Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 5;9(9):CD011117.
doi: 10.1002/14651858.CD011117.pub3.

Opioid agonist treatment for people who are dependent on pharmaceutical opioids

Suzanne Nielsen  1 , Wai Chung Tse  1   2 , Briony Larance  3
Affiliations

Opioid agonist treatment for people who are dependent on pharmaceutical opioids

Suzanne Nielsen et al. Cochrane Database Syst Rev. .

Abstract

Background: There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.

Search methods: We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).

Selection criteria: We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).

Data collection and analysis: We used standard Cochrane methods.

Main results: We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms.

Authors' conclusions: There is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.

Trial registration: ClinicalTrials.gov NCT00913770 NCT02032433 NCT00879996 NCT01559454 NCT00315341 NCT00078130.

PubMed Disclaimer

Conflict of interest statement

SN and BL are named investigators on an implementation trial of buprenorphine depot funded by Indivior, which was not eligible for inclusion in this review. SN and BL did not receive funding for their work on the study neither did they have control over the funds that were received by another institution. That company has no role in the conception of, or decision to submit, this review. SN and BL have received untied educational grants for unrelated work from Seqirus. SN is funded by a National Health and Medical Research Council (NHMRC) fellowship. The NHMRC has no interest in the outcome of the review that could lead to a real or perceived conflict of interest.

WCT: none.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 1: Days of illicit opioid use
1.2
1.2. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 2: Opioid‐positive urine drug screen at treatment completion
1.3
1.3. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 3: Self‐reported substance use (end of treatment)
1.4
1.4. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 4: Retention
1.5
1.5. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 5: Adverse effects
1.6
1.6. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 6: Pain
1.7
1.7. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 7: Risk behaviours
1.8
1.8. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 8: Physical health
1.9
1.9. Analysis
Comparison 1: Full opioid agonists versus different full opioid agonists or partial opioid agonists, Outcome 9: Psychological health
2.1
2.1. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 1: Days of illicit opioid use (7 or 30 days)
2.2
2.2. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 2: Opioid positive (per urine drug screen, last week of treatment maintenance)
2.3
2.3. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 3: Self‐reported opioid use at treatment completion (past 30 days)
2.4
2.4. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 4: Retention
2.5
2.5. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 5: Adverse events
2.6
2.6. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 6: Pain (moderate to extreme pain)
2.7
2.7. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 7: Risk behaviours
2.8
2.8. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 8: Physical health
2.9
2.9. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 9: Psychological health (moderate to extremely anxious or depressed)
2.10
2.10. Analysis
Comparison 2: Full or partial opioid agonist maintenance versus placebo, antagonist, detoxification or psychological treatment only, Outcome 10: Psychological health (continuous)
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Ahmadi 2003 {published data only}
    1. Ahmadi J, Ahmadi K, Ohaeri J. Controlled, randomized trial in maintenance treatment of intravenous buprenorphine dependence with naltrexone, methadone or buprenorphine: a novel study. English Journal of Clinical Investigation 2003;33(9):824-9. - PubMed
    1. Ahmadi J, Ahmadi K. Controlled trial of maintenance treatment of intravenous buprenorphine dependence. Irish Journal of Medical Science 2005;172(4):171-3. - PubMed
D'Onofrio 2015 {unpublished data only}
    1. Busch S, Hawk K, Fiellin D, O'Connor P, Chawarski M, Owens P, et al. Health service use in a randomized clinical trial comparing three methods of emergency department interventions for opioid dependence. Drug and Alcohol Dependence 2015;156:e32. [DOI: 10.1016/j.drugalcdep.2015.07.1005] - DOI
    1. D'Onofrio G, Chawarski M, O'Connor PG, Pantalon MV, Busch SH, Owens PH, et al. Emergency department-initiated buprenorphine for opioid dependence with continuation in primary care: outcomes during and after intervention. Journal of General Internal Medicine 2017;32(6):660-6. - PMC - PubMed
    1. D'Onofrio G, Chawarski MC, O'Connor PG, Pantalon M, Busch S, Owens P, et al. Emergency department-initiated buprenorphine for opioid dependence with continuation in primary care: outcomes during and after treatment. Academic Emergency Medicine 2017;24(Suppl 1):S49. [DOI: 10.1111/acem.13203] - DOI - PMC - PubMed
    1. D'Onofrio G, O'Connor P, Pantalon M, Chawarski M, Busch S, Owens P, et al. A randomized clinical trial of emergency department initiated treatment for opioid dependence: two and six month outcomes. Drug and Alcohol Dependence 2015;156:e53. [DOI: 10.1016/j.drugalcdep.2015.07.1062] - DOI
    1. D'Onofrio G, O'Connor PG, Pantalon MV, Chawarski MC, Busch SH, Owens PH, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA 2015;313(16):1636-44. - PMC - PubMed
Fiellin 2014 {published and unpublished data}
    1. Fiellin D, Schottenfeld R, Cutter C, Moore B, Barry D, O'Conner P. Primary care-based buprenorphine taper v maintenance therapy for prescription opioid dependence. JAMA Internal Medicine 2014;174(12):1947-54. - PMC - PubMed
Lee 2018 {unpublished data only}
    1. Campbell AN, Barbosa-Leiker C, Hatch-Maillette M, Mennenga SE, Pavlicova M, Scodes J, et al. Gender differences in demographic and clinical characteristics of patients with opioid use disorder entering a comparative effectiveness medication trial. American Journal on Addictions 2018;27(6):465-70. [DOI: 10.1111/ajad.12784] - DOI - PMC - PubMed
    1. Fishman M, Wenzel K, Scodes J, Pavlicova M, Campbell AN, Rotrosen J, et al. Examination of correlates of OUD outcomes in young adults: secondary analysis from the XBOT trial. American Journal on Addictions 2021;30(5):433-44. [DOI: ] - PMC - PubMed
    1. Haeny AM, Montgomery L, Burlew AK, Campbell AN, Scodes J, Pavlicova M, et al. Extended-release naltrexone versus buprenorphine-naloxone to treat opioid use disorder among Black adults. Addictive Behaviors 2020;110:106514. [DOI: 10.1016/j.addbeh.2020.106514] - DOI - PMC - PubMed
    1. Harvey LM, Fan W, Cano MA, Vaughan EL, Arbona C, Essa S, et al. Psychosocial intervention utilization and substance abuse treatment outcomes in a multisite sample of individuals who use opioids. Journal of Substance Abuse Treatment 2020;112:58-75. [DOI: 10.1016/j.jsat.2020.01.016] - DOI - PubMed
    1. Jalali A, Ryan DA, Jeng PJ, McCollister KE, Leff JA, Lee JD, et al. Health-related quality of life and opioid use disorder pharmacotherapy: a secondary analysis of a clinical trial. Drug and Alcohol Dependence 2020;215:108221. [DOI: ] - PMC - PubMed
Neumann 2013 {published data only}
    1. Neumann AM, Blondell RD, Jaanimägi U, Giambrone AK, Homish GG, Lozano JR, et al. A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction. Journal of Addictive Diseases 2013;32(1):68-78. - PMC - PubMed
Neumann 2020 {published and unpublished data}
    1. Neumann AM, Blondell RD, Hoopsick RA, Homish GG. Randomized clinical trial comparing buprenorphine/naloxone and methadone for the treatment of patients with failed back surgery syndrome and opioid addiction. Journal of Addictive Diseases 2019;38:33-41. - PMC - PubMed
Saxon 2013 {published and unpublished data}
    1. Crist RC, Li J, Doyle GA, Gilbert A, Dechairo BM, Berrettini WH. Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate. American Journal of Drug and Alcohol 2018;44(4):431-40. [DOI: 10.1080/00952990.2017.1420795] - DOI - PMC - PubMed
    1. Evans EA, Yoo C, Huang D, Saxon AJ, Hser YI. Effects of access barriers and medication acceptability on buprenorphine-naloxone treatment utilization over 2 years: results from a multisite randomized trial of adults with opioid use disorder. Journal of Substance Abuse Treatment 2019;106:19-28. [DOI: 10.1016/j.jsat.2019.08.002] - DOI - PMC - PubMed
    1. Evans EA, Zhu Y, Yoo C, Huang D, Hser YI. Criminal justice outcomes over 5 years after randomization to buprenorphine-naloxone or methadone treatment for opioid use disorder. Addiction 2019;114(8):1396-404. [DOI: 10.1111/add.14620] - DOI - PMC - PubMed
    1. Hser YI, Evans E, Huang D, Weiss R, Saxon A, Carroll KM, et al. Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial. Addiction 2016;111(4):695-705. [DOI: 10.1111/add.13238] - DOI - PMC - PubMed
    1. Hser YI, Zhu Y, Fei Z, Mooney LJ, Evans EA, Kelleghan A, et al. Long-term follow-up assessment of opioid use outcomes among individuals with comorbid mental disorders and opioid use disorder treated with buprenorphine or methadone in a randomized clinical trial. Addiction 2022;117(1):151-61. [DOI: 10.1111/add.15594] - DOI - PMC - PubMed
Woody 2008 {published and unpublished data}
    1. Hammond C, Horner M, Rahman N, Allick A, Pribble C, Matson P. Changes in psychiatric symptoms and opioid use during buprenorphine/naloxone treatment in opioid-dependent youth. American Journal on Addictions 2019;28(3):205-6. [DOI: 10.1002/ajad.12887] - DOI
    1. Hammond CJ, Kady A, Park G, Vidal C, Wenzel K, Fishman M. Therapy dose mediates the relationship between buprenorphine/naloxone and opioid treatment outcomes in youth receiving medication for opioid use disorder treatment. Journal of Addiction Medicine 2021;16(2):e97-e104. [DOI: ] - PubMed
    1. Pecoraro A, Subramaniam G, Woody G, Poole S, Vetter V. Presence/absence of QTc prolongation in buprenorphine-naloxone among youth with opioid dependence. Journal of Addiction Medicine 2016;10(3):E15. [DOI: 10.1097/ADM.0000000000000224] - DOI - PMC - PubMed
    1. Poole SA, Pecoraro A, Subramaniam G, Woody G, Vetter VL. Presence or absence of QTc prolongation in buprenorphine-naloxone among youth with opioid dependence. Journal of Addiction Medicine 2016;10(1):26-33. [DOI: 10.1097/ADM.0000000000000176] - DOI - PMC - PubMed
    1. Woody GE, Poole SA, Subramaniam G, Dugosh K, Bogenschutz M, Abbott P, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA 2008;300(17):2003-11. - PMC - PubMed

