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Meta-Analysis
. 2017 May 29;5(5):CD002021.
doi: 10.1002/14651858.CD002021.pub4.

Opioid antagonists with minimal sedation for opioid withdrawal

Linda Gowing  1 , Robert Ali  1 , Jason M White  2
Affiliations
Meta-Analysis

Opioid antagonists with minimal sedation for opioid withdrawal

Linda Gowing et al. Cochrane Database Syst Rev. .

Abstract

Background: Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment.

Objectives: To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications.

Search methods: We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies.

Selection criteria: We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants.

Data collection and analysis: We used standard methodological procedures expected by Cochrane.

Main results: Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha2-adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient without indicating the level of care provided.The included studies were heterogeneous in terms of the type of opioid antagonist treatment regimen, the comparator, the outcome measures assessed, and the means of assessing outcomes. As a result, the validity of any estimates of overall effect is doubtful, therefore we did not calculate pooled results for any of the analyses.The quality of the evidence for treatment with an opioid antagonist-adrenergic agonist combination versus an alpha2-adrenergic agonist is very low. Two studies reported data on peak withdrawal severity, and four studies reported data on the average severity over the period of withdrawal. Peak withdrawal induced by opioid antagonists in combination with an adrenergic agonist appears to be more severe than withdrawal managed with clonidine or lofexidine alone, but the average severity over the withdrawal period is less. In some situations antagonist-induced withdrawal may be associated with significantly higher rates of treatment completion compared to withdrawal managed with adrenergic agonists. However, this result was not consistent across studies, and the extent of any benefit is highly uncertain.We could not extract any data on the occurrence of adverse events, but two studies reported delirium or confusion following the first dose of naltrexone. Delirium may be more likely with higher initial doses and with naltrexone rather than naloxone (which has a shorter half-life), but we could not confirm this from the available evidence.Insufficient data were available to make any conclusions on the best duration of treatment.

Authors' conclusions: Using opioid antagonists plus alpha2-adrenergic agonists is a feasible approach for managing opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.Using opioid antagonists to induce and accelerate opioid withdrawal is not currently an active area of research or clinical practice, and the research community should give greater priority to investigating approaches, such as those based on buprenorphine, that facilitate the transition to sustained-release preparations of naltrexone.

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Conflict of interest statement

Linda Gowing: none known.

Robert Ali: none known.

Jason White: none known.

