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
Meta-Analysis
. 2014 Feb 6;2014(2):CD002207.
doi: 10.1002/14651858.CD002207.pub4.

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

Richard P Mattick  1 , Courtney Breen, Jo Kimber, Marina Davoli
Affiliations
Meta-Analysis

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

Richard P Mattick et al. Cochrane Database Syst Rev. .

Abstract

Background: Buprenorphine maintenance treatment has been evaluated in randomised controlled trials against placebo medication, and separately as an alternative to methadone for management of opioid dependence.

Objectives: To evaluate buprenorphine maintenance compared to placebo and to methadone maintenance in the management of opioid dependence, including its ability to retain people in treatment, suppress illicit drug use, reduce criminal activity, and mortality.

Search methods: We searched the following databases to January 2013: Cochrane Drugs and Alcohol Review Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents, PsycLIT, CORK, Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library of Congress, reference lists of identified studies and reviews. We sought published/unpublished randomised controlled trials (RCTs) from authors.

Selection criteria: Randomised controlled trials of buprenorphine maintenance treatment versus placebo or methadone in management of opioid-dependent persons.

Data collection and analysis: We used Cochrane Collaboration methodology.

Main results: We include 31 trials (5430 participants), the quality of evidence varied from high to moderate quality.There is high quality of evidence that buprenorphine was superior to placebo medication in retention of participants in treatment at all doses examined. Specifically, buprenorphine retained participants better than placebo: at low doses (2 - 6 mg), 5 studies, 1131 participants, risk ratio (RR) 1.50; 95% confidence interval (CI) 1.19 to 1.88; at medium doses (7 - 15 mg), 4 studies, 887 participants, RR 1.74; 95% CI 1.06 to 2.87; and at high doses (≥ 16 mg), 5 studies, 1001 participants, RR 1.82; 95% CI 1.15 to 2.90. However, there is moderate quality of evidence that only high-dose buprenorphine (≥ 16 mg) was more effective than placebo in suppressing illicit opioid use measured by urinanalysis in the trials, 3 studies, 729 participants, standardised mean difference (SMD) -1.17; 95% CI -1.85 to -0.49, Notably, low-dose, (2 studies, 487 participants, SMD 0.10; 95% CI -0.80 to 1.01), and medium-dose, (2 studies, 463 participants, SMD -0.08; 95% CI -0.78 to 0.62) buprenorphine did not suppress illicit opioid use measured by urinanalysis better than placebo.There is high quality of evidence that buprenorphine in flexible doses adjusted to participant need,was less effective than methadone in retaining participants, 5 studies, 788 participants, RR 0.83; 95% CI 0.72 to 0.95. For those retained in treatment, no difference was observed in suppression of opioid use as measured by urinalysis, 8 studies, 1027 participants, SMD -0.11; 95% CI -0.23 to 0.02 or self report, 4 studies, 501 participants, SMD -0.11; 95% CI -0.28 to 0.07, with moderate quality of evidence.Consistent with the results in the flexible-dose studies, in low fixed-dose studies, methadone (≤ 40 mg) was more likely to retain participants than low-dose buprenorphine (2 - 6 mg), (3 studies, 253 participants, RR 0.67; 95% CI: 0.52 to 0.87). However, we found contrary results at medium dose and high dose: there was no difference between medium-dose buprenorphine (7 - 15 mg) and medium-dose methadone (40 - 85 mg) in retention, (7 studies, 780 participants, RR 0.87; 95% CI 0.69 to 1.10) or in suppression of illicit opioid use as measured by urines, (4 studies, 476 participants, SMD 0.25; 95% CI -0.08 to 0.58) or self report of illicit opioid use, (2 studies, 174 participants, SMD -0.82; 95% CI -1.83 to 0.19). Similarly, there was no difference between high-dose buprenorphine (≥ 16 mg) and high-dose methadone (≥ 85 mg) in retention (RR 0.79; 95% CI 0.20 to 3.16) or suppression of self-reported heroin use (SMD -0.73; 95% CI -1.08 to -0.37) (1 study, 134 participants).Few studies reported adverse events ; two studies compared adverse events statistically, finding no difference between methadone and buprenorphine, except for a single result indicating more sedation among those using methadone.

