{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:08:59Z","timestamp":1792454939818,"version":"4.5.0"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Standard induction (SI) using transmucosal buprenorphine-naloxone is challenging in individuals who inject opioids, use high doses of opioids, or use synthetic opioids (eg, fentanyl).<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare the effectiveness and safety of rapid induction (RI; single 4-mg dose of buprenorphine-naloxone) vs SI (\u22657 days of buprenorphine-naloxone) followed by extended-release buprenorphine injection.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This multicenter, open-label randomized clinical trial was conducted from October 26, 2021, to January 19, 2024, at 28 outpatient treatment centers in the US and Canada. Treatment-seeking participants with moderate or severe opioid use disorder who inject opioids, use high doses of opioids, or use fentanyl were studied.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were randomized 2:1 to RI or SI before 300-mg injection of extended-release buprenorphine.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end point, retention rate difference at injection 2 (1 week after injection 1), was estimated by a bayesian approach. Posterior probability was estimated for noninferiority of RI to SI (RI\u2009\u2013\u2009SI &amp;gt;\u221210%) and superiority (RI\u2009\u2013\u2009SI &amp;gt;0%). Adverse events (AEs), including investigator-assessed opioid withdrawal symptoms, were reported. Subgroup analyses compared participants with positive or negative fentanyl urine drug screen results.<\/jats:p><\/jats:sec>Results<\/jats:title>Analyses included 729 randomized participants (mean [SD] age, 40.7 [10.4] years; 406 [55.7%] male) who initiated transmucosal buprenorphine per protocol, including 474 in the RI arm and 255 in the SI arm. A total of 560 participants received extended-release buprenorphine injection 1 (409 [86.3%] in the RI arm and 151 [59.2%] in the SI arm), and 452 received injection 2 (314 [66.2%] in the RI arm and 138 [54.1%] in the SI arm). At injection 2, RI was noninferior with higher retention than SI (difference, 11.8%; 95% credible interval [CrI], 4.3%-19.0%; posterior probability greater than 0 was 99.9%). Similarly, among participants with a positive test result for fentanyl, the retention rate differential in favor of RI was 14.8% (95% CrI, 6.5%-23.7%; posterior probability greater than 0 was greater than 99.9%). AE incidence was not statistically different between RI and SI participants (202 [42.6%] vs 93 [35.5%]; difference, 6.1%; 95% CrI, \u22121.3% to 13.4%). Up to injection 2, most AEs were associated with opioid withdrawal.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this multicenter randomized clinical trial, RI had higher retention than SI overall and in patients who tested positive for fentanyl through extended-release buprenorphine injection 2. Administration of injection 2 after 1 week was well tolerated and minimized time below target therapeutic levels of 2 ng\/mL or greater compared with injection after 1 month.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04995029<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.37319","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T15:02:54Z","timestamp":1760454174000},"page":"e2537319","source":"Crossref","is-referenced-by-count":9,"title":["Rapid vs Standard Induction to Injectable Extended-Release Buprenorphine"],"prefix":"10.1001","volume":"8","author":[{"given":"Rajinder","family":"Shiwach","sequence":"first","affiliation":[{"name":"InSite Clinical Research, Desoto, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Le Foll","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, University of Toronto, 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