Figures

1
1
Flow diagram of literature search
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Antagonist‐adrenergic combination versus adrenergic agonist, Outcome 1 Peak withdrawal severity.
1.2
1.2. Analysis
Comparison 1 Antagonist‐adrenergic combination versus adrenergic agonist, Outcome 2 Overall withdrawal severity.
1.3
1.3. Analysis
Comparison 1 Antagonist‐adrenergic combination versus adrenergic agonist, Outcome 3 Completion rate.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Arnold‐Reed 2005 {published data only}
    1. Arnold‐Reed DE, Hulse GK. A comparison of rapid (opioid) detoxification with clonidine‐assisted detoxification for heroin‐dependent persons. Journal of Opioid Management 2005;1(1):17‐23. - PubMed
Bearn 2001 {published data only}
    1. Bearn J, Bennett J, Martin T, Gossop M, Strang J. The impact of naloxone/lofexidine combination treatment on the opiate withdrawal syndrome. Addiction Biology 2001;6(2):147‐56. - PubMed
Beswick 2003 {published data only}
    1. Beswick T, Best D, Bearn J, Gossop M, Rees S, Strang J. The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double‐blind randomized and placebo‐controlled trial. American Journal on Addictions 2003;12(4):295‐305. - PubMed
    1. Beswick T, Best D, Rees S, Bearn J, Gossop M, Strang J. Major disruptions of sleep during treatment of the opiate withdrawal syndrome: differences between methadone and lofexidine detoxification treatments. Addiction Biology 2003;8(1):49‐57. - PubMed
Buntwal 2000 {published data only}
    1. Buntwal N, Bearn J, Gossop M, Strang J. Naltrexone and lofexidine combination treatment compared with conventional lofexidine treatment for in‐patient opiate detoxification. Drug and Alcohol Dependence 2000;59(2):183‐8. - PubMed
Gerra 1995 {published data only}
    1. Gerra G, Marcato A, Caccavari R, Fontanesi B, Delsignore R, Fertonani G, et al. Clonidine and opiate receptor antagonists in the treatment of heroin addiction. Journal of Substance Abuse Treatment 1995;12(1):35‐41. - PubMed
Gerra 2000 {published data only}
    1. Gerra G, Zaimovic A, Rustichelli P, Fontanesi B, Zambelli U, Timpano M, et al. Rapid opiate detoxification in outpatient treatment: Relationship with naltrexone compliance. Journal of Substance Abuse Treatment 2000;18(1):185‐91. - PubMed
McCambridge 2007 {published data only}
    1. McCambridge J, Gossop M, Beswick T, Best D, Bearn J, Rees S, et al. In‐patient detoxification procedures, treatment retention, and post‐treatment opiate use: comparison of lofexidine+naloxone, lofexidine+placebo, and methadone. Drug and Alcohol Dependence 2007;88(1):91‐5. - PubMed
O'Connor 1995 {published data only}
    1. O'Connor PG, Waugh ME, Carroll KM, Rounsaville BJ, Diakogiannis IA, Schottenfeld RS. Primary care‐based ambulatory opioid detoxification: the results of a clinical trial. Journal of General Internal Medicine 1995;10(5):255‐60. - PubMed
    1. O'Connor PG, Waugh ME, Schottenfeld RS, Diakogiannis IA, Diakogiannis IA, Rounsaville BJ. Ambulatory opiate detoxification and primary care: a role for the primary care physician. Journal of General Internal Medicine 1992;7(Sept/Oct):532‐4. - PubMed
O'Connor 1997 {published data only}
    1. O'Connor PG, Carroll KM, Shi JM, Schottenfeld RS, Kosten TR, Rounsaville BJ. Three methods of opioid detoxification in a primary care setting. A randomized trial. Annals of Internal Medicine 1‐10‐1997;127(7):526‐30. - PubMed
    1. Shi JM, O'Connor PG, Constantino JA, Carroll KM, Schottenfeld RS, Rounsaville BJ. Three methods of ambulatory opiate detoxification: preliminary results of a randomized clinical trial. NIDA Research Monograph 1993;132:309.
Umbricht 1999 {published data only}
    1. Umbricht A, Montoya ID, Hoover DR, Demuth KL, Chiang CT, Preston KL. Naltrexone shortened opioid detoxification with buprenorphine. Drug and Alcohol Dependence 1‐10‐1999;56(3):181‐90. - PubMed

