Extended-release injectable naltrexone for opioid use disorder: a systematic review

Addiction. 2018 Jul;113(7):1188-1209. doi: 10.1111/add.14180. Epub 2018 Mar 24.


Aims: To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined.

Methods: We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included.

Results: We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification.

Conclusions: Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.

Keywords: Extended-release; heroin; injectable; medication-assisted treatment; naltrexone; opioid use disorder; prescription opioids.

Publication types

  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / poisoning
  • Delayed-Action Preparations
  • Drug Overdose
  • Humans
  • Injections, Intramuscular
  • Medication Adherence
  • Naltrexone / administration & dosage*
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / therapeutic use
  • Opioid-Related Disorders / drug therapy*
  • Treatment Outcome


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Narcotic Antagonists
  • Naltrexone