References to studies excluded from this review

Amass 1994 {published data only}
    1. Amass L, Bickel, Higgins ST, Hughes JR. A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification. Journal of Addictive Diseases 1994;13(3):33-45. - PubMed
Anglin 2007 {published and unpublished data}
    1. Anglin MD, Conner BT, Annon J, Longshore D. Levo-alpha-acetylmethadol (LAAM) versus methadone maintenance: 1-year treatment retention, outcomes and status. Addiction 2007;102(9):1432-42. - PubMed
Anon 2015 {published data only}
    1. Anon. Patients more likely to engage in treatment at 30 days when given buprenorphine in the ED, referred for follow-up. ED Management 2015;27(8):92-5. - PubMed
Bahji 2018 {published data only}
    1. Bahji A, Bajaj N. Opioids on trial: a systematic review of interventions for the treatment and prevention of opioid overdose. Canadian Journal of Addiction 2018;9(1):26-33. [DOI: ]
Batki 1998 {published data only}
    1. Batki SL, Bradley M, Jones T, Moon J, Schissel M, Masson C. A controlled trial of methadone treatment: preliminary analysis of effects on medical care utilization. Journal of Addictive Diseases 1998;17(2):138.
Bazazi 2017 {published data only}
    1. Bazazi AR, Wickersham JA, Wegman MP, Culbert GJ, Pillai V, Shrestha R, et al. Design and implementation of a factorial randomized controlled trial of methadone maintenance therapy and an evidence-based behavioral intervention for incarcerated people living with HIV and opioid dependence in Malaysia. Contemporary Clinical Trials 2017;59:1-12. [DOI: ] - PMC - PubMed
Brinkley‐Rubinstein 2018 {published data only}
    1. Brinkley-Rubinstein L, McKenzie M, Macmadu A, Larney S, Zaller N, Dauria E, et al. A randomized, open label trial of methadone continuation versus forced withdrawal in a combined US prison and jail: findings at 12 months post-release. Drug and Alcohol Dependence 2018;184:57-63. [DOI: 10.1016/j.drugalcdep.2017.11.023] - DOI - PMC - PubMed
Cameron 2006 {published and unpublished data}
    1. Cameron IM, Matheson CI, Bond CM, McNamee P, Lawrie T, Robinson A, et al. Pilot randomised controlled trial of community pharmacy administration of buprenorphine versus methadone. International Journal of Pharmacy Practice 2006;14(4):243-8.
Chandra 2019 {published data only}
    1. Chandra DK, Bazazi AR, Nahaboo Solim MA, Kamarulzaman A, Altice FL, Culbert GJ. Retention in clinical trials after prison release: results from a clinical trial with incarcerated men with HIV and opioid dependence in Malaysia. HIV Research & Clinical Practice 2019;20(1):12-23. [DOI: 10.1080/15284336.2019.1603433] - DOI - PMC - PubMed
Chopra 2009 {published data only}
    1. Chopra MP, Landes RD, Gatchalian KM, Jackson LC, Buchhalter AR, Stitzer ML, et al. Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine. Experimental and Clinical Psychopharmacology 2009;17(4):226-36. - PMC - PubMed
Cook 2021 {published data only}
    1. Cook RR, Torralva R, King C, Lum PJ, Tookes H, Foot C, et al. Associations between fentanyl use and initiation, persistence, and retention on medications for opioid use disorder among people living with uncontrolled HIV disease. Drug and Alcohol Dependence 2021;228:109077. [DOI: 10.1016/j.drugalcdep.2021.109077] - DOI - PMC - PubMed
Cushman 2015 {published data only}
    1. Cushman PA, Anderson BJ, Moreau M, Stein MD, Liebschutz JM. Buprenorphine initiation and linkage to outpatient buprenorphine treatment does not reduce frequency of injection drug use for inpatient opioid-dependent injection drug users: results of a randomized clinical trial. Journal of General Internal Medicine 2015;30:S114-15.
Cushman 2016 {published data only}
    1. Cushman PA, Liebschutz JM, Anderson BJ, Moreau MR, Stein MD. Buprenorphine initiation and linkage to outpatient buprenorphine do not reduce frequency of injection opiate use following hospitalization. Journal of Substance Abuse Treatment 2016;68:68-73. [DOI: ] - PMC - PubMed
Eder 1998 {published data only}
    1. Eder H, Fischer G, Gombas W, Jagsch R, Stühlinger G, Kasper S. Comparison of buprenorphine and methadone maintenance in opiate addicts. European Addiction Research 1998;4(Suppl 1):3-7. - PubMed
Fiellin 2006 {published data only}
    1. Fiellin DA, Pantalon MV, Chawarski MC, Moore BA, Sullivan LE, O'Connor PG, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. New England Journal of Medicine 2006;355(4):365-74. - PubMed
Fischer 1999 {published and unpublished data}
    1. Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stühlinger G, et al. Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Addiction 1999;94(9):1337-47. - PubMed
    1. Fischer G, Gombas W, Eder H, Jagsch R, Stuhlinger G, Aschauer HN, et al. Buprenorphine vs methadone maintenance treatment for opioid dependence. Nervenarzt 1999;70(9):795-802. - PubMed
Fudala 2003 {published data only}
    1. Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. New England Journal of Medicine 2003;349(10):949-58. - PubMed
Ghalehney 2018 {published data only}
    1. Ghalehney ZS, Ilbeigi S, Arshadi HR, Afshari R. Superiority of buprenorphine over suboxone in preventing addiction relapse in opioid addicts under maintenance therapy: a double-blind clinical trial. Asia Pacific Journal of Medical Toxicology 2018;7(1):1-6.
Gordon 2017 {published data only}
    1. Gordon MS, Kinlock TW, Schwartz RP, O'Grady KE, Fitzgerald TT, Vocci FJ. A randomized clinical trial of buprenorphine for prisoners: findings at 12-months post-release. Drug and Alcohol Dependence 2017;172:34-42. [DOI: ] - PMC - PubMed
Gordon 2018 {published data only}
    1. Gordon MS, Blue TR, Couvillion K, Schwartz RP, O'Grady KE, Fitzgerald TT, et al. Initiating buprenorphine treatment prior to versus after release from prison: arrest outcomes. Drug and Alcohol Dependence 2018;188:232-8. [DOI: ] - PMC - PubMed
