Buprenorphine-Naloxone Cuts Nonfatal Overdose vs XR Naltrexone Post-Withdrawal

For pharmacists managing opioid use disorder transitions, this large target trial emulation quantifies real-world overdose differences between buprenorphine-naloxone and extended-release naltrexone that randomized trials were too small to detect.

buprenorphine-naloxoneextended-release naltrexoneopioid use disorderMOUDopioid overdoseall-cause mortalitytarget trial emulationcomparative effectivenessX:BOTaddiction medicine Pain / Palliative Care

Background Information

Buprenorphine-naloxone reduces overdose risk more effectively than XR naltrexone.

Comparing buprenorphine-naloxone and extended-release naltrexone helps identify safer and more effective treatments for opioid use disorder and reduces risks such as overdose. Buprenorphine-naloxone showed a lower incidence of nonfatal opioid overdose (11.6%) compared to XR naltrexone (13.9%), with similar all-cause mortality rates at 24 weeks. This study provides evidence to prefer buprenorphine-naloxone over XR naltrexone for lowering overdose risk following opioid withdrawal, though both treatments show similar mortality outcomes. Buprenorphine-naloxone reduces the risk of nonfatal opioid overdoses compared to XR naltrexone post-withdrawal.

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Authors: Hsu HE, Lodi S, Yan S, Bovell-Ammon BJ, Christine PJ, Tilhou AS, Bernson D, Novo P, Lee JD, Rotrosen J, Liebschutz JM, Walley AY, Larochelle MR

Citation: Hsu HE, Lodi S, Yan S, et al. Buprenorphine-Naloxone vs Extended-Release Naltrexone Following Opioid Withdrawal Treatment. JAMA network open. 2026;9(7):e2623280. doi:10.1001/jamanetworkopen.2026.23280

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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Executive Summary

Study Design

Patient Population

Primary Outcomes

Secondary Outcomes & Safety Profile

Pharmacist Implications

Clinical Pearls

Limitations

Controversies & Evidence Gaps

Cost & Logistics

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