Authors' conclusions: Buprenorphine is an effective medication in the maintenance treatment of heroin dependence, retaining people in treatment at any dose above 2 mg, and suppressing illicit opioid use (at doses 16 mg or greater) based on placebo-controlled trials.However, compared to methadone, buprenorphine retains fewer people when doses are flexibly delivered and at low fixed doses. If fixed medium or high doses are used, buprenorphine and methadone appear no different in effectiveness (retention in treatment and suppression of illicit opioid use); however, fixed doses are rarely used in clinical practice so the flexible dose results are more relevant to patient care. Methadone is superior to buprenorphine in retaining people in treatment, and methadone equally suppresses illicit opioid use.

PubMed Disclaimer

Conflict of interest statement

The first reviewer, RPM, is the first author on one trial of buprenorphine versus methadone for maintenance therapy in opioid dependence (see reference in the Included Studies). RPM has received untied educational funds from ReckittBenckiser for studies of post‐marketing surveillance of buprenorphine, to conduct research required by the Australian Government for the registration and/or subsidising of this medication for use in Australia. RPM has not received any personal income from ReckittBenckiser. There are no other declarations of interest.

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.
4
4
Forest plot of comparison: 1 Flexible dose buprenorphine versus flexible dose methadone, outcome: 1.1 Retention in treatment.
1.1
1.1. Analysis
Comparison 1 Flexible‐dose buprenorphine versus flexible‐dose methadone, Outcome 1 Retention in treatment.
1.2
1.2. Analysis
Comparison 1 Flexible‐dose buprenorphine versus flexible‐dose methadone, Outcome 2 Morphine‐positive urines.
1.3
1.3. Analysis
Comparison 1 Flexible‐dose buprenorphine versus flexible‐dose methadone, Outcome 3 Self‐reported heroin use.
1.4
1.4. Analysis
Comparison 1 Flexible‐dose buprenorphine versus flexible‐dose methadone, Outcome 4 Cocaine‐positive urines.
1.5
1.5. Analysis
Comparison 1 Flexible‐dose buprenorphine versus flexible‐dose methadone, Outcome 5 Benzodiazepine‐positive urines.
1.6
1.6. Analysis
Comparison 1 Flexible‐dose buprenorphine versus flexible‐dose methadone, Outcome 6 Criminal activity.
2.1
2.1. Analysis
Comparison 2 Low‐dose buprenorphine versus low‐dose methadone, Outcome 1 Retention in treatment.
2.2
2.2. Analysis
Comparison 2 Low‐dose buprenorphine versus low‐dose methadone, Outcome 2 Morphine‐positive urines.
2.3
2.3. Analysis
Comparison 2 Low‐dose buprenorphine versus low‐dose methadone, Outcome 3 Self‐reported heroin use.
2.4
2.4. Analysis
Comparison 2 Low‐dose buprenorphine versus low‐dose methadone, Outcome 4 Cocaine‐positive urines.
3.1
3.1. Analysis
Comparison 3 Medium‐dose buprenorphine versus medium‐dose methadone, Outcome 1 Retention in treatment.
3.2
3.2. Analysis
Comparison 3 Medium‐dose buprenorphine versus medium‐dose methadone, Outcome 2 Morphine‐positive urines.
3.3
3.3. Analysis
Comparison 3 Medium‐dose buprenorphine versus medium‐dose methadone, Outcome 3 Self‐reported heroin use.
3.4
3.4. Analysis
Comparison 3 Medium‐dose buprenorphine versus medium‐dose methadone, Outcome 4 Cocaine‐positive urines.
4.1
4.1. Analysis
Comparison 4 High‐dose buprenorphine versus high‐dose methadone, Outcome 1 Retention in treatment.
4.2
4.2. Analysis
Comparison 4 High‐dose buprenorphine versus high‐dose methadone, Outcome 2 Self‐reported heroin use.
5.1
5.1. Analysis
Comparison 5 Low‐dose buprenorphine versus placebo, Outcome 1 Retention in treatment.
5.2
5.2. Analysis
Comparison 5 Low‐dose buprenorphine versus placebo, Outcome 2 Morphine‐positive urines.
5.3
5.3. Analysis
Comparison 5 Low‐dose buprenorphine versus placebo, Outcome 3 Cocaine‐positive urines.
5.4
5.4. Analysis
Comparison 5 Low‐dose buprenorphine versus placebo, Outcome 4 Benzodiazepine‐positive urines.
6.1
6.1. Analysis
Comparison 6 Medium‐dose buprenorphine versus placebo, Outcome 1 Retention in treatment.
6.2