Gordon 2019 {published data only}
    1. Gordon MS, Vocci FJ, Taxman F, Fishman M, Sharma B, Blue TR, et al. A randomized controlled trial of buprenorphine for probationers and parolees: bridging the gap into treatment. Contemporary Clinical Trials 2019;79:21-7. [DOI: ] - PMC - PubMed
Gossop 2001 {published data only}
    1. Gossop M, Marsden J, Stewart D, Treacy S. Outcomes after methadone maintenance and methadone reduction treatments: two-year follow-up results from the National Treatment Outcome Research Study. Drug and Alcohol Dependence 2001;62(3):255-64. - PubMed
Gruber 2008 {published data only}
    1. Gruber VA, Delucchi KL, Kielstein A, Batki SL. A randomized trial of 6-month methadone maintenance with standard or minimal counseling versus 21-day methadone detoxification. Drug and Alcohol Dependence 2008;94:199-206. - PMC - PubMed
Haight 2019 {published data only}
    1. Haight BR, Learned SM, Laffont CM, Fudala PJ, Zhao Y, Garofalo AS, et al. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2019;393(10173):778-90. [DOI: 10.1016/S0140-6736(18)32259-1] - DOI - PubMed
Hoffmann 2014 {published data only}
    1. Hoffmann O, Frisell F, Ljungberg T. Better efficacy of buprenorphine and methadone in opioid dependence. Requirements for abstinence from non-opioids before starting treatment paid off [Battre effekt av buprenorfin och metadon vid opiatberoende. Krav pa drogfrihet fran icke-opioider fore behandlingsstart gav resultat]. Lakartidningen 2014;111(5):147-9. - PubMed
Johnson 1992 {published data only}
    1. Johnson RE, Jaffe JH, Fudala PJ. A controlled trial of buprenorphine treatment for opioid dependence. JAMA 1992;267(20):2750-5. - PubMed
Johnson 1995 {published data only}
    1. Johnson RE, Eissenberg T, Stitzer ML, Strain EC. A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. Drug and Alcohol Dependence. 1995;40(1):17-25. - PubMed
Johnson 2000 {published data only}
    1. Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. New England Journal of Medicine 2000;343(18):1290-7. - PubMed
    1. Marsch LA, Stephens MA, Mudric T, Strain EC, Bigelow GE, Johnson RE. Predictors of outcome in LAAM, buprenorphine, and methadone treatment for opioid dependence. Experimental and Clinical Psychopharmacology 2005;13(4):293-302. - PubMed
Kakko 2003 {published data only}
    1. Kakko J, Dybrandt Svanborg K, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet 2003;361(9358):662-8. - PubMed
Karp‐Gelernter 1982 {published data only}
    1. Karp-Gelernter E, Savage C, McCabe O. Evaluation of clinic attendance schedules for LAAM and methadone: a controlled study. International Journal of the Addictions 1982;17(5):805-13. - PubMed
Kelly 2020 {published data only}
    1. Kelly SM, Schwartz RP, O'Grady KE, Mitchell SG, Duren T, Sharma A, et al. Impact of methadone treatment initiated in jail on subsequent arrest. Journal of Substance Abuse Treatment 2020;113:108006. [DOI: ] - PMC - PubMed
Kim 2015 {published data only}
    1. Kim SJ, Marsch LA, Guarino H, Acosta MC, Aponte-Melendez Y. Predictors of outcome from computer-based treatment for substance use disorders: results from a randomized clinical trial. Drug and Alcohol Dependence 2015;157:174-8. [DOI: 10.1016/j.drugalcdep.2015.09.019] - DOI - PMC - PubMed
Kranzler 2021 {published data only}
    1. Kranzler HR, Lynch KG, Crist RC, Hartwell E, Le Moigne A, Laffont CM, et al. A delta-opioid receptor gene polymorphism moderates the therapeutic response to extended-release buprenorphine in opioid use disorder. International Journal of Neuropsychopharmacology 2021;24(2):89-96. - PMC - PubMed
Kristensen 2005 {published and unpublished data}
    1. Kristensen O, Espegren O, Asland R, Jakobsen E, Lie O, Seiler S. Buprenorphine and methadone to opiate addicts – a randomized trial. Tidsskrift for den Norske Laegeforening 2005;125(2):148-51. - PubMed
Kunøe 2016 {published and unpublished data}
    1. Kunøe N, Opheim A, Solli KK, Gaulen Z, Sharma-Haase K, Latif ZE, et al. Design of a randomized controlled trial of extended-release naltrexone versus daily buprenorphine-naloxone for opioid dependence in Norway (NTX-SBX). BMC Pharmacology and Toxicology 2016;17:1. [DOI: 10.1186/s40360-016-0061-1] - DOI - PMC - PubMed
Laffont 2018 {published and unpublished data}
    1. Laffont C, Ngaimisi E, Gopalakrishnan M, Young M, Haight B, Learned S, et al. Predictors of retention in treatment for opioid use disorder following administration of RBP-6000 vs. placebo. American Journal on Addictions 2018;27(4):328. [DOI: ]
Latif 2019a {published and unpublished data}
    1. Latif ZE, Solli KK, Opheim A, Kunoe N, Benth JŠ, Krajci P, et al. No increased pain among opioid-dependent individuals treated with extended-release naltrexone or buprenorphine-naloxone: a 3-month randomized study and 9-month open-treatment follow-up study. American Journal on Addictions 2019;28:77-85. - PubMed
Latif  2019b {published and unpublished data}
    1. Latif ZE, Šaltyte Benth J, Solli KK, Opheim A, Kunoe N, Krajci P, et al. Anxiety, depression, and insomnia among adults with opioid dependence treated with extended-release naltrexone vs buprenorphine-naloxone: a randomized clinical trial and follow-up study. JAMA Psychiatry 2018;76(2):127-34. [DOI: ] - PMC - PubMed
Liebschutz 2013 {published and unpublished data}
    1. Liebschutz JM, Crooks D, Herman DS, Anderson BJ, Meshesha L, Dossabhoy S, et al. Initiating buprenorphine maintenance for opiate-dependent hospitalized patients: a randomized controlled trial. Journal of General Internal Medicine 2013;28:S108-9.
Ling 1996 {published and unpublished data}
    1. Ling W, Wesson DR, Charuvastra C, Klett CJ. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Archives of General Psychiatry 1996;53(5):401-7. - PubMed
Ling 1998 {published and unpublished data}
