Extended-Release and Sublingual Buprenorphine Are Effective Managing OUD in Emergency Department Settings

In patients with opioid use disorder (OUD) receiving treatment with buprenorphine, there was no difference in treatment engagement between extended-release and sublingual formulations. Additionally, both formulations were well-tolerated and withdrawal was rare, despite a high prevalence of opioid misuse.¹

When is Buprenorphine Used?

Buprenorphine is a synthetic opioid developed and FDA approved to treat both acute and chronic pain as well as opioid dependence. Off-label, it is limited to injection and includes perineural anesthesia as well as withdrawal management in patients hospitalized for heroin dependence. The drug is a synthetic analog of thebaine, an alkaloid compound derived from the poppy flower.

Buprenorphine is categorized as a schedule 3 drug, meaning that it has a moderate to low potential for physical dependence or a high potential for psychological dependence.²

Buprenorphine is used in agonist substitution treatment—a method for addressing addiction by substituting a more potent full agonist opioid, such as heroin, with a less potent opioid, such as buprenorphine or methadone.²

The Study’s Design and What the Findings Uncovered

The investigators wrote that extended-release injectable buprenorphine has the potential to expand the reach of initiating medications for OUD in high-risk and hard-to-reach individuals who visit the ED, and could even be administered in low levels of withdrawal. They compared the effect of ED-initiated 7-day extended-release injectable buprenorphine with sublingual buprenorphine on treatment engagement.

This multicenter, randomized clinical trial (NCT04225598) enrolled adult patients presenting to the ED with untreated OUD and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or higher. Patient data was gathered from 29 US EDs from July 12, 2020, to August 21, 2024, and final follow-up was completed on October 24, 2024.^1,3

Patients were randomly assigned to receive a 24-mg injection of extended-release buprenorphine or sublingual buprenorphine, which included either self-administration instructions if the COWS score was less than 8 or administration of 8 mg of sublingual buprenorphine in the ED if the COWS score was 8 or higher.

All sublingual buprenorphine group patients received a 7-day prescription for 16 mg per day. Regardless of their treatment method, all patients were provided a referral for ongoing medication with a scheduled appointment within 7 days.^1,3

The trial’s primary end point was engagement in OUD on day 7, and secondary end points included engagement at 30 days, precipitated withdrawal and overdose events, craving scores, days of illicit opioid use, and patient satisfaction with treatment.^1,3

A total of 1994 patients (median age: 37 years; IQR, 30–47 years) were enrolled and randomly assigned to either the extended-release group (n = 991) or the sublingual group (n = 1003). Most of the participants were male (68%) and tested positive for fentanyl (76%). Additionally, approximately 31% of patients had an initial COWS score of 4 to 7.¹

The adjusted proportion of engagement in OUD treatment at 7 days was higher in the extended-release group (40.5%) compared with the sublingual group (38.5%; adjusted difference, 1.6% [95% CI, –2.8% to 6.0%]); however, engagement at 30 days was similar, with adjusted proportions of 43.8% with extended-release buprenorphine compared with 44.9% with sublingual buprenorphine (adjusted difference, –1.5% [95% CI, –6.2% to 3.2%]).¹

Further, precipitated withdrawal was rare, with only 6 patients (0.6%) with extended-release buprenorphine and 8 patients (0.8%) with sublingual buprenorphine recorded during this study. Overdose events within 30 days occurred in 18 participants (2.3%) in each group.

Patients who were treated with extended-release buprenorphine reported lower mean craving scores at 7 days compared with those receiving sublingual buprenorphine (scale, 1–100; 26.5 vs 30.2, respectively; 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 better treatment satisfaction scores (scale, 1–5; adjusted mean difference, 0.13 [95% CI, 0.01–0.25]).¹

Overall, these findings suggest that both extended-release injectable and sublingual buprenorphine are safe, effective options for initiating OUD treatment in ED settings, with similar rates of treatment engagement at both 7 and 30 days. Although extended-release buprenorphine did not significantly improve engagement compared with sublingual therapy, it was still associated with modest improvements in craving, illicit opioid use, and patient satisfaction, which may be especially meaningful for individuals who face barriers to daily medication adherence.

Expanding access to multiple buprenorphine formulations may help health care professionals tailor treatment to patient needs and strengthen pathways to ongoing care amid the opioid crisis.

REFERENCES

1. D'Onofrio G, Herring AA, Hawk KF, et al; ED INNOVATION Investigators. Emergency Department-Initiated Buprenorphine for Opioid Use Disorder: A Randomized Clinical Trial. JAMA. 2026 Feb 11. doi:10.1001/jama.2025.27019. Epub ahead of print. PMID: 41670966.

2. Kumar R, Viswanath O, Saadabadi A. Buprenorphine. StatPearls [Internet]. Updated June 8, 2024. Accessed February 11, 2026. https://www.ncbi.nlm.nih.gov/books/NBK459126/

3. Emergency Department-Initiated Buprenorphine Validation Network Trial. ClinicalTrials.gov identifier: NCT04225598. Updated January 10, 2025. Accessed February 11, 2026. https://clinicaltrials.gov/study/NCT04225598