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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?
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.
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.
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.
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.
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.
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.
clinicaltrials.gov Identifier: NCT01717963
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Corresponding Author: Lars Tanum, MD, DMSci, The Norwegian Centre for Addiction Research, The University of Oslo, PO Box 1039 Blindern, 0315 Oslo, Norway (firstname.lastname@example.org).
Accepted for Publication: August 25, 2017.
Published Online: October 18, 2017. doi:10.1001/jamapsychiatry.2017.3206
Author Contributions: Dr Kunøe had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Tanum, Kunøe.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Tanum, Solli, Šaltytė Benth, Kunøe.
Critical revision of the manuscript for important intellectual content: Solli, Latif, Šaltytė Benth, Opheim, Sharma-Haase, Krajci, Kunøe.
Statistical analysis: Solli, Šaltytė Benth, Kunøe.
Obtained funding: Tanum, Opheim, Kunøe.
Administrative, technical, or material support: Tanum, Solli, Latif, Opheim, Sharma-Haase, Krajci, Kunøe.
Study supervision: Tanum, Krajci, Kunøe.
Conflict of Interest Disclosures: None reported.
Funding/Support: The study was supported by unrestricted grants from the Research Council of Norway and the Western Norway Regional Health Authority. Financial support was also received from the Norwegian Centre for Addiction Research, University of Oslo, and from Akershus University Hospital.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication; however, Alkermes Inc was allowed to comment on the manuscript before submission for publication.
Additional Contributions: All data analyses were conducted by study-independent statistician Jūratė Šaltytė Benth, PhD (Akershus University Hospital and University of Oslo). Zhanna Gaulen, MSc (Department of Addiction Medicine, Haukeland University Hospital), Anne-Lill Mjoelhus Njaa, MSc (Center for Alcohol and Drug Research, Stavanger University Hospital), and Linn Wergeland Digranes, BSc (Department of Addiction Medicine, Akershus University Hospital), contributed to data collection. There was no financial compensation. Alkermes Inc supplied extended-release naltrexone for the study. We thank all study site personnel for their efforts, as well as all participating patients.
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