References to studies excluded from this review

Armstrong 2003 {published data only}
    1. Armstrong J, Little M, Murray L. Emergency department presentations of naltrexone‐accelerated detoxification. Academic Emergency Medicine 2003;10(8):860‐6. - PubMed
Azatian 1994 {published data only}
    1. Azatian A, Papiasvilli A, Joseph H. A study of the use of clonidine and naltrexone in the treatment of opioid dependence in the former USSR. Journal of Addictive Diseases 1994;13(1):35‐52. - PubMed
Bartter 1996 {published data only}
    1. Bartter T, Gooberman LL. Rapid opiate detoxification. American Journal of Drug Alcohol Abuse 1996;22(4):489‐95. - PubMed
Beaini 2000 {published data only}
    1. Beaini AY, Johnson TS, Langstaff P, Carr MP, Crossfield JN, Sweeney RC. A compressed opiate detoxification regime with naltrexone maintenance: patient tolerance, risk assessment and abstinence rates. Addiction Biology 2000;5(4):451‐62. - PubMed
Bell 1999 {published data only}
    1. Bell JR, Young MR, Masterman SC, Morris A, Mattick RP, Bammer G. A pilot study of naltrexone‐accelerated detoxification in opioid dependence. Medical Journal of Australia 1999;171(1):26‐30. - PubMed
Brewer 1988 {published data only}
    1. Brewer C. Naloxone in heroin withdrawal. British Journal of Psychiatry 1988;153:120. - PubMed
    1. Brewer C, Rezae H, Bailey C. Opioid withdrawal and naltrexone induction in 48‐72 hours with minimal drop‐out, using a modification of the naltrexone‐clonidine technique. British Journal of Psychiatry 1988;153:340‐3. - PubMed
Camarasa 2007 {published data only}
    1. Camarasa X, Khazaal Y, Besson J, Zullino DF. Naltrexone‐assisted rapid methadone discontinuation: a pilot study. European Addiction Research 2007;13(1):20‐4. - PubMed
Carreno 2002 {published data only}
    1. Carreno JE, Bobes J, Brewer C, Alvarez CE, San Narciso GI, Bascaran MT, et al. 24‐Hour opiate detoxification and antagonist induction at home ‐ The 'Asturian method': a report on 1368 procedures. Addiction Biology 2002;7(2):243‐50. - PubMed
Charney 1986 {published data only}
    1. Charney DS, Heninger GR, Kleber HD. The combined use of clonidine and naltrexone as a rapid, safe and effective treatment of abrupt withdrawal from methadone. American Journal of Psychiatry 1986;143(7):831‐7. - PubMed
    1. Charney DS, Riordan CE, Kleber HD, Murburg M, Braverman P, Sternberg DE, et al. Clonidine and naltrexone: a safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy. Archives of General Psychiatry 1982;39(11):1327‐32. - PubMed
Chen 2004 {published data only}
    1. Chen TJH, Blum K, Payte JT, Schoolfield J, Hopper D, Stanford M, et al. Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN‐10, amino‐acid precursors and enkephalinase inhibition therapy. Medical Hypotheses 2004;63(3):538‐48. - PubMed
Dakwar 2015 {published data only}
    1. Dakwar E, Kleber HD. Naltrexone‐facilitated buprenorphine discontinuation: a feasibility trial. Journal of Substance Abuse Treatment 2015;53:60‐3. - PubMed
De Jong 2005 {published data only}
    1. Jong CAJ, Laheij RJF, Krabbe PFM. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial. Addiction 2005;100(2):206‐15. - PubMed
    1. Dijkstra BA, Jong CA, Krabbe PF, Staak CP. Prediction of abstinence in opioid‐dependent patients. Journal of Addiction Medicine 2008;2(4):194‐201. - PubMed
    1. Dijkstra BAG, Krabbe PFM, Jong CAJ, Staak CPF. Prediction of withdrawal symptoms during opioid detoxification. Journal of Opioid Management 2008;4(5):311‐9. - PubMed
