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Cited by 465Opioid Use Disorder TreatmentSubstance Abuse Treatment and OutcomesPain Management and Opioid Use

The DOI matches its Crossref record; 149 of the 149 references it cites were found in a registry or an index; none of the 77 sources its claims cite is checked for support yet.

Maintenance Medication for Opiate Addiction: The Foundation of Recovery

Open access
Bart, Gavin·2012·Journal of Addictive Diseases
DOI 10.1080/10550887.2012.694598PMC PMC3411273
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Abstract

Illicit use of opiates is the fastest growing substance use problem in the United States, and the main reason for seeking addiction treatment services for illicit drug use throughout the world. It is associated with significant morbidity and mortality related to human immunodeficiency virus, hepatitis C, and overdose. Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication-assisted detoxification. This article provides a topical review of the three medications approved by the Food and Drug Administration for long-term treatment of opiate dependence: the opioid-agonist methadone, the partial opioid-agonist buprenorphine, and the opioid-antagonist naltrexone. Basic mechanisms of action and treatment outcomes are described for each medication. Results indicate that maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function. Oral naltrexone is ineffective in treating opiate addiction, but recent studies using extended-release naltrexone injections have shown promise. Although no direct comparisons between extended-release naltrexone injections and either methadone or buprenorphine exist, indirect comparison of retention shows inferior outcome compared with methadone and buprenorphine. Further work is needed to directly compare each medication and determine individual factors that can assist in medication selection. Until such time, selection of medication should be based on informed choice following a discussion of outcomes, risks, and benefits of each medication.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that long-term maintenance medication is the strongest foundation for recovery from opiate addiction, with methadone and buprenorphine showing better retention and illicit-use outcomes than naltrexone or non-medication approaches. It reviews mechanisms, outcomes, and special populations, and calls for direct comparative studies to guide individualized medication choice.

Key findings

  • Non-medication treatment and detoxification have poor outcomes: more than 80% return to opiate use within two years after intensive residential treatment, and medication-assisted detoxification does not sustain abstinence beyond initial stabilization.
  • Methadone and buprenorphine maintenance reduce illicit opiate use and craving and improve retention and social function. Methadone stabilization is usually 60–120 mg daily, with mean 1-year retention around 60% and roughly 15% of patients showing ongoing illicit opiate use at any time. Buprenorphine stabilization is usually 12–16 mg daily; 12–24 week retention is similar to methadone, and one small placebo-controlled trial reported 1-year retention of 75% versus 0%.
  • Oral naltrexone is ineffective largely because of poor adherence: fewer than 20% remain in treatment at 6 months, and a Cochrane meta-analysis found it no better than placebo. Extended-release naltrexone shows promise: one trial retained 70% at 8 weeks; a larger Russian trial retained 53% versus 38% for placebo at 6 months; implants showed about 60% retention at 6 months, but indirect comparison suggests inferior retention to methadone and buprenorphine.
  • One randomized comparison found 24-week retention of 84% for methadone 50 mg, 59% for buprenorphine 5 mg, and 21% for naltrexone 50 mg, despite suboptimal methadone and buprenorphine doses. No direct comparisons exist between extended-release naltrexone and either methadone or buprenorphine.

Methods

  • Narrative/topical review of the three FDA-approved medications for long-term opiate dependence: methadone, buprenorphine, and naltrexone. It covers neurobiology, psychosocial-only and detoxification approaches, mechanisms of action, treatment outcomes, direct comparisons, and special populations.
  • Evidence is drawn from existing literature, systematic reviews, and clinical trials; no new primary data collection or formal systematic search/meta-analysis is described.
  • Outcomes emphasized include retention in treatment, illicit opiate use, craving, social function, and safety.

Limitations

  • Stated: no randomized double-blind trial compares all three medications; no direct outcome studies compare extended-release naltrexone with methadone or buprenorphine; buprenorphine studies mostly last 12–24 weeks, so whether retention similarity persists at 1 year is uncertain; more work is needed on direct comparisons and predictors of individual response.
  • Stated: oral naltrexone evidence is limited by high dropout, and extended-release naltrexone data remain limited.
  • Evident: as a topical review, it lacks a described systematic search strategy, inclusion criteria, or formal quality assessment; some special-population recommendations rest on limited or no formal studies, such as buprenorphine pharmacokinetics in end-stage liver disease.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1080/10550887.2012.694598

Cites

149 of 149 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 77 cited sources checked · 0 supported · 0 flagged

Show all 44 claims

  • It may state two separate claims as one. 30
  • Probably not a substantial claim. 3
31 of 31

  • The authors state this as an assumption.

    Buprenorphine's therapeutic effect in opiate addiction is mediated through partial agonism at the mu opioid receptor.

    “The neurobiological effect of buprenorphine in the treatment of opiate addiction is presumed to be mediated through partial agonism of the mu opioid receptor.”

  • The paper relies on this without support.

    An indirect comparison of retention between extended-release naltrexone and methadone or buprenorphine can validly indicate their relative outcome.

    “indirect comparison of retention shows inferior outcome compared to methadone and buprenorphine”

  • The paper relies on this without support.

    Findings from alcoholism treatment about naltrexone's reduction of craving can inform its use in opiate addiction.

    “What may be most compelling about naltrexone comes from the literature on its use in the treatment of alcoholism where it reduces craving, a frequent predecessor to relapse.”