    1. Ling W, Charuvastra C, Collins JF, Batki S, Brown LS Jr, Kintaudi P, et al. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction 1998;93(4):475-86. - PubMed
Ling 2010 {published data only}
    1. Beebe KL, Chavoustie S, Ling W, Sigmon S, Leiderman D, Bailey G. Buprenorphine implants for the treatment of opioid dependence: six and 12 month outcomes. Neuropsychopharmacology 2012;38:S266-7.
    1. Ling W, Casadonte P, Bigelow G, Kampman KM, Patkar A, Bailey GL, et al. Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial. JAMA 2010;304:1576-83. - PubMed
Ling 2019 {published data only}
    1. Ling W, Nadipelli VR, Solem CT, Ronquest NA, Yeh YC, Learned SM, et al. Patient-centered outcomes in participants of a buprenorphine monthly depot (BUP-XR) double-blind, placebo-controlled, multicenter, phase 3 study. Journal of Addiction Medicine 2019;13:442-9. [DOI: 10.1097/ADM.0000000000000517] - DOI - PMC - PubMed
Longshore 2005 {published and unpublished data}
    1. Longshore D, Annon J, Anglin MD, Rawson RA. Levo-alpha-acetylmethadol (LAAM) versus methadone: treatment retention and opiate use. Addiction 2005;100(8):1131-9. - PubMed
Maremmani 1999 {published data only}
    1. Maremmani I, Pani PP, Tagliamonte A, Gessa GL. Buprenorphine vs methadone: an Italian multicenter study. Giornale Italiano di Farmacia Clinica 1999;13(4):212-7.
Marsch 2016 {published data only}
    1. Marsch LA, Moore SK, Borodovsky JT, Solhkhah R, Badger GJ, Semino S, et al. A randomized controlled trial of buprenorphine taper duration among opioid-dependent adolescents and young adults. Addiction 2016;111(8):1406-15. [DOI: 10.1111/add.13363] - DOI - PMC - PubMed
McKenzie 2012 {published data only}
    1. McKenzie M, Zaller N, Dickman SL, Green TC, Parihk A, Friedmann PD, et al. A randomized trial of methadone initiation prior to release from incarceration. Substance Abuse 2012;33(1):19-29. - PMC - PubMed
Mokri 2016 {published data only}
    1. Mokri A, Chawarski MC, Taherinakhost H, Schottenfeld RS. Medical treatments for opioid use disorder in Iran: a randomized, double-blind placebo-controlled comparison of buprenorphine/naloxone and naltrexone maintenance treatment. Addiction 2016;111(5):874-82. [DOI: 10.1111/add.13259] - DOI - PubMed
Montoya 2004 {published data only}
    1. Montoya ID, Gorelick DA, Preston KL, Schroeder JR, Umbricht A, Cheskin LJ, et al. Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence. Clinical Pharmacology and Therapeutics 2004;75(1):34-8. - PMC - PubMed
Ngaimisi 2017 {published data only}
    1. Ngaimisi E, Gopalakrishnan M, Ivaturi V, Zhang W, Young M, Laffont CM. Exposure-response analyses to support dosing recommendations for RBP-6000 buprenorphine monthly formulation in subjects with opioid use disorder. Journal of Pharmacokinetics and Pharmacodynamics 2017;44:S50. [DOI: ]
Oleskowicz 2021 {published data only}
    1. Oleskowicz TN, Ochalek TA, Peck KR, Badger GJ, Sigmon SC. Within-subject evaluation of interim buprenorphine treatment during waitlist delays. Drug and Alcohol Dependence 2021;220:108532. [DOI: 10.1016/j.drugalcdep.2021.108532] - DOI - PMC - PubMed
Petitjean 2001 {published data only}
    1. Petitjean S, Stohler R, Deglon JJ, Livoti S, Waldvogel D, Uehlinger C, et al. Double-blind randomized trial of buprenorphine and methadone in opiate dependence. Drug and Alcohol Dependence 2001;62(1):97-104. - PubMed
Piralishvili 2015 {published data only}
    1. Piralishvili G, Otiashvili D, Sikharulidze Z, Kamkamidze G, Poole S, Woody GE. Opioid addicted buprenorphine injectors: drug use during and after 12-weeks of buprenorphine-naloxone or methadone in the Republic of Georgia. Journal of Substance Abuse Treatment 2015;50:32-7. - PubMed
Raleigh 2017 {published data only}
    1. Raleigh MF. Buprenorphine maintenance vs. placebo for opioid dependence. American Family Physician 2017;95(5):291A-B. - PubMed
Reimer 2011 {published data only}
    1. Reimer J, Verthein U, Karow A, Schäfer I, Naber D, Haasen C. Physical and mental health in severe opioid-dependent patients within a randomized controlled maintenance treatment trial. Addiction 2011;106(9):1647-55. - PubMed
Robertson 2006 {published data only}
    1. Robertson JR, Raab GM, Bruce M, McKenzie JS, Storkey HR, Salter A. Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: a randomized controlled trial. Addiction 2006;101(12):1752-9. - PubMed
Rosenthal 2013 {published data only}
    1. Rosenthal RN, Ling W, Casadonte P, Vocci F, Bailey GL, Kampman K, et al. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction 2013;108:2141-9. - PMC - PubMed
Sees 2000 {published data only}
    1. Sees KL, Delucchi KL, Masson C, Rosen A, Clark HW, Robillard H, et al. Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial. JAMA 2000;283(10):1303-10. - PubMed
    1. Sees KL, Delucchi KL, Reilly PM, Tusel DJ, Banys P, Clark HW. Attrition from a randomized trial comparing psychosocial treatments in a 180-day methadone detoxification clinic. NIDA Research Monograph Series 1993;132:202.
Shava 2018 {published data only}
    1. Shava E, Lipira LE, Beauchamp GG, Donnell DJ, Lockman S, Ruan Y, et al. Risky sexual behavior among individuals receiving buprenorphine/naloxone opiate dependency treatment: HIV prevention trials network (HPTN) 058. Journal of Acquired Immune Deficiency Syndromes 2018;78(3):300-7. [DOI: 10.1097/QAI.0000000000001683] - DOI - PMC - PubMed
Sigmon 2013 {published data only}
    1. Sigmon SC, Dunn KE, Saulsgiver K, Patrick ME, Badger GJ, Heil SH, et al. A randomized, double-blind evaluation of buprenorphine taper duration in primary prescription opioid abusers. JAMA Psychiatry 2013;70(12):1347-54. - PMC - PubMed
Sigmon 2015 {published data only}
    1. Sigmon SC, C Meyer A, Hruska B, Ochalek T, Rose G, Badger GJ, et al. Interim buprenorphine treatment: leveraging technology to bridge waitlist delays. Drug and Alcohol Dependence 2015;156:e204. [DOI: ]