6.2. Analysis
Comparison 6 Medium‐dose buprenorphine versus placebo, Outcome 2 Morphine‐positive urines.
6.3
6.3. Analysis
Comparison 6 Medium‐dose buprenorphine versus placebo, Outcome 3 Cocaine‐positive urines.
6.4
6.4. Analysis
Comparison 6 Medium‐dose buprenorphine versus placebo, Outcome 4 Benzodiazepine‐positive urines.
7.1
7.1. Analysis
Comparison 7 High‐dose buprenorphine versus placebo, Outcome 1 Retention in treatment.
7.2
7.2. Analysis
Comparison 7 High‐dose buprenorphine versus placebo, Outcome 2 Morphine‐positive urines.
7.3
7.3. Analysis
Comparison 7 High‐dose buprenorphine versus placebo, Outcome 3 Cocaine‐positive urines.
7.4
7.4. Analysis
Comparison 7 High‐dose buprenorphine versus placebo, Outcome 4 Benzodiazepine‐positive urines.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Ahmadi 2002a {published data only}
    1. Ahmadi J. A controlled trial of buprenorphine treatment for opium dependence: The first experience from Iran. Drug and Alcohol Dependence 2002;66(2):111‐4. - PubMed
Ahmadi 2003a {published data only}
    1. Ahmadi J. Methadone versus buprenorphine maintenance for the treatment of heroin‐dependent outpatients. Journal of Substance Abuse Treatment 2003;24(3):217‐20. - PubMed
Ahmadi 2003b {published data only}
    1. Ahmadi J, Ahmadi K, Ohaeri J. Controlled, randomised trial in maintenance treatment of intravenous buprenorphine dependence with naltrexone, methadone or buprenorphine: A novel study. European Journal of Clinical Investigation 2003;33(9):824‐9. - PubMed
Ahmadi 2004 {published data only}
    1. Ahmadi J, Babaee‐Beigi M, Alishahi M, Maany I, Hidari T. Twelve‐month maintenance treatment of opium‐dependent patients. Journal of Substance Abuse Treatment 2004;26(1):61‐4. - PubMed
Fischer 1999 {published and unpublished data}
    1. Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger G, et al. Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Addiction 1999;94(9):1337‐47. - PubMed
Fudala 2003 {published and unpublished data}
    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
Johnson 1992 {published and unpublished data}
    1. Johnson R, Jaffe J, Fudala P. A controlled trial of buprenorphine treatment for opioid dependence. JAMA 1992;267(20):2750‐5. [MEDLINE: ] - PubMed
Johnson 1995a {published and unpublished data}
    1. Johnson RE, Eissenberg T, Stitzer ML, Strain EC, Liebson IA, Bigelow GE. A placebo controlled trial of buprenorphine as a treatment for opioid dependence. Drug and Alcohol Dependence 1995;40(1):17‐25. - PubMed
Johnson 2000 {published and unpublished data}
    1. Johnson RE, Chutuape MA, Strain, EC, Walsh SL, Stitzer ML, Begelow GE. A comparison of levomethadyl acetate, buprenorphine and methadone for opioid dependence. New England Journal of Medicine 2000;343(18):1290‐7. - PubMed
Kakko 2003 {published and unpublished data}
    1. Kakko J, Svanborg KD, 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
Kakko 2007 {published data only}
    1. Kakko J, Grönbladh L, Svanborg KD, Wachenfeldt J, Rück C, Rawlings B, et al. A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomised controlled trial. American Journal of Psychiatry 2007;164(5):797‐803. - PubMed
Kamien 2008 {published data only}
    1. Kamien JB, Branstetter SA, Amass L. Buprenorphine‐naloxone versus methadone maitenance therapy: A randomised double‐blind trial with opioid dependent patients. Heroin Addiction and Related Clinical Problems 2008;10(4):5‐18.
Kosten 1993 {published data only}
    1. Kosten T, Schottenfeld R, Ziedonis D, Falcioni J. Buprenorphine versus methadone maintenance for opioid dependence. Journal of Nervous and Mental Disease 1993;181(6):358‐64. [MEDLINE: ] - PubMed
Kristensen 2005 {published data only}
    1. Kristensen Ø, Espegren O, Asland R, Jakobsen E, Lie Ø, Seiler S. Buprenorphine and methadone to opiate addicts‐‐a randomized trial (English abstract only). Tidsskrift for den Norske Laegeforening 2005;125(2):148‐51. [PMID: 15665884] - PubMed
Krook 2002 {published data only}