Dijkstra 2010 {published data only}
    1. Dijkstra BAG, Jong CAJ, Wensing M, Krabbe PFM, Staak CPF. Opioid detoxification: from controlled clinical trial to clinical practice. American Journal on Addictions 2010;19(3):283‐90. - PubMed
Frownfelter 2001 {published data only}
    1. Frownfelter J, Hopper JA. Rapid opioid detoxification using buprenorphine and naltrexone. Drug and Alcohol Dependence 2001;63(Suppl 1):S50.
Gerra 2001 {published data only}
    1. Gerra G, Zaimovic A, Giusti F, Gennaro C, Zambelli U, Gardini S, et al. Lofexidine versus clonidine in rapid opiate detoxification. Journal of Substance Abuse Treatment 2001;21(1):11‐7. - PubMed
Gerra 2006 {published data only}
    1. Gerra G, Fantoma A, Zaimovic A. Naltrexone and buprenorphine combination in the treatment of opioid dependence. Journal of Psychopharmacology 2006;20(6):806‐14. - PubMed
Glasgow 2001 {published data only}
    1. Glasgow NJ, Taylor J, Bell JR, Young MR, Bammer G. Accelerated withdrawal from methadone maintenance therapy using naltrexone and minimal sedation: a case‐series analysis. Drug and Alcohol Review 2001;20(2):213‐21.
Golden 2004 {published data only}
    1. Golden SA, Sakhrani DL. Unexpected delirium during Rapid Opioid Detoxification (ROD). Journal of Addictive Diseases 2004;23(1):65‐75. - PubMed
Kleber 1987 {published data only}
    1. Kleber HD, Topazian M, Gaspari J, Riordan CE, Kosten T. Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. American Journal of Drug and Alcohol Abuse 1987;13(1‐2):1‐17. - PubMed
Kurland 1976 {published data only}
    1. Kurland AA, McCabe L. Rapid detoxification of the narcotic addict with naloxone hydrochloride. A preliminary report. Journal of Clinical Pharmacology 1976;16(1):66‐74. - PubMed
London 1999 {published data only}
    1. London M, Paul E, Gkolia I. Ultra‐rapid opiate detoxification in hospital. Psychiatric Bulletin 1999;23(9):544‐6.
Mannelli 2003 {published data only}
    1. Mannelli P, Gottheil E, Buonanno A, Risio S. Use of very low‐dose naltrexone during opiate detoxification. Journal of Addictive Diseases 2003;22(2):63‐70. - PubMed
Mannelli 2009 {published data only}
    1. Mannelli P, Patkar AA, Peindl K, Gorelick DA, Wu L‐T, Gottheil E. Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial. Addiction Biology 2009;14(2):204‐13. - PMC - PubMed
    1. Mannelli P, Patkar AA, Peindl K, Gottheil E, Wu L‐T, Gorelick DA. Early outcomes following low dose naltrexone enhancement of opioid detoxification. American Journal on Addictions 2009;18(2):109‐16. - PMC - PubMed
    1. Mannelli P, Peindl K, Patkar AA, Wu L‐T, Pae C‐U, Gorelick DA. Reduced cannabis use after low‐dose naltrexone addition to opioid detoxification. Journal of Clinical Psychopharmacology 2010;30(4):476‐8. - PMC - PubMed
    1. Mannelli P, Peindl K, Patkar AA, Wu L‐T, Tharwani HM, Gorelick DA. Problem drinking and low‐dose naltrexone‐assisted opioid detoxification. Journal of Studies on Alcohol and Drugs 2011;72(3):507‐13. - PMC - PubMed
    1. Mannelli P, Peindl K, Wu L‐T, Patkar AA, Gorelick DA. The combination very low‐dose naltrexone‐clonidine in the management of opioid withdrawal. American Journal of Drug and Alcohol Abuse 2012;38(3):200‐5. - PMC - PubMed
Mannelli 2014 {published data only}
    1. Mannelli P, Wu LT, Peindl KS, Swartz MS, Woody GE. Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial. Drug and Alcohol Dependence 2014;138(1):83‐8. - PMC - PubMed
Masini 1981 {published data only}