Sigmon 2016 {published data only}
    1. Sigmon SC, Ochalek TA, Meyer AC, Hruska B, Heil SH, Badger GJ, et al. Interim buprenorphine vs. waiting list for opioid dependence. New England journal of Medicine 2016;375(25):2504-5. [DOI: ] - PMC - PubMed
Solli 2018a {published and unpublished data}
    1. Solli KK, Latif ZE, Opheim A, Krajci P, Sharma-Haase K, Benth JŠ, et al. Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial. Addiction 2018;113(10):1840-9. [DOI: ] - PubMed
Solli 2018b {published and unpublished data}
    1. Solli K, Opheim A, Latif ZE, Kunoe N, Tanum L. The effectiveness of injectable extended release naltrexone versus daily buprenorphine-naloxone for opioid dependence: a randomized clinical trial. Neurology 2018;90(Suppl 1):15.
Solli 2019 {published data only}
    1. Solli KK, Kunoe N, Latif ZE, Sharma-Haase K, Opheim A, Krajci P, et al. Availability of extended-release naltrexone may increase the number of opioid-dependent individuals in treatment: extension of a randomized clinical trial. European Addiction Research 2019;25(6):303-9. [DOI: ] - PubMed
Stein 2020 {published data only}
    1. Stein M, Herman D, Conti M, Anderson B, Bailey G. Initiating buprenorphine treatment for opioid use disorder during short-term in-patient 'detoxification': a randomized clinical trial. Addiction 2020;115(1):82-94. [DOI: ] - PubMed
Stitzer 1983 {published data only}
    1. Stitzer ML, McCaul ME, Bigelow GE, Liebson I. Treatment outcome in methadone detoxification: relationship to initial levels of illicit opiate use. Drug and Alcohol Dependence 1983;12(3):259-67. - PubMed
Strain 1996 {published data only}
    1. Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Buprenorphine versus methadone in the treatment of opioid dependence: self-reports, urinalysis, and addiction severity index. Journal of Clinical Psychopharmacology 1996;16(1):58-67. - PubMed
Strang 2000 {published data only}
    1. Strang J, Marsden J, Cummins M, Farrell M, Finch E, Gossop M, et al. Randomized trial of supervised injectable versus oral methadone maintenance: report of feasibility and 6-month outcome. Addiction 2000;95(11):1631-45. - PubMed
Streck 2018 {published data only}
    1. Streck JM, Ochalek TA, Badger GJ, Sigmon SC. Interim buprenorphine treatment during delays to comprehensive treatment: changes in psychiatric symptoms. Experimental and Clinical Psychopharmacology 2018;26(4):403-9. [DOI: ] - PMC - PubMed
Tanum 2017a {published and unpublished data}
    1. Tanum L, Solli KK, Latif ZE, Benth JŠ, Opheim A, Sharma-Haase K, et al. Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: a randomized clinical noninferiority trial. JAMA Psychiatry 2017;74(12):1197-205. [DOI: ] - PMC - PubMed
Tanum 2017b {published and unpublished data}
    1. Tanum L. Effectiveness of extended release naltrexone versus daily buprenorphine-naloxone for opioid dependence-Norway trial. Neuropsychopharmacology 2017;43(Suppl 1):S61. [DOI: ]
Tanum 2017c {published data only}
    1. Tanum LH, Opheim A, Solli K, Sharma-Haase K, Latif ZE, Kunoe N. Optimal prevention of relapse among opioid users: a 12-week randomized controlled trial of extended-release naltrexone injections versus daily buprenorphine-naloxone. Drug and Alcohol Dependence 2017;171:e200-1. [DOI: ]
Tanum 2018a {published data only}
    1. Tanum L, Solli K, Latif ZE, Benth JS, Opheim A, Krajci P, et al. The effectiveness of injectable extended release naltrexone versus daily buprenorphine-naloxone for opioid dependence in short and long term treatment. Biological Psychiatry 2018;83( 9 Suppl):S454.
Tanum 2018b {published data only}
    1. Tanum L, Solli KK, Latif Z, Benth JS, Opheim A, Sharma-Haase K, et al. "Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: a randomized clinical noninferiority trial": correction. JAMA Psychiatry 2018;75(5):530. - PMC - PubMed
Tanum 2018c {published and unpublished data}
    1. Tanum L, Klemmetsby SK. Use of benzodiazepines among opioid dependent individuals during a 12 week randomized study and a 36-week follow-up study with extended release naltrexone. Heroin Addiction and Related Clinical Problems 2018;20(Suppl 2):28.
Tanum 2019 {published data only}
    1. Tanum L, Latif ZE, Solli K, Opheim A, Kunoe N, Benth J, et al. No increase in chronic pain among opioid-dependent individuals randomized to treatment with extended-release naltrexone compared to buprenorphine-naloxone. Biological Psychiatry 2019;85(Suppl):S211-2. [DOI: ]
Tennant 1982 {published data only}
    1. Tennant FS Jr, Rawson RA. Outpatient treatment of prescription opioid dependence: comparison of two methods. Archives of Internal Medicine 1982;142(10):1845-7. - PubMed
Uehlinger 1998 {published data only}
    1. Uehlinger C, Deglon J, Livoti S, Petitjean S, Waldvogel D, Ladewig D. Comparison of buprenorphine and methadone in the treatment of opioid dependence. Swiss multicentre study. European Addiction Research 1998;4(S1):13-8. - PubMed
Wang 2019 {published data only}
    1. Wang X, Jiang H, Zhao M, Li J, Gray F, Sheng L, et al. Treatment of opioid dependence with buprenorphine/naloxone sublingual tablets: a phase 3 randomized, double-blind, placebo-controlled trial. Asia-Pacific Psychiatry 2019;11(1):e12344. [DOI: 10.1111/appy.12344] - DOI - PubMed
Watkins 2017 {published data only}
    1. Watkins KE, Ober AJ, Lamp K, Lind M, Setodji C, Osilla KC, et al. Collaborative care for opioid and alcohol use disorders in primary care: the SUMMIT randomized clinical trial. JAMA Internal Medicine 2017;177(10):1480-8. [DOI: 10.1001/jamainternmed.2017.3947] - DOI - PMC - PubMed
Weiss 2011 {published data only}
    1. Weiss R, Potter JS, Feillin DA, Byrne M, Connery HS, Dickinson W, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence. Archives of General Psychiatry 2011;68(12):1238-46. - PMC - PubMed

