CoChat
Sign Up
Cited by 253Opioid Use Disorder TreatmentSubstance Abuse Treatment and OutcomesPain Management and Opioid Use

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

Open access
Tanum, Lars, Solli, Kristin Klemmetsby, Latif, Zill-e-Huma, Benth, Jurate Šaltyte, Opheim, Arild, Sharma-Haase, Kamni, Krajci, Peter, Kunøe, Nikolaj·2017·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2017.3206PMC PMC6583381
Open this paper in CoChat — free accountOpen PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1001/jamapsychiatry.2017.3206

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Inverse agonism at μ and κ receptors might limit (2R,6R)-HNK's abuse liability, as naltrexone prevents relapse in opioid and alcohol use disorders, but this needs more study.

    “It is possible that inverse agonism of μ and κ-opioid receptors may help to restrict the potential for abuse of (2R,6R)-HNK similar to how naltrexone helps prevent relapse in opioid and alcohol use disorders, however this assertion requires further research”

    From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Tanum et al., 2017

    The paper’s introduction says extended-release naltrexone can protect against opioid relapse, and its Discussion reports short-term abstinence in people with opioid dependence. It does not study (2R,6R)-HNK or μ- and κ-receptor inverse agonism, and it does not establish relapse prevention in alcohol use disorder. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 43 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Tanum, L., Solli, K. K., Latif, Z.-E.-H., Benth, J. Š., Opheim, A., Sharma-Haase, K., Krajci, P., & Kunøe, N.
Affiliations
  • University of Oslo (NO)
  • Akershus University Hospital (NO)
  • Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway4Health Services Research Unit, Akershus University Hospital, Lorenskog, Norway
  • Haukeland University Hospital (NO)
  • The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway7Department of Addiction Medicine, Vestfold Hospital Trust, Tonsberg, Norway
  • Department of Addiction Medicine, Oslo University Hospital, Oslo, Norway
Corresponding author
Tanum, Lars
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2017-12-01
Volume
74
Issue
12
Pages
1197
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2017.3206
PMC
PMC6583381
OpenAlex
W2766969415
Cited by
253
References
43
Citations by year
2026: 13 · 2025: 21 · 2024: 20 · 2023: 15 · 2022: 25 · 2021: 34 · 2020: 30 · 2019: 47 · 2018: 44 · 2017: 4
FWCI
32.10
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Norges Forskningsråd
  • Haukeland Universitetssjukehus
  • Akershus Universitetssykehus
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
buprenorphine/naloxone, opioid use disorder, heroin use, opioid substitution therapy, abstinence, treatment retention, detoxification, intramuscular injection, non-inferiority, illicit drug use, treatment safety, addiction treatment centers, Norway
MeSH terms
Buprenorphine, Naloxone Drug Combination, Administration, Oral, Adult, Delayed-Action Preparations, Female, Humans, Injections, Intramuscular, Male, Naloxone, Narcotic Antagonists, Opioid-Related Disorders, Psychiatric Status Rating Scales, Substance Abuse Detection, Treatment Outcome, Drug Monitoring, Diagnostic and Statistical Manual of Mental Disorders, Opiate Substitution Treatment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review