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Original Investigation
December 2017

Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid DependenceA Randomized Clinical Noninferiority Trial

Author Affiliations
  • 1The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway
  • 2Department.of Research and Development in Mental Health Service, Akershus University Hospital, Lorenskog, Norway
  • 3Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway
  • 4Health Services Research Unit, Akershus University Hospital, Lorenskog, Norway
  • 5Department of Addiction Medicine, Haukeland University Hospital, Haukeland, Norway
  • 6Faculty of Medicine & Odontology, The University of Bergen, Bergen, Norway
  • 7Department of Addiction Medicine, Vestfold Hospital Trust, Tonsberg, Norway
  • 8Department of Addiction Medicine, Oslo University Hospital, Oslo, Norway
JAMA Psychiatry. 2017;74(12):1197-1205. doi:10.1001/jamapsychiatry.2017.3206
Key Points

Question  Are monthly intramuscular injections with extended-release naltrexone hydrochloride as effective as daily oral buprenorphine–naloxone hydrochloride in reducing the use of heroin and other illicit substances in newly detoxified, opioid-dependent individuals?

Findings  In this 12-week, open-label randomized clinical trial including 159 opioid users, treatment with intramuscular extended-release naltrexone was as effective as oral buprenorphine-naloxone in reducing the use of heroin, opioids, and other illicit substances.

Meaning  Maintaining short-term opioid abstinence with extended-release naltrexone should be considered an equal treatment alternative to buprenorphine-naloxone as medication-assisted treatment for opioid-dependent individuals.

Abstract

Importance  To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence.

Objective  To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals.

Design, Setting and Participants  A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants.

Interventions  Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks.

Main Outcomes and Measures  Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting.

Results  Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, −0.1; with 95% CI, −0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, −0.04 to 0.2; P < .001) and use of heroin (mean difference, −3.2 with 95% CI, −4.9 to −1.5; P < .001) and other illicit opioids (mean difference, −2.7 with 95% CI, −4.6 to −0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use.

Conclusions and Relevance  Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals.

Trial Registration  clinicaltrials.gov Identifier: NCT01717963

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