References to ongoing studies

Gordon 2021 {published data only}
    1. Gordon MS, Mitchell SG, Blue TR, Vocci FJ, Fishman MJ, Murphy SM, et al. A clinical protocol of a comparative effectiveness trial of extended-release naltrexone versus extended-release buprenorphine with individuals leaving jail. Journal of Substance Abuse Treatment 2021;128:108241. [DOI: DOI: 10.1016/j.jsat.2020.108241] - PMC - PubMed
Seval 2021 {published data only}
    1. Seval N, Frank CA, Litwin AH, Roth P, Schade MA, Pavlicova M, et al. Design and methods of a multi-site randomized controlled trial of an integrated care model of long-acting injectable buprenorphine with infectious disease treatment among persons hospitalized with infections and opioid use disorder. Contemporary Clinical Trials 2021;105:106394. [DOI: ] - PMC - PubMed
Socias 2018 {published data only}
    1. Socias ME, Ahamad K, Le Foll B, Lim R, Bruneau J, Fischer B, et al. The OPTIMA study, buprenorphine/naloxone and methadone models of care for the treatment of prescription opioid use disorder: study design and rationale. Contemporary Clinical Trials 2018;69:21-7. [DOI: 10.1016/j.cct.2018.04.001] - DOI - PMC - PubMed