    1. Krook AL, Brørs O, Dahlberg J, Grouff K, Magnus P, Røysamb E, et al. A placebo‐controlled study of high dose buprenorphine in opiate dependents waiting for medication‐assisted rehabilitation in Oslo, Norway. Addiction 2002;97(5):533‐42. - PubMed
Ling 1996 {published and unpublished data}
    1. Ling W, Wesson D, Charuvastra C, Klett J. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Archives of General Psychiatry 1996;53(5):401‐7. [MEDLINE: ] - 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, randomised clinical trial. Addiction 1998;93(4):475‐86. - PubMed
Ling 2010 {published data only}
    1. Ling W, Casadonte P, Beglow G, Kampman KM, Patkar A, Bailey GL, et al. Buprenorphine implants for treatment of opioid dependence: A randomized controlled trial. JAMA 2010;304(14):1576‐83. - PubMed
Lintzeris 2004 {published data only}
    1. Lintzeris N, Ritter A, Panjari M, Clark N, Kutin J, Bammer G. Implementing buprenorphine treatment in community settings in Australia: Experiences from the buprenorphine implementation trial. American Journal on Addictions 2004;13 Suppl 1:S29‐S41. - PubMed
Magura 2009 {published data only}
    1. Magura S, Lee JD, Hershberger J, Joseph H, Marsch L, Shropshire C, et al. Buprenorphine and methadone maintenance in jail and post‐release: A randomized clinical trial. Drug and Alcohol Dependence 2009;99(1‐3):222‐30. - PMC - PubMed
Mattick 2003 {published data only}
    1. Mattick RP, Ali R, White J, O'Brien S, Wolk S, Danz C. Buprenorphine versus methadone maintenance therapy: A randomised double‐blind with 405 opioid‐dependent patients. Addiction 2003;98(4):441‐52. - PubMed
Neri 2005 {published data only}
    1. Neri S, Bruno CM, Pulvirenti D, Malaguarnera M, Italiano C, Mauceri B, et al. Randomised clinical trial to compare the effects of methadone and buprenorphine on the immune system in drug abusers. Psychopharmacology 2005;179(3):700‐4. - PubMed
Oliveto 1999 {published data only}
    1. Oliveto AH, Feingold A, Schottenfeld R, Jatlow P, Kosten TR. Desipramine in opioid‐dependent cocaine abusers maintained on methadone or buprenorphine. Archives of General Psychiatry 1999;56(9):812‐20. - PubMed
Pani 2000 {published data only}
    1. Pani PP, Maremmani I, Pirastu R, Tagliamonte A, Gessa GL. Buprenorphine: A controlled trial in the treatment of opioid dependence. Drug and Alcohol Dependence 2000;60(1):39‐50. - PubMed
Petitjean 2001 {published and unpublished data}
    1. Petitjean S, Stohler R, Déglon JJ, Livoti S, Waldvogel D, Uehlinger C, et al. Double‐blind randomised trial of buprenorphine and methadone in opiate dependence. Drug and Alcohol Dependence 2001;62(1):97‐104. - PubMed
Schottenfeld 1997 {published and unpublished data}
    1. Schottenfeld RS, Pakes JR, Oliveto A, Ziedonis D, Kosten TR. Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Archives of General Psychiatry 1997;54(8):713‐20. [MEDLINE: ] - PubMed
Schottenfeld 2005 {published data only}
    1. Schottenfeld RS, Chawarski MC, Pakes JR, Pantalon MV, Carroll KM, Kosten TR. Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. American Journal of Psychiatry 2005;162(2):340‐9. - PubMed
Schottenfeld 2008 {published and unpublished data}
    1. Schottenfeld RS, Chawarski MC, Mazlan M. Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double‐blind, placebo‐controlled trial. Lancet 2008;371(9631):2192‐200. - PMC - PubMed
Soyka 2008a {published data only}
    1. Soyka M, Zingg C, Koller G, Kuefner H. Retention rate and substance use in methadone and buprenorphine maintenance therapy and predictors of outcome:results form a randomised study. International Journal of Neuropsychopharmacology 2008;11(5):641‐53. - PubMed
Strain 1994a {published and unpublished data}
    1. Strain E, Stitzer M, Liebson I, Bigelow G. Comparison of buprenorphine and methadone in the treatment of opioid dependence. American Journal of Psychiatry 1994;151(7):1025‐30. [MEDLINE: ] - PubMed
Strain 1994b {published and unpublished data}
    1. Strain E, Stitzer M, Liebson I, Bigelow G. Buprenorphine versus methadone in the treatment of opioid dependent cocaine users. Psychopharmocology 1994;116(4):401‐6. [MEDLINE: ] - PubMed

