Importance: Buprenorphine-naloxone and extended-release (XR) naltrexone are both efficacious medications for opioid use disorder that reduce unregulated opioid use and improve opioid cravings and treatment retention. While prior comparative effectiveness studies demonstrated superiority of buprenorphine-naloxone over XR naltrexone for relapse and treatment retention, the comparative effectiveness of both treatments for all-cause mortality and nonfatal opioid overdose outcomes has not been rigorously tested.

Question: What is the comparative effectiveness of buprenorphine-naloxone vs extended-release (XR) naltrexone for all-cause mortality and nonfatal opioid overdose among adults after discharge from medically managed opioid withdrawal treatment?

Findings: In this comparative effectiveness study using a target trial emulation framework of 106 052 discharge episodes from opioid withdrawal treatment followed up for 24 weeks, the cumulative incidence of nonfatal overdose was lower for buprenorphine-naloxone than for XR naltrexone, but risk of all-cause mortality was similar between the 2 treatment groups.

Meaning: Findings from this study using observational data provide further evidence of improved outcomes for individuals treated with buprenorphine-naloxone compared with XR naltrexone.