Additional references

Amass 2000
    1. Amass L, Kamien JB, Mikulich SK. Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Drug and Alcohol Dependence 2000;58(1-2):143-52. [PMID: ] - PubMed
Amato 2005
    1. Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP. An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment 2005;28(4):321-9. [PMID: ] - PubMed
Auriacombe 2001
    1. Auriacombe M, Franques P, Tignol J. Deaths attributable to methadone vs buprenorphine in France. JAMA 2001;285(1):45. [PMID: ] - PubMed
Australian Institute of Health and Welfare 2018
    1. Australian Institute of Health and Welfare. Opioid harm in Australia: and comparisons between Australia and Canada, 2018. nla.gov.au/nla.obj-2312926122/view (accessed 19 July 2022).
Banta‐Green 2009
    1. Banta-Green CJ, Maynard C, Koepsell TD, Wells EA, Donovan DM. Retention in methadone maintenance drug treatment for prescription-type opioid primary users compared to heroin users. Addiction 2009;104:775-83. - PubMed
Belzak 2018
    1. Belzak L, Halverson J. The opioid crisis in Canada: a national perspective. Health Promotion and Chronic Disease Prevention in Canada : Research, Policy and Practice 2018;38(6):224-33. - PMC - PubMed
Brands 2004
    1. Brands B, Blake J, Sproule B, Gourlay D, Busto U. Prescription opioid abuse in patients presenting for methadone maintenance treatment. Drug and Alcohol Dependence 2004;73:199-207. - PubMed
Bruneau 2018
    1. Bruneau J, Ahamad K, Goyer M, Poulin G, Selby P, Fischer B, et al. Management of opioid use disorders: a national clinical practice guideline. CMAJ : Canadian Medical Association Journal 2018;190(9):E247-57. - PMC - PubMed
Campbell 2015
    1. Campbell G, Nielsen S, Larance B, Bruno R, Mattick R, Hall W, et al. Pharmaceutical opioid use and dependence among people living with chronic pain: associations observed within the pain and opioids in treatment (POINT) cohort. Pain Medicine 2015;16(9):1745-58. - PubMed
Caplehorn 1996
    1. Caplehorn JR, Dalton MS, Haldar F, Petrenas AM, Nisbet JG. Methadone maintenance and addicts' risk of fatal heroin overdose. Substance Use & Misuse 1996;31(2):177-96. [PMID: ] - PubMed
Chenaf 2019
    1. Chenaf C, Kaboré JL, Delorme J, Pereira B, Mulliez A, Zenut M, et al. Prescription opioid analgesic use in France: trends and impact on morbidity–mortality. European Journal of Pain 2019;23(1):124-34. - PubMed
Chou 2015
    1. Chou R, Turner J, Devine E, Hansen R, Sullivan S, Blazina I, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Annals of Internal Medicine 2015;162(4):276-86. - PubMed
Clark 2002
    1. Clark N, Lintzeris N, Gijsbers A, Whelan G, Dunlop A, Ritter A, et al. LAAM maintenance vs methadone maintenance for heroin dependence. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No: CD002210. [DOI: 10.1002/14651858.CD002210] - DOI - PubMed
Cleeland 1991
    1. Cleeland C. The Brief Pain Inventory (BPI), 1991. www.mdanderson.org/documents/Departments-and-Divisions/Symptom-Research/... (accessed 19 July 2022).
Cragg 2019
    1. Cragg A, Hau J, Woo S, Kitchen S, Liu C, Doyle-Waters M, et al. Risk factors for misuse of prescribed opioids: a systematic review and meta-analysis. Annals of Emergency Medicine 2019;74(5):634-46. - PubMed
Deeks 2022
    1. Deeks JJ, Higgins JP, Altman DG. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Degenhardt 2007
    1. Degenhardt L, Larance B, Mathers B, Azim T, Kamarulzaman A, Mattick R, et al, Reference Group to the United Nations on HIV and Injecting Drug Use. Benefits and risks of pharmaceutical opioids: essential treatment and diverted medication. A global review of availability, extra-medical use, injection and the association with HIV. www.unodc.org/documents/hiv-aids/publications/Benefits_and_risks_of_phar... (accessed prior to 19 July 2022). [ISBN 978-0-7334-2707-7]
Degenhardt 2009
    1. Degenhardt L, Randall D, Hall W, Law M, Butler T, Burns L. Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: risk factors and lives saved. Drug and Alcohol Dependence 2009;105(1-2):9-15. [PMID: ] - PubMed
Degenhardt 2019
    1. Degenhardt L, Grebely J, Stone J, Hickman M, Vickerman P, Marshall BD, et al. Global patterns of opioid use and dependence: harms to populations, interventions, and future action. Lancet 2019;394(10208):1560-79. - PMC - PubMed
Ellerstrand 2017
    1. Ellerstrand J, Ferrari A, Degenhardt L, Whiteford H, Leung J. A systematic review of the global prevalence of prescription opioid non-medical use with an estimate of prescription opioid dependence. NDARC Technical Report No. 337. ndarc.med.unsw.edu.au/resource/systematic-review-global-prevalence-presc... (accessed prior to 19 July 2022).
Faggiano 2003
    1. Faggiano F, Vigna-Taglianti F, Versino E, Lemma P. Methadone maintenance at different dosages for opioid dependence. Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No: CD002208. [DOI: 10.1002/14651858.CD002208] - DOI - PubMed
Fischer 2008
    1. Fischer B, Patra J, Cruz MF, Gittins J, Rehm J. Comparing heroin users and prescription opioid users in a Canadian multi-site population of illicit opioid users. Drug and Alcohol Review 2008;27:625-32. - PubMed
Fischer 2012
    1. Fischer B, Argento E. Prescription opioid related misuse, harms, diversion and interventions in Canada: a review. Pain Physician 2012;15(3 Suppl):ES191-203. [PMID: ] - PubMed
Gowing 2011
    1. Gowing L, Farrell MF, Bornemann R, Sullivan LE, Ali R. Oral substitution treatment of injecting opioid users for prevention of HIV infection. Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No: CD004145. [DOI: 10.1002/14651858.CD004145.pub4] - DOI - PubMed
Gowing 2012
    1. Gowing LR. The role of opioid substitution treatment in reducing HIV transmission. BMJ 2012;345:e6425. - PubMed
Gowing 2013
    1. Gowing LR, Hickman M, Degenhardt L. Mitigating the risk of HIV infection with opioid substitution treatment. Bulletin of the World Health Organization 2013;91:148-9. - PMC - PubMed
GRADE 2004
    1. The GRADE working group. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490-4. - PMC - PubMed
Grella 2011
    1. Grella CE, Lovinger K. 30-year trajectories of heroin and other drug use among men and women sampled from methadone treatment in California. Drug and Alcohol Dependence 2011;118(2-3):251-8. [PMID: ] - PMC - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7560):924-6. - PMC - PubMed
Guyatt 2011
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines 1. Introduction – GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64:383-94. - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2022
    1. Higgins JP, Li T, Deeks JJ. Chapter 6: Choosing effect measures and computing estimates of effect. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Hser 2001
    1. Hser YI, Hoffman V, Grella CE, Anglin MD. A 33-year follow-up of narcotics addicts. Archives of General Psychiatry 2001;58(5):503-8. [PMID: ] - PubMed