References to studies excluded from this review

Bickel 1988 {published data only}
    1. Bickel WK, Stitzer ML, Bigelow GE, Liebson IA, Jasinski DR, Johnson RE. A clinical trial of buprenorphine: Comparison with methadone in the detoxification of heroin addicts. Clinical Pharmacology and Therapeutics 1988;43(1):72‐8. [MEDLINE: ] - PubMed
Bond 2004 {published data only}
    1. Bond C, Matheson C, Lawrie T, Cameron I, Robinson A, McNamee P, et al. A randomised comparison of methadone against buprenorphine in the treatment of opioid dependency: a feasibility study. International Journal of Pharmacy Practice 2004;Supplement 2004:R52.
Bouchez 1998 {published data only}
    1. Bouchez J, Beauverie P, Touzeau D. Substitution with buprenorphine in methadone‐ and morphine sulfate‐dependent patients. Preliminary results. European Addiction Research 1998;4(Suppl 1):8‐12. - PubMed
Eder 1998 {published data only}
    1. Eder H, Fischer G, Gombas W, Jagsch R, Stuehlinger G, Kasper S. Comparison of buprenorphine and methadone maintenance in opiate addicts. European Addiction Research 1998;4(Suppl 1):3‐7. - PubMed
Fischer 2006 {published data only}
    1. Fischer G, Ortner R, Rohrmeister K, Jagsch R, Baewert A, Langer M, et al. Methadone versus buprenorphine in pregnant addicts: A double‐blind, double‐dummy comparison study. Addiction 2006;101(2):275‐81. - PubMed
Gerra 2004 {published data only}
    1. Gerra G, Borella F, Zaimovic A, Moi G, Bussandri M, Bibici C, et al. Buprenorphine versus methadone for opioid dependence: Predictor variables for treatment outcome. Drug and Alcohol Dependence 2004;75(1):37‐45. - PubMed
Giacomuzzi 2003 {published data only}
    1. Giacomuzzi SM, Riemer Y, Ertl M, Kemmler G, Rössler H, Hinterhuber H, et al. Buprenorphine versus methadone maintenance treatment in an ambulant setting: A health‐related quality of life assessment. Addiction 2003;98(5):693‐702. - PubMed
Gryczynski 2013 {published data only}
    1. Gryczynski J, Mitchell SG, Jaffe JH, Kelly SM, Myers CP, O'Grady KE, et al. Retention in methadone and buprenorphine treatment among African Americans. Journal of Substance Abuse Treatment 2013;45(3):287‐92. - PMC - PubMed
Harris 2005 {published data only}
    1. Harris AH, Gospodarevskaya E, Ritter A. A randomised trial of the cost effectiveness of buprenorphine as an alternative to methadone maintenance treatment for heroin dependence. Pharmacoeconomics 2005;23(1):77‐91. - PubMed
Johnson 1995b {published data only}
    1. Johnson RE, Eissenberg T, Stitzer ML, Strain EC, Liebson IA, Bigelow GE. Buprenorphine treatment of opioid dependence: Clinical trial of daily versus alternate‐day dosing. Drug and Alcohol Dependence 1995;40(1):27‐35. - PubMed
Jones 2005a {published data only}
    1. Jones HE, Johnson RE, Jasinski DR, Milio L. Randomised controlled study transitioning opioid‐dependent pregnant women from short‐acting morphine to buprenorphine or methadone. Drug and Alcohol Dependence 2005;78(1):33‐8. - PubMed
Jones 2005b {published data only}
    1. Jones HE, Johnson RE, Jasinski DR, O'Grady KE, Chisholm CA, Choo RE, et al. Buprenorphine versus methadone in the treatment of pregnant opioid‐dependent patients: Effects on the neonatal abstinence syndrome. Drug and Alcohol Dependence 2005;79(1):1‐10. - PubMed
Jones 2010a {published data only}
    1. Jones HE, O'Grady KE, Johnson RE, Velez M, Jansson LM. Infant neurobehaviour following prenatal exposure to methadone and buprenorphine: results from the neonatal intensive care unit network neurobehavioural scale. Substance Use and Misuse 2010;45(13):2244‐57. - PubMed
Jones 2010b {published data only}
    1. Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, et al. Neonatal abstinence syndrome after methadone and buprenorphine exposure. New England Journal of Medicine 2010;363(24):2320‐2331. - PMC - PubMed
Kosten 2004 {published data only}
    1. Kosten T, Falcioni J, Oliveto A, Feingold, A. Depression predicts higher rates of heroin use on desipramine with buprenorphine than with methadone. American Journal on Addictions 2004;13(2):191‐201. - PubMed
Lott 2006 {published data only}
    1. Lott DC, Strain EC, Brooner RK, BIgelow GE, Johnson RE. HIV risk behaviors during pharmacologic treatment for opioid dependence: A comparison of levomethadyl acetate [corrected], buprenorphine, and methadone. Journal of Substance Abuse Treatment 2006;31(2):187‐94. - PubMed
Lucas 2010 {published data only}