    1. Masini E, Blandina P, Mannaioni PF, Luciani G. Clonidine and naloxone for rapid opiate detoxication: comparison between treatments. Clinical Toxicology 1981;18(9):1021‐6. - PubMed
Mogali 2015 {published data only}
    1. Mogali S, Khan NA, Drill ES, Pavlicova M, Sullivan MA, Nunes E, et al. Baseline characteristics of patients predicting suitability for rapid naltrexone induction. American Journal on Addictions 2015;24(3):258‐64. - PMC - PubMed
Montazeri 2002 {published data only}
    1. Montazeri K, Farahnakian M, Saghaei M. The effect of acupuncture on the acute withdrawal symptoms from rapid opiate detoxification. Acta Anaesthesiologica Sinica 2002;40(4):173‐7. - PubMed
Montoya 1994 {published data only}
    1. Montoya ID, Mann DJ, Ellison PA, Lange WR, Preston KL. Inpatient medically supervised opioid withdrawal, with buprenorphine alone and in combination with naltrexone. Clinical Pharmacology and Therapeutics 1994;55(2):131.
Pozzi 2000 {published data only}
    1. Conte G, Scetta G, Moscianese K, Pozzi G. Trazodone versus clonidine in rapid detoxification from opiates. Ninth European College of Neuropsychopharmacology Congress, 1996 Sep 21‐25; Amsterdam. European College of Neuropsychopharmacology, 1996.
    1. Pozzi G, Conte G, Risio S. Combined use of trazodone‐naltrexone versus clonidine‐naltrexone in rapid withdrawal from methadone treatment. A comparative inpatient study. Drug and Alcohol Dependence 2000;59(3):287‐94. - PubMed
Resnick 1977 {published data only}
    1. Resnick RB, Kestenbaum RS, Washton A, Poole D. Naloxone‐precipitated withdrawal: a method for rapid induction onto naltrexone. Clinical Pharmacology & Therapeutics 1977;21(4):409‐13. - PubMed
Rezaiyan 2014 {published data only}
    1. Rezaiyan MK, Moghadam HK, Khosrojerdi H, Afshari R. Very low‐dose naltrexone versus placebo in alleviating withdrawal manifestation. Clinical Toxicology 2014;52(4):368.
Riordan 1980 {published data only}
    1. Riordan CE, Kleber HD. Rapid opiate detoxification with clonidine and naloxone. Lancet 1980;5(8177):1079‐80. - PubMed
Saunders 2002 {published data only}
    1. Dean AJ, Saunders JB, Jones RT, Young RM, Connor JP, Lawford BR. Findings from a randomized controlled trial in subjects with opioid dependence. Journal of Psychiatry and Neuroscience 2006;31(1):38‐45. - PMC - PubMed
    1. Saunders JB, Jones R, Dean A, Connor J, Young R, Keen L, et al. Comparison of rapid opiate detoxification and naltrexone with methadone maintenance in the treatment of opiate dependence: a randomized controlled trial. Drug and Alcohol Dependence 8‐6‐2002;66(Suppl 1):S156.
Senft 1991 {published data only}
    1. Senft RA. Experience with clonidine‐naltrexone for rapid opiate detoxification. Journal of Substance Abuse Treatment 1991;8(4):257‐9. [MEDLINE: ] - PubMed
Silverstone 1992 {published data only}
    1. Silverstone PH, Attenburrow MJ, Robson P. The calcium channel antagonist nifedipine causes confusion when used to treat opiate withdrawal in morphine‐dependent patients. International Clinical Psychopharmacology 1992;7(2):87‐90. - PubMed
Sullivan 2015 {published data only}
    1. Sullivan MA, Bisaga A, Carpenter K, Mariani JJ, Mishlen K, Nunes EV. Long‐acting injectable naltrexone induction: a randomized trial of outpatient opioid detoxification with naltrexone vs buprenorphine. Drug and Alcohol Dependence 2015;146:e112. - PMC - PubMed
Vining 1988 {published data only}
    1. Vining E, Kosten TR, Kleber HD. Clinical utility of rapid clonidine naltrexone detoxification for opioid abusers. British Journal of Addiction 1988;83(5):567‐75. - PubMed