Kessler 2002
    1. Kessler RC, Andrews G, Colpe LJ, Hiripi E, Mroczek DK, Normand SL, et al. Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychological Medicine 2002;32:959-76. - PubMed
Klimas 2019a
    1. Klimas J, Gorfinkel L, Fairbairn N, Amato L, Ahamad K, Nolan S, et al. Strategies to identify patient risks of prescription opioid addiction when initiating opioids for pain: a systematic review. JAMA Network Open 2019;2:e193365. [DOI: 10.1001/jamanetworkopen.2019.3365] - DOI - PMC - PubMed
Klimas 2019b
    1. Klimas J, Gorfinkel L, Giacomuzzi SM, Ruckes C, Socías ME, Fairbairn N, et al. Slow release oral morphine versus methadone for the treatment of opioid use disorder. BMJ Open 2019;9:e025799. [DOI: 10.1136/bmjopen-2018-025799] - DOI - PMC - PubMed
Lam 2020
    1. Lam T, Kuhn L, Hayman J, Middleton M, Wilson J, Scott D, et al. Recent trends in heroin and pharmaceutical opioid-related harms in Victoria, Australia up to 2018. Addiction 2020;115(2):261-9. - PubMed
Larney 2020
    1. Larney S, Tran L, Leung J, Santo T, Santomauro D, Hickman M, et al. All-cause and cause-specific mortality among people using extramedical opioids: a systematic review and meta-analysis. JAMA Psychiatry 2020;77(5):493-502. - PMC - PubMed
Lefebvre 2022
    1. Lefebvre C, Glanville J, Briscoe S, Featherstone R, Littlewood A, Marshall C, et al. Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Li 2022
    1. Li T, Higgins JP, Deeks JJ. Chapter 5: Collecting data. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Lovibond 1995
    1. Lovibond SH, Lovibond PF. Manual for Depression and Anxiety Stress Scales. 2nd edition. Sydney (Australia): Psychology Foundation, 1995.
Lusted 2013
    1. Lusted A, Roerecke M, Goldner E, Rehm J, Fischer B. Prevalence of pain among non-medical prescription opioid users in substance use treatment populations: systematic review and meta-analyses. Pain Physician 2013;16:E671-84. - PubMed
MacArthur 2012
    1. MacArthur GJ, Minozzi S, Martin N, Vickerman P, Deren S, Bruneau J, et al. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ (Clinical Research Ed.) 2012;345:e5945. [PMID: ] - PMC - PubMed
Man 2021
    1. Man N, Chrzanowska A, Sutherland R, Degenhardt L, Peacock A. Trends in drug-related hospitalisations in Australia, 1999–2019. Drug Trends Bulletin Series. ndarc.med.unsw.edu.au/resource-analytics/trends-drug-related-hospitalisa... (accessed prior to 19 July 2022). [DOI: ]
Mattick 2009
    1. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No: CD002209. [DOI: 10.1002/14651858.CD002209.pub2] - DOI - PMC - PubMed
Mattick 2014
    1. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No: CD002207. [DOI: 10.1002/14651858.CD002207.pub4] - DOI
Mattson 2021
    1. Mattson CL, Tanz LJ, Quinn K, Kariisa M, Patel P, Davis NL. Trends and geographic patterns in drug and synthetic opioid overdose deaths – United States, 2013–2019. Morbidity and Mortality Weekly Report 2021;70:202-7. [DOI: ] - PMC - PubMed
McCabe 2013
    1. McCabe BE, Santisteban DA, Mena MP, Duchene DM, McLean C, Monroe M. Engagement, retention, and abstinence for three types of opioid users in Florida. Substance Use & Misuse 2013;48:623-34. - PMC - PubMed
Melzack 1975
    1. Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain 1975;1:277-99. - PubMed
Moore 2007
    1. Moore BA, Fiellin DA, Barry DT, Sullivan LE, Chawarski MC, O'Connor PG, et al. Primary care office-based buprenorphine treatment: comparison of heroin and prescription opioid dependent patients. Journal of General Internal Medicine 2007;22:527-30. - PMC - PubMed
Nielsen 2011
    1. Nielsen S, Cameron J, Lee N. Characteristics of a non-treatment seeking sample of over-the-counter codeine users: implications for intervention and prevention. Journal of Opioid Management 2011;7:363-70. - PubMed
Nielsen 2013
    1. Nielsen S, Hillhouse M, Thomas C, Hasson A, Ling W. A comparison of buprenorphine taper outcomes between prescription opioid and heroin users. Journal of Addiction Medicine 2013;7:33-8. - PMC - PubMed
Nielsen 2015a
    1. Nielsen S, Roxburgh A, Bruno R, Lintzeris N, Jefferson A, Degenhardt L. Changes in non-opioid substitution treatment episodes for pharmaceutical opioids and heroin from 2002 to 2011. Drug and Alcohol Dependence 2015;149:212-9. - PubMed
Nielsen 2015b
    1. Nielsen S, Hillhouse M, Mooney L, Ang A, Ling W. Buprenorphine pharmacotherapy and behavioral treatment: comparison of outcomes among prescription opioid users, heroin users and combination users. Journal of Substance Abuse Treatment 2015;48:70-6. - PMC - PubMed
Padaiga 2007
    1. Padaiga Z, Subata E, Vanagas G. Outpatient methadone maintenance treatment program. Quality of life and health of opioid-dependent persons in Lithuania. Medicina (Kaunas, Lithuania) 2007;43(3):235-41. [PMID: ] - PubMed
Review Manager Web [Computer program]
    1. Review Manager Web (RevMan Web). The Cochrane Collaboration, 2022. Available at: revman.cochrane.org.
Schünemann 2021
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing 'Summary of findings' tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Sordo 2017
    1. Sordo L, Barrio G, Bravo M, Indave I, Degenhardt L, Wiessing L, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ 2017;357:j1550. - PMC - PubMed
Turk 2008
    1. Turk DC, Dworkin RH, McDermott MP, Bellamy N, Burke LB, Chandler JM, et al. Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. Pain 2008;139:485-93. - PubMed
Voon 2017
    1. Voon P, Karamouzian M, Kerr T. Chronic pain and opioid misuse: a review of reviews. Substance Abuse Treatment, Prevention, and Policy 2017;12 (1):36. [DOI: 10.1186/s13011-017-0120-7] - DOI - PMC - PubMed
Vowles 2015
    1. Vowles K, McEntee ML, Julnes P, Frohe T, Ney J, Goes D. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 2015;156(4):569-76. - PubMed
Walsh 1994
    1. Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clinical Pharmacology and Therapeutics 1994;55(5):569-80. [PMID: ] - PubMed
Ware 1992
    1. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care 1992;30:473-83. - PubMed
WHO 1997
    1. World Health Organization. WHOQOL: Measuring Quality of Life. Geneva (Switzerland): World Health Organization, 1997.
WHO 2004
    1. World Health Organization. ICD-10: international statistical classification of diseases and related health problems: tenth revision, 2004. apps.who.int/iris/handle/10665/42980 (accessed 19 July 2022).
WHO 2009
    1. World Health Organization. Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. Geneva (Switzerland): World Health Organization, 2009. [ISBN 978 92 4 154754 3] - PubMed

References to other published versions of this review

Nielsen 2016
    1. Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database of Systematic Reviews 2016, Issue 5. Art. No: CD011117. [DOI: 10.1002/14651858.CD011117.pub2] - DOI - PubMed

Publication types

MeSH terms

Associated data