Dr. D’Onofrio is the MPI of the New England Consortium Node for the NIDA Clinical Trials Network and is the MPI of both a NIDA-funded and NINDS funded K12 training program. She is committed to preparing young faculty to become independent investigators advancing the science of Emergency and Addiction Medicine. 

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