    1. Lucas GM, Chaudry A, Hsu J, Woodson T, Lau B, Olsen Y, et al. Clinic‐based treatment of opioid‐dependent HIV‐Infected patients versus referral to an opioid treatment program. A randomized trial. Annals of Internal Medicine 2010;152(11):704‐11. - PMC - PubMed
Marsch 2005 {published data only}
    1. Marsch LA, Bickel WK, Badger GJ, Jacobs EA. Buprenorphine treatment for opioid dependence: relative efficacy of daily, twice and thrice weekly dosing. Drug and Alcohol Dependence 2005;77(2):195‐204. - PubMed
McKeganey 2013 {published data only}
    1. McKeganey N, Russell C, Cockayne L. Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine‐naloxone) patients compared. Journal of Substance Abuse Treatment 2013;44(1):97‐102. - PubMed
Meader 2010 {published data only}
    1. Meader N. A comparison of methadone, buprenorphine and alpha2 adrenergic agonists for opioid detoxification: A mixed treatment comparison meta analysis. Drug and Alcohol Dependence 2010;108(1‐2):110‐4. - 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 current opiate and cocaine dependence. Clinical Pharmacology and Therapeutics 2004;75(1):34‐48. - PMC - PubMed
Neumann 2013 {published data only}
    1. Neumann AM, Blondell RD, Jaanimägi MS, 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
O'Connor 1998 {published data only}
    1. O'Connor PG, Oliveto AH, Shi JM, Triffleman EG, Carroll KM, Kosten TR, et al. A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic. American Journal of Medicine 1998;105(2):100‐5. - PubMed
Oliveto 1994 {published data only}
    1. Oliveto A, Kosten T, Schottenfeld R, Ziedonis D, Falcioni J. Cocaine use in buprenorphine vs methadone maintained patients. American Journal on Addictions 1994;3(1):43‐8.
Pinto 2008 {published data only}
    1. Pinto H, Rumball D, Maskrey V, Holland R. A pilot study for a randomized controlled and patient preference trial of buprenorphine versus methadone maintenance treatment in the management of opiate dependent patients. Journal of Substance Use 2008;13(2):73‐82.
Resnick 1992 {published data only}
    1. Resnick RB, Galanter M, Pycha C, Cohen A, Grandison P, Flood N. Buprenorphine: An alternative to methadone for heroin dependence treatment.. Psychopharmacology Bulletin 1992;28(1):109‐13. - PubMed
Sacerdote 2008 {published data only}
    1. Sacerdote P, Franchi S, Gerra G, Leccese V, Panerai AE, Somaini L. Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function. Brain, Behavior, and Immunity 2008;22(4):606‐13. - PubMed
Schottenfeld 1998 {published data only}
    1. Schottenfeld R, Pakes J, Kosten T. Prognostic factors in buprenorphine‐ versus methadone‐maintained patients. Journal of Nervous and Mental Disease 1998;186(1):35‐43. [MEDLINE: ] - PubMed
Sigmon 2004 {published data only}
    1. Sigmon S, Wong C, Chausmer A, Liebson I, Bigelow G. Evaluation of an injection depot formulation of buprenorphine: placebo comparison. Addiction 2004;99(11):1439‐49. - PubMed
Soyka 2008b {published data only}
    1. Soyka M, Lieb M, Kagerer S, Zingg C, Koller G, Lehnert P, et al. Cognitive functioning during methadone and buprenorphine treatment: Results of a randomized clinical trial. Journal of Clinical Psychopharmacology 2008;28(6):699‐703. - PubMed
Stine 1994 {published data only}
    1. Stine SM, Kosten TR. Reduction of opiate withdrawal‐like symptoms by cocaine abuse during methadone and buprenorphine maintenance. Am J Drug Alcohol Abuse 1994;20(4):445‐58. [MEDLINE: ] - 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. [MEDLINE: ] - PubMed
Uehlinger 1998 {published and unpublished data}
    1. Uehlinger C, Déglon J, Livoti S, Petitjean S, Waldvogel D, Ladewig D. Comparison of buprenorphine and methadone in the treatment of opioid dependence. Eur Addict Res 1998;4 Suppl 1:13‐8. - PubMed
Warden 2012 {published data only}
    1. Warden D, Subramaniam GA, Carmody T, Woody GE, Minhajuddin A, Poole SA, et al. Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth. Addictive Behaviors 2012;37(9):1046‐53. - PMC - PubMed
Weiss 2011 {published data only}
    1. Weiss RD, Sharpe Potter JS, Fiellin DA, Byrne M, Connery HS, Dickinson W, et al. Adjunctive counseling during brief and extended buprenorphine‐naloxone treatment for prescription opioid dependence: A 2‐phase randomized controlled trial. Archives of General Psychiatry 2011;68(12):1238‐46. - PMC - PubMed
Woody 2008 {published data only}
    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 awaiting assessment

