Risk of Relapse Among Opioid-Dependent Patients Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone: A Randomized Clinical Trial

Am J Addict. 2021 Sep;30(5):453-460. doi: 10.1111/ajad.13151.


Background and objectives: Compare the risk of relapse to heroin and other illicit opioids among opioid-dependent patients receiving treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX).

Methods: Re-analyzed data from a 12-week multicenter, open-label, randomized treatment study with a subsequent 36-week open-label follow-up study. All patients, N = 143, had completed detoxification and received at least one dose of study medication.

Results: Of 143 patients (72% men), mean age 36 years, 71 received XR-NTX and 72 BP-NLX. The risk of first relapse and the risk of any relapse to heroin and other illicit opioids were both significantly lower in the XR-NTX group compared with the BP-NLX group (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28-0.76; P = .002, and HR, 0.11; 95% CI, 0.04-0.29; P < .001, respectively) and (HR, 0.15; 95% CI, 0.09-0.27; P < .001 and HR, 0.05; 95% CI, 0.03-0.09; P < .001, respectively). There was a stable low risk of relapse among participants receiving XR-NTX in the follow-up.

Discussion and conclusions: Compared to BP-NLX, patients on XR-NTX had a substantially reduced risk of relapse to illicit opioids and showed a stable low risk of relapse over time in longer-term treatment.

Scientific significance: Our data support XR-NTX as a first-line treatment option for patients with opioid addiction both in short and longer-term treatment. This is the first European study showing that XR-NTX significantly reduces the risk of first and any relapse to heroin use in opioid-dependent patients compared to BP-NLX. Our data contradict previous data from the X:BOT study, showing no significant difference in relapse risk between the groups in a 6-month randomised controlled trial. (© 2021 Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry). (Am J Addict 2021;30:451-458).

Trial registration: ClinicalTrials.gov NCT01717963.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / therapeutic use
  • Buprenorphine, Naloxone Drug Combination* / therapeutic use
  • Delayed-Action Preparations / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intramuscular
  • Male
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / therapeutic use
  • Opioid-Related Disorders* / drug therapy
  • Recurrence


  • Analgesics, Opioid
  • Buprenorphine, Naloxone Drug Combination
  • Delayed-Action Preparations
  • Narcotic Antagonists
  • Naltrexone

Associated data

  • ClinicalTrials.gov/NCT01717963