  • The paper relies on this without support.

    No randomized double-blind controlled trials have compared all three medications (methadone, buprenorphine, naltrexone) for opiate addiction.

    “There are no randomized double-blind controlled trials comparing all three medications.”

  • The paper relies on this without support.

    No comparative outcome studies exist between methadone or buprenorphine and extended-release naltrexone.

    “There are no comparative outcome studies between either methadone or buprenorphine and extended release naltrexone.”

  • The paper relies on this without support.

    No formal studies of buprenorphine pharmacokinetics in end-stage liver disease exist.

    “There are no formal studies of buprenorphine pharmacokinetics in end stage liver disease.”

  • The paper relies on this without support.

    FDA labels for oral and intramuscular naltrexone recommend against their use in end-stage liver disease.

    “FDA labels for both oral and intramuscular naltrexone recommended against their use in the setting of end stage liver disease.”

  • The paper relies on this without support.

    The placenta is metabolically active and can increase clearance of methadone and buprenorphine.

    “The placenta is metabolically active and can increase clearance of both methadone and buprenorphine.”

  • The paper relies on this without support.

    Both methadone and buprenorphine are associated with improved maternal and fetal outcomes compared to abstinence-based approaches.

    “Both methadone and buprenorphine are associated with improved maternal and fetal outcomes compared to abstinence based approaches.”

  • The paper relies on this without support.

    Opiate addiction is often a disease of pediatric onset.

    “Opiate addiction is often a disease of pediatric onset.”

  • The paper relies on this without support.

    Many maintenance patients with chronic pain may require daily or intermittent opioid analgesics.

    “Many of these patients may require daily or intermittent opioid analgesics.”

  • The paper relies on this without support.

    Methadone and buprenorphine have been used for moderate to severe pain.

    “Both methadone and buprenorphine have been used in the treatment of moderate to severe pain”

  • The paper relies on this without support.

    Chronic use of methadone or buprenorphine for opiate addiction does not preclude regular use of opioid analgesics.

    “their chronic use for opiate addiction does not preclude the regular use of opioid analgesics.”

  • The paper relies on this without support.

    Naltrexone can prevent the effectiveness of opioid analgesics.

    “Naltrexone can prevent the effectiveness of opioid analgesics.”

  • The paper relies on this without support.

    No direct comparisons of these medications have been performed in a criminal justice setting.

    “No direct comparisons of these medications have been performed in a criminal justice setting.”

  • The paper relies on this without support.

    Naloxone and naltrexone are Category C.

    “although each are Category C”
16 of 16

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?

Citations

Cites

1 retracted

Flagged first, then by citations

Show all 147 references

Research works printed but not linked: 14

  1. World Health Organization, 2009, Global health risks: mortality and burden of disease attributable to selected major risks
  2. Salomon N, 2000, Int J Tuberc Lung Dis, 4, 47
  3. Centers for Disease Control and Prevention, 2011, MMRW, 60, 1487
  4. Substance Abuse and Mental Health Services Administration, Results from the 2010 National Survey on Drug Use and Health: summary of national findings
  5. Pescor M J, 1943, Publ Health Rep, 170, 1
  6. Mayet S, 2005, Cochrane Database Syst Rev
  7. Mattick R P, 2003, Cochrane Database Syst Rev
  8. Amato L, 2005, Cochrane Database Syst Rev
  9. Kleiderer E C, 1945, Pharmaceutical activities at the I.G. Farbenindustrie plant, Hochst am Main. 981
  10. Pfohl D N, 1986, NIDA Res Monogr, 67, 66
  11. Volavka J, 1976, Biol Psychiatry, 11, 679
  12. National Institutes of Health, 1976, Narcotic antagonists: naltrexone progress report
  13. Volpicelli J R, 1995, J Clin Psychiatry, 56, 39
  14. Ling W, 1984, J Clin Psychiatry, 45, 46

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Metadata

Authors
Bart, G.
Affiliations
University of Minnesota (US)
Corresponding author
Bart, Gavin
ORCID
Bart, Gavin
Venue
Journal of Addictive Diseases
Publisher
Informa UK Limited
Published
2012-07
Volume
31
Issue
3
Pages
207-225
ISSN
  • 1055-0887 (ISSN-L)
  • 1545-0848
DOI
10.1080/10550887.2012.694598
PMC
PMC3411273
OpenAlex
W2088639396
Semantic Scholar
ff99fbcbbfa09ac397c39aa742621c60880a669f
Cited by
461
References
147
Citations by year
2026: 10 · 2025: 16 · 2024: 23 · 2023: 33 · 2022: 35 · 2021: 47 · 2020: 63 · 2019: 48 · 2018: 46 · 2017: 28 · 2016: 33 · 2015: 36 · 2014: 28 · 2013: 15
FWCI
24.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Addictive Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (K23DA024663)
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
opioid use disorder, maintenance therapy, methadone, buprenorphine, naltrexone, medication-assisted treatment, treatment retention, relapse, craving, drug selection
MeSH terms
Analgesics, Opioid, Buprenorphine, Humans, Long-Term Care, Methadone, Naltrexone, Narcotic Antagonists, Opioid-Related Disorders, Substance Withdrawal Syndrome, Treatment Outcome, Opiate Substitution Treatment

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