Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine

Am J Psychiatry. 2017 May 1;174(5):459-467. doi: 10.1176/appi.ajp.2016.16050548. Epub 2017 Jan 10.


Objective: At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone.

Method: Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone.

Results: Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline.

Conclusions: These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

Trial registration: ClinicalTrials.gov NCT01377610.

Keywords: Buprenorphine; Detoxification; Injectable Naltrexone; Naltrexone; Opioid Dependence; Outpatient.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Ambulatory Care*
  • Behavior Therapy
  • Buprenorphine / administration & dosage*
  • Clonidine / administration & dosage
  • Combined Modality Therapy
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Naltrexone / administration & dosage*
  • Opioid-Related Disorders / rehabilitation*
  • Remission Induction
  • Secondary Prevention
  • Young Adult


  • Delayed-Action Preparations
  • Buprenorphine
  • Naltrexone
  • Clonidine

Associated data

  • ClinicalTrials.gov/NCT01377610