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Meta-Analysis
. 2013 Jun 5;2013(6):CD009879.
doi: 10.1002/14651858.CD009879.pub2.

Slow-release oral morphine as maintenance therapy for opioid dependence

Marica Ferri  1 , Silvia Minozzi, Alessandra Bo, Laura Amato
Affiliations
Meta-Analysis

Slow-release oral morphine as maintenance therapy for opioid dependence

Marica Ferri et al. Cochrane Database Syst Rev. .

Abstract

Background: Opioid substitution treatments are effective in retaining people in treatment and suppressing heroin use. An open question remains whether slow-release oral morphine (SROM) could represent a possible alternative for opioid-dependent people who respond poorly to other available maintenance treatments.

Objectives: To evaluate the efficacy of SROM as an alternative maintenance pharmacotherapy for the treatment of opioid dependence.

Search methods: We searched Cochrane Drugs and Alcohol Group's Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 3, 2013), MEDLINE (January 1966 to April 2013), EMBASE (January 1980 to April 2013) and reference lists of articles.

Selection criteria: Randomised controlled trials (RCTs) and quasi-randomised trials assessing efficacy of SROM compared with other maintenance treatment or no treatment.

Data collection and analysis: Two review authors independently selected articles for inclusion, extracted data and assessed risk of bias of included studies.

Main results: Three studies with 195 participants were included in the review. Two were cross-over trials and one was a parallel group RCT. The retention in treatment appeared superior to 80% in all the three studies (without significant difference with controls). Nevertheless, it has to be underlined that the studies had different durations. One lasted six months, and the other two lasted six and seven weeks. The use of opioids during SROM provision varied from lower to non-statistically or clinically different from comparison interventions, whereas there were no differences as far as the use of other substances was concerned.SROM seemed to be equal to comparison interventions for severity of dependence, or mental health/social functioning, but there was a trend for less severe opiate withdrawal symptoms in comparison with methadone (withdrawal score 2.2 vs. 4.8, P value = 0.06). Morphine was generally well tolerated and was preferred by a proportion of participants (seven of nine people in one study). Morphine appeared to reduce cravings, depressive symptoms (measured using the Beck Depression Inventory; P value < 0.001), physical complaints (measured using the Beschwerde-Liste (BL); P value < 0.001) and anxiety symptoms (P value = 0.008). Quality of life in people treated with SROM resulted in no significant difference or a worst outcome than in those taking methadone and buprenorphine. Other social functioning measures, such as finances, family and overall satisfaction, scored better in people maintained with the comparison substances than in those maintained with SROM. In particular, people taking methadone showed more favourable values for leisure time (5.4 vs. 3.7, P value < 0.001), housing (6.1 vs. 4.7, P value < 0.023), partnerships (5.7 vs. 4.2, P value = 0.034), friend and acquaintances (5.6 vs. 4.4, P value = 0.003), mental health (5.0 vs. 3.4, P value = 0.002) and self esteem (8.2 vs. 5.7, P value = 0.002) compared to people taking SROM; while people taking buprenorphine obtained better scores for physical health.Medical adverse events were consistently higher in people in SROM than in the comparison groups. None of the studies included people with a documented poor response to other maintenance treatment.

Authors' conclusions: The present review did not identify sufficient evidence to assess the effectiveness of SROM for opioid maintenance because only three studies meeting our inclusion criteria have been identified. Two studies suggested a possible reduction of opioid use in people taking SROM. In another study, the use of SROM was associated with fewer depressive symptoms. Retention in treatment was not significantly different among compared interventions while the adverse effects were more frequent with the people given SROM.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Clark 2002 {published data only}
    1. Clark N, Khoo K, Lintzeris N, Ritter A, Whelan G. A randomised trial of once‐daily slow‐release oral morphine versus methadone for heroin dependence. Drug and Alcohol Dependence 2002;66 Suppl 1:S33.
Eder 2005 {published data only}
    1. Eder H, Jagsch R, Kraigher D, Primorac A, Ebner N, Fischer G. Comparative study of the effectiveness of slow‐release morphine and methadone for opioid maintenance therapy. Addiction 2005;100(8):1101‐9. - PubMed
    1. Eder H, Kraigher D, Peternel R, Ortner R, Schindler S, Kasper S, et al. Methadone versus slow‐relapse morphine maintenance for the treatment of opioid dependence. Drug and Alcohol Dependence 2001;63 Suppl 1:S42.
    1. Winklbaur B, Jagsch R, Ebner N, Thau K, Fischer G. Quality of life in patients receiving opioid maintenance therapy. A comparative study of slow‐release morphine versus methadone treatment. European Addiction Research 2008;14(2):99‐105. - PubMed
Giacomuzzi 2006 {published data only}
    1. Giacomuzzi S, Kemmler G, Ertl M, Riemer Y. Opioid addicts at admission vs. slow‐release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants . Substance Use and Misuse 2006;41(2):223‐44. - PubMed