Ahmadi 2002b {published data only}
    1. Ahmadi, J. Buprenorphine maintenance treatment of heroin dependence: the first experience from Iran. Journal of Substance Abuse Treatment 2002;22:157‐9. - PubMed
Cropsey 2011 {published data only}
    1. Cropsey KL, Lane PS, Hale GJ, Jackson DO, Clark CB, Ingersoll KS, et al. Results of a pilot randomized controlled trial of buprenorphine for opioid dependent women in the criminal justice system. Drug and Alcohol Dependence 2011;119(3):172‐8. - PMC - PubMed

Additional references

Barnett 2001
    1. Barnett PG, Rodgers JH, Bloch D. A meta‐analysis comparing buprenorphine to methadone for treatment of opiate dependence. Addiction 2001;96(5):683‐90. - PubMed
Clark 2002
    1. Clark NC, Lintzeris N, Gijsbers A, Whelan G, Dunlop A, Ritter A, Ling WW. LAAM maintenance vs methadone maintenance for heroin dependence. Cochrane Database of Systematic Reviews 2002, Issue 2. [DOI: 10.1002/14651858.CD002210] - DOI - PubMed
Clausen 2008
    1. Clausen T, Anchersen K, Waal H. Mortality prior to, during and after opioid maintenance treatment (OMT): A national prospective cross‐registry study. Drug and Alcohol Dependence 2008;94(1‐3):151‐7. - PubMed
Connock 2007
    1. Connock M, Juarez‐Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al. Methadone and buprenorphine for the management of opioid dependence; a systematic review and economic evaluation. Health Technology Assessment 2007;11(9):1‐190. - PubMed
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. - PubMed
Degenhardt 2011
    1. Degenhardt L, Bucello C, Mathers B, Briegleb C, Ali H, Hickman M, et al. Mortality among regular or dependent users of heroin and other opioids: A systematic review and meta‐analysis of cohort studies. Addiction 2011;106(1):32‐51. - PubMed
Degenhardt 2012
    1. Degenhardt L, Hall W. Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet 2012;379(9810):55‐70. - PubMed
Dole 1965
    1. Dole VP, Nyswander M. A medical treatment for diacetylmorphine (heroin) addiction: a clinical trial with methadone hydrochloride. JAMA 1965;193:646‐50. - PubMed
Drummer 1992
    1. Drummer OH, Opeskin K, Syrjanen M, Cordner SM. Methadone toxicity causing death in ten subjects starting on a methadone maintenance program.. American Journal of Forensic Medicine and Pathology 1992;13(4):346–50. - PubMed
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. [DOI: 10.1002/14651858.CD002208] - DOI - PubMed
Fudala 1990
    1. Fudala PJ, Jaffe JH, Dax EM, Johnson RE. Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate‐day administration and abrupt withdrawal. Clinical Pharmacology and Therapeutics 1990;47(4):525‐34. - PubMed
Gibson 2008
    1. Gibson A, Degenhardt L, Mattick RP, Ali R, White J, O'Brien S. Exposure to opioid maintenance treatment reduces long‐term mortality. Addiction 2008;103(3):462‐8. - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Jasinski 1978
