Which Medications for Opioid Use Disorder Prevent Overdose?

Opioid overdose is a common and serious complication of opioid use disorder (OUD). One of the benefits of medication for OUD (MOUD) is reduction in overdose; this has been demonstrated in numerous studies of methadone and buprenorphine, but there are less data on the effect of naltrexone. Researchers used a database of commercially insured individuals with a diagnosis of OUD initiating MOUD to evaluate fatal and non-fatal overdose risk while on and off treatment.

  • There were 46,846 individuals who received MOUD; buprenorphine was the most common (86%), followed by oral naltrexone (17%), and extended-release naltrexone (3%).
  • The overdose rate while individuals were not receiving treatment was 5.0 per 100 person-years. Those taking buprenorphine had a rate of 2.1; oral naltrexone 6.2; and extended-release naltrexone 3.9.
  • On multivariable analysis, receiving buprenorphine was associated with a significantly reduced risk of overdose compared with not receiving MOUD, with an adjusted hazard ratio (aHR) of 0.40, while receiving oral naltrexone (aHR, 0.93, CI 0.71–1.22) and extended-release naltrexone (aHR, 0.74, CI 0.42–1.31) were not

Comments: This study supports prior research showing that buprenorphine reduces the risk of opioid overdose. It is possible that extended-release naltrexone also reduces the risk, but the numbers were too small to demonstrate this, or to assess its effect relative to buprenorphine. We can say with more confidence that oral naltrexone does not reduce the risk of overdose; this not surprising given that it is not an effective treatment for most with OUD. It is concerning that is it still being used widely for this purpose.

Darius A. Rastegar, MD

Reference: Morgan JR, Schackman BR, Weinstein ZM, et al. Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort. Drug Alcohol Depend. 2019;200:34–39.

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