References to studies excluded from this review

Bond 2012 {published data only}
    1. Bond AJ, Reed KDF, Beavan P, Strang J. After the randomised injectable opiate treatment trial: post‐trial investigation of slow‐release oral morphine as an alternative opiate maintenance medication. Drug and Alcohol Review 2012;31(4):492‐8. - PubMed
Madlung‐Kratzer 2009 {published data only}
    1. Madlung‐Kratzer E, Spitzer B, Brosch R, Dunkel D, Haring C. A double‐blind, randomised, parallel group study to compare the efficacy, safety and tolerability of slow‐release oral morphine versus methadone in opioid‐dependent in‐patients willing to undergo detoxification. Addiction 2009;104(9):1549‐57. - PMC - PubMed
Mitchell 2003 {published data only}
    1. Mitchell TB, White JM, Somogyi AA, Bochner F. Comparative pharmacodynamics and pharmacokinetics of methadone and slow‐release oral morphine for maintenance treatment of opioid dependence. Drug and Alcohol Dependence 2003;72(1):85‐94. - PubMed
Mitchell 2004 {published data only}
    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
Mitchell 2006 {published data only}
    1. Mitchell TB, White JM, Somogyi AA, Bochner F. Switching between methadone and morphine for maintenance treatment of opioid dependence: impact on pain sensitivity and mood status. American Journal on Addictions 2006;15:311‐5. - PubMed
Moldovanyi 1996 {published data only}
    1. Moldovanyi A, Ladewig D, Affentranger P, Natsch C, Stohler R. Morphine maintenance treatment of opioid‐dependent out‐patients. European Addiction Research 1996;2:208‐12.

References to studies awaiting assessment

Fischer 1996 {published data only}
    1. Fischer G, Presslich O, Diamant K, Schneider C, Pezawas L, Kasper S. Oral morphine‐sulfate in the treatment of opiate dependent patients. Alcoholism 1996;32:35‐43.
Sherman 1996 {published data only}
    1. Sherman JP. Managing heroin addiction with a long‐acting morphine product. The Medical Journal of Australia 1996;165:239. - PubMed

References to ongoing studies

NCT01079117‐SROM {published data only}
    1. Morphine Slow‐release Capsules in Substitution Therapy. Ongoing study October 2006.

Additional references

Amato 2011
    1. Amato L, Minozzi S, Davoli M, Vecchi S. Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Cochrane Database of Systematic Reviews 2011, Issue 10. [DOI: 10.1002/14651858.CD004147] - DOI - PubMed
Beer 2010
    1. Beer B, Rabl W, Libiseller K, Giacomuzzi S, Riemer Y, Pavlic M. Impact of slow‐release oral morphine on drug abusing habits in Austria [Der Einfluss von retardiertem Morphin auf die Drogensituation in Osterreich]. Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation: Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater 2010;24(2):108‐17. [PUBMED: 20605006] - PubMed
Clark 2008
    1. Clark NC, 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 2008, Issue 2. [DOI: 10.1002/14651858.CD002210] - DOI - PubMed
Davoli 2007
    1. Davoli M, Bargagli AM, Perucci CA, Schifano P, Belleudi V, Hickman M, et al. Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi‐site prospective cohort study. Addiction (Abingdon, England) 2007;102:1954‐9. - PubMed
EMCDDA 2011
    1. European Monitoring Centre for Drugs and Drug Addiction. Annual Report. The State of Drugs Problem in Europe. Lisbon: European Monitoring Centre for Drugs and Drug Addiction, 2011.
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
Ferri 2007
    1. Ferri M, Bargagli AM, Faggiano F, Belleudi V, Salamina G, Vigna‐Taglianti F, et al. Mortality of drug users attending public treatment centres in Italy 1998‐2001: a cohort study [Mortalita in una coorte di tossicodipendenti da eroina arruolati presso i Ser.T in Italia, 1998‐2001]. Epidemiologia e Prevenzione 2007;31:276‐82. - PubMed
Ferri 2011
    1. Ferri M, Davoli M, Perucci CA. Heroin maintenance for chronic heroin‐dependent individuals. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD003410] - DOI - PMC - PubMed
GRADE Working Group 2004
    1. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490. - PMC - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck‐Ytter Y, Schünemann HJ. What is 'quality of evidence' and why is it important to clinicians?. BMJ 2008;336:995‐8. - PMC - PubMed
Guyatt 2010
    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 2010;64:383‐94. - 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.
Jegu 2011
    1. Jegu J, Gallini A, Soler P, Montastruc J L, Lapeyre‐Mestre M. Slow‐release oral morphine for opioid maintenance treatment: a systematic review. British Journal of Clinical Pharmacology 2011;71(6):832‐43. - PMC - PubMed
Kastelic 2008
    1. Kastelic A, Dubajic G, Strbad E. Slow‐release oral morphine for maintenance treatment of opioid addicts intolerant to methadone or with inadequate withdrawal suppression. Addiction (Abingdon, England) 2008;103:1837‐46. - PubMed
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] - DOI - PubMed
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] - DOI - PMC - PubMed
Schünemann 2006
    1. Schünemann HJ, Jaeschke R, Cook DJ, Bria WF, El‐Solh AA, Ernst A, et al. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. American Journal of Respiratory and Critical Care Medicine 2006;174:605‐14. - PubMed
Soyka 2011
    1. Soyka M, Kranzler HR, Brink W, Krystal J, Moller HJ, Kasper S. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of substance use and related disorders. Part 2: opioid dependence. The World Journal of Biological Psychiatry: the Official Journal of the World Federation of Societies of Biological Psychiatry 2011;12(3):160‐87. [PUBMED: 21486104] - PubMed
UNODC 2011
    1. United Nations Office on Drugs and Crime. World Drug Report. United Nations Office on Drugs and Crime, No. E.11.XI.10, 2011.
van den Brink 2012
    1. Brink. Evidence‐based pharmacological treatment of substance use disorders and pathological gambling. Current drug abuse reviews 2012;5(1):3‐31. [PUBMED: 22126708] - PubMed
WHO 2009
    1. World Health Organization. Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. Geneva: World Health Organization, 2009.

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