Research Summary

ED-Initiated 7-Day Extended-Release Injectable vs Sublingual Buprenorphine for Opioid Use Disorder in US Emergency Departments Shows No Engagement Benefit at 7 Days

Edited by:
Ashton L. Stahl

Key Highlights

  • For adult patients presenting to the emergency department with untreated opioid use disorder, treatment engagement at 7 days was similar with 7-day extended-release injectable buprenorphine vs sublingual buprenorphine.
  • Engagement at 30 days was also similar between groups.
  • Precipitated withdrawal was rare in both groups (<1%), despite high fentanyl positivity (76%).

A 7-day extended-release injectable buprenorphine initiation strategy did not improve short-term engagement in opioid use disorder (OUD) treatment compared with emergency department (ED)-initiated sublingual buprenorphine in a large US multicenter randomized trial published online in JAMA.

Among nearly 2000 adult patients presenting to 29 geographically diverse EDs with untreated OUD and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or higher, adjusted engagement in formal OUD treatment at day 7 differed by 1.6 percentage points (40.5% vs 38.5%), with no significant difference detected, according to the study results.

The ED-Initiated Buprenorphine Validation Network Trial (ED INNOVATION) was a parallel, open-label, individually randomized clinical trial conducted across 29 academic and community EDs in the US from July 12, 2020, to August 21, 2024, with final follow-up completed October 24, 2024. Adults (≥18 years) meeting DSM-5 criteria for moderate to severe OUD with opioid-positive urine toxicology and COWS score ≥4 were randomized 1:1 to receive a 24-mg injection of 7-day extended-release buprenorphine (approximately equivalent to 16 mg/d) or sublingual buprenorphine (with ED administration for higher withdrawal or structured self-initiation instructions for lower withdrawal), plus a 7-day prescription for 16 mg/d in the sublingual group. Both groups received referral with a scheduled follow-up appointment within 7 days and were observed for 2 hours after treatment initiation.

Study Findings

Among 2000 randomized participants, 6 enrolled twice and were excluded, leaving 991 in the extended-release group and 1003 in the sublingual group. Median age was 37 years; 68% were men; 31% had baseline COWS scores 4 to 7; and 76% tested positive for fentanyl. The primary outcome was engagement in formal OUD treatment on day 7, verified by the treatment source when patients reported engagement.

At 7 days, adjusted engagement was 40.5% with extended-release buprenorphine vs 38.5% with sublingual buprenorphine (adjusted difference, 1.6%; 95% CI, −2.8% to 6.0%; P = .44). Engagement at 30 days was also similar (43.8% vs 44.9%; adjusted difference, −1.5%; 95% CI, −6.2% to 3.2%). Precipitated withdrawal was rare: 0.6% with extended-release vs 0.8% with sublingual buprenorphine. Overdose events within 30 days occurred in 2.3% of participants in each group. The authors reported lower craving scores at 7 days with extended-release vs sublingual buprenorphine (mean, 26.5 vs 30.2; adjusted mean difference, −3.85; 95% CI, −7.08 to −0.63), fewer days of illicit opioid use in the past 7 days (adjusted ratio of means, 0.77; 95% CI, 0.68-0.95), and higher satisfaction scores (adjusted mean difference, 0.13; 95% CI, 0.01-0.25); they emphasized these secondary findings as hypothesis-generating given the null primary endpoint.

Clinical Implications

According to the study authors, the findings suggest that initiating a 7-day extended-release injectable buprenorphine preparation in the ED does not increase 7-day OUD treatment engagement compared with ED-initiated sublingual buprenorphine, while both approaches were well tolerated and associated with rare, precipitated withdrawal in a population with high fentanyl prevalence.

Expert Commentary

“No difference was detected in opioid use disorder treatment engagement on day 7 between the 7-day extended-release and sublingual buprenorphine groups,” the researchers concluded. “Both buprenorphine formulations were well tolerated; precipitated withdrawal was rare despite a high prevalence of fentanyl.”

Reference

D’Onofrio G, Herring AA, Hawk KF, et al. Emergency department–initiated buprenorphine for opioid use disorder: a randomized clinical trial. JAMA. Published online February 11, 2026. doi:10.1001/jama.2025.27019