    1. Jasinski D, Pevnick J, Griffith J. Human pharmacology and abuse potential of the analgesic buprenorphine. Archives of General Psychiatry 1978;35(4):501‐6. - PubMed
Lind 2005
    1. Lind B, Chen S, Weatherburn D, Mattick R. The effectiveness of methadone maintenance treatment in controlling crime. An Australian aggregate‐level analysis. Journal of Criminology 2005;45(2):201‐11.
Ling 2003
    1. Ling W, Wesson DR. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug and Alcohol Dependence 2003;70(2 Suppl):S49‐57. - PubMed
Mathers 2008
    1. Mathers BM, Degenhardt L, Phillips B, Wiessing L, Hickman M, Strathdee SA, et al. Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review. Lancet 2008;372(9651):1733‐45. - PubMed
Mattick 1998
    1. Mattick RP, Oliphant D, Ward J, Hall W. The effectiveness of other opioid replacement therapies: LAAM, heroin, buprenorphine, naltrexone and injectable maintenance. Methadone maintenance and other opioid replacement therapies. Amsterdam: Harwood Academic Publishers, 1998:123‐60. [DOI: 10.1002/14651858] - 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. [DOI: 10.1002/14651858.CD002209.pub2] - DOI - PMC - PubMed
Minozzi 2013
    1. Minozzi S, Amato L, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate dependent pregnant women. Cochrane Database of Systematic Reviews 2013, Issue 12. [DOI: 10.1002/14651858.CD006318.pub3] - DOI - PubMed
Mitchell 2004
    1. Mitchell TB, White JM, Somogyi AA, Bochner F. Slow‐release oral morphine versus methadone: a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Addiction 2004;99(8):940‐5. - PubMed
Nelson 2011
    1. Nelson PK, Mathers BM, Cowie B, Hagan H, Jarlais D, Horyniak D, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 2011;378(9791):571‐83. - PMC - PubMed
Perneger 1998
    1. Perneger TV, Giner F, Rio M, Mino A. Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments. BMJ 1998;317(7150):13‐8. - PMC - PubMed
Soyka 2011
    1. Soyka M, Träder A, Klotsche J, Backmund M, Bühringer G, Rehm J, et al. Six‐year mortality rates of patients in methadone and buprenorphine maintenance therapy: results form a nationally representative cohort study. Journal of Clinical Psychopharmacology 2011;31(5):678‐80. - PubMed
UNODC 2012
    1. UNODC. World Drug Report 2012. www.unodc.org/unodc/en/data‐and‐analysis/WDR‐2012.html (accessed 6 January 2014) 2012; Vol. Sales No E.12.XI.1.
West 2000
    1. West S, O'Neal K, Graham C. A meta‐analysis comparing the effectiveness of buprenorphine and methadone. Journal of Substance Abuse 2000;12(4):405‐14. - PubMed
White 2007
    1. White JM, Lopatko OV. Opioid maintenance: a comparative review of pharmacological strategies. Expert Opinion on Pharmacotherapy 2007;8(1):1‐11. - PubMed

References to other published versions of this review

Mattick 2008
    1. Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD002207.pub3] - DOI - PubMed

Publication types

MeSH terms