Additional references

Amato 2011
    1. Amato L, Minozzi S, Davoli M, Vecchi S, Ferri M, Mayet S. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. Cochrane Database of Systematic Reviews 2011, Issue 9. [DOI: 10.1002/14651858.CD005031.pub2] - DOI - PubMed
Amato 2013
    1. Amato L, Davoli M, Ferri M, Ali R. Methadone at tapered doses for the management of opioid withdrawal. Cochrane Database of Systematic Reviews 2013, Issue 2. [DOI: 10.1002/14651858.CD003409.pub4] - DOI - PubMed
Bearn 1999
    1. Bearn J, Gossop M, Strang J. Rapid opiate detoxification treatments. Drug and Alcohol Review 1999;18(1):75‐81.
Boyce 2003
    1. Boyce SH, Armstrong PA, Stevenson J. Effect of inappropriate naltrexone use in a heroin misuser. Emergency Medicine Journal 2003;20(4):381‐2. [MEDLINE: ] - PMC - PubMed
Broers 2000
    1. Broers B, Giner F, Dumont P, Mino A. Inpatient opiate detoxification in Geneva: follow‐up at 1 and 6 months. Drug and Alcohol Dependence 2000;58(1):85‐92. - PubMed
Day 2005
    1. Day E, Ison J, Strang J. Inpatient versus other settings for detoxification for opioid dependence. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD004580.pub2] - DOI - PubMed
Farrell 1994
    1. Farrell M. Opiate withdrawal. Addiction 1994;89(11):1471‐5. - PubMed
Galloway 1993
    1. Galloway G. Heroin withdrawal precipitated by non medical use of naltrexone. American Journal of Psychiatry 1993;150(2):347‐8. - PubMed
Gossop 1988
    1. Gossop M. Clonidine and the treatment of the opiate withdrawal syndrome. Drug and Alcohol Dependence 1988;21(3):253‐9. - PubMed
Gossop 1989
    1. Gossop M, Green L, Phillips G, Bradley B. Lapse, relapse and survival among opiate addicts after treatment. A prospective follow‐up study. British Journal of Psychiatry 1989;154:348‐53. - PubMed
Gossop 1990
    1. Gossop M. The development of a short opiate withdrawal scale (SOWS). Addictive Behaviors 1990;15(5):487‐90. - PubMed
Gowing 2010
    1. Gowing L, Ali R, White J. Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD002022.pub3] - DOI - PubMed
Gowing 2015
    1. Gowing LR, Ali RL, Allsop S, Marsden J, Turf EE, West R, et al. Global statistics on addictive behaviours: 2014 status report. Addiction 2015;110(6):904‐19. [DOI: 10.1111/add.12899] - DOI - PubMed
Gowing 2016
    1. Gowing L, Farrell M, Ali R, White J. Alpha2‐adrenergic agonists for the management of opioid withdrawal. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD002024.pub5] - DOI - PubMed
Gowing 2017
    1. Gowing L, Ali R, White J. Buprenorphine for managing opioid withdrawal. Cochrane Database of Systematic Reviews 2017, Issue 2. [DOI: 10.1002/14651858.CD002025.pub5] - DOI - 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(7650):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(4):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.
Kleber 1982
    1. Kleber HD, Riordan CE. The treatment of narcotic withdrawal: a historical review. Journal of Clinical Psychiatry 1982;43(6):30‐4. - PubMed
Lipton 1983
    1. Lipton D, Maranda M. Detoxification from heroin dependency: an overview of method and effectiveness. Advances in Alcohol and Substance Abuse 1983;2(1):31‐55.
Mannelli 1999
    1. Mannelli P, Risio S, Pozzi G, Janiri L, Giacomo M. Serendipitous rapid detoxification from opiates: the importance of time‐dependent processes. Addiction 1999;94(4):589‐91. - PubMed
Mark 2001
    1. Mark TL, Woody GE, Juday T, Kleber HD. The economic costs of heroin addiction in the United States. Drug and Alcohol Dependence 2001;61(2):195‐206. [MEDLINE: ] - PubMed
Mattick 1996
    1. Mattick RP, Hall W. Are detoxification programmes effective?. Lancet 1996;347(8994):97‐100. - PubMed
Minozzi 2006
    1. Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD001333.pub4] - DOI - PubMed
Minozzi 2014
    1. Minozzi S, Amato L, Davoli M. Detoxification treatments for opiate dependent adolescents. Cochrane Database of Systematic Reviews 2014, Issue 4. [DOI: 10.1002/14651858.CD006749.pub3] - DOI - PMC - PubMed
Oxman 2004
    1. Oxman AD, GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328(19):1490‐4. - PMC - PubMed
Phillips 1986
    1. Phillips GT, Gossop M, Bradley B. The influence of psychological factors on the opiate withdrawal syndrome. British Journal of Psychiatry 1986;149(2):235‐8. [MEDLINE: ] - PubMed
Preston 1985
    1. Preston KL, Bigelow GE. Pharmacological advances in addiction treatment. International Journal of the Addictions 1985;20(6‐7):845‐67. [MEDLINE: ] - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Satel 1993
    1. Satel SL, Kosten TR, Schuckit MA, Fischman MW. Should protracted withdrawal from drugs be included in DSM‐IV?. American Journal of Psychiatry 1993;150(5):695‐704. [MEDLINE: ] - PubMed
Simon 1997
    1. Simon DL. Rapid opioid detoxification using opioid antagonists: history, theory and the state of the art. Journal of Addictive Diseases 1997;16(1):103‐22. - PubMed
Sullivan 2007
    1. Sullivan MA, Garawi F, Bisaga A, Comer SD, Carpenter K, Raby WN, et al. Management of relapse in naltrexone maintenance for heroin dependence. Drug and Alcohol Dependence 2007;91(2):289‐92. - PMC - PubMed
Tetrault 2009
    1. Tetrault JM, O'Connor PG. Management of opioid intoxication and withdrawal. In: Ries RK, Fiellin DA, Miller SC, Siatz R editor(s). Principles of Addiction Medicine. 4th Edition. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009:589‐606.
Tornabene 1974
    1. Tornabene VW. Narcotic withdrawal syndrome caused by naltrexone. Annals of Internal Medicine 1974;81(6):785‐7. - PubMed
Tucker 2000
    1. Tucker TK, Ritter AJ. Naltrexone in the treatment of heroin dependence: a literature review. Drug and Alcohol Review 2000;19(1):73‐82.
Vaillant 1988
    1. Vaillant GE. What can long‐term follow‐up teach us about relapse and prevention of relapse in addiction?. British Journal of Addiction 1988;83(10):1147‐57. - PubMed
Wells 2010
    1. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, et al. The Newcastle‐Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta‐analyses. www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed 10 March 2015).

References to other published versions of this review

Gowing 2000
    1. Gowing L, Ali R, White J. Opioid antagonists and adrenergic agonists for the management of opioid withdrawal. Cochrane Database of Systematic Reviews 2000, Issue 2. - PubMed
Gowing 2002
    1. Gowing L, Ali R, White J. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database of Systematic Reviews 2002, Issue 2. - PubMed
Gowing 2006
    1. Gowing L, Ali R, White J. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database of Systematic Reviews 2006, Issue 1. - PubMed
Gowing 2009
    1. Gowing L, Ali R, White J. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.cd002021.pub3] - DOI - PubMed

MeSH terms