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
. 2016 May 3;2016(5):CD002024.
doi: 10.1002/14651858.CD002024.pub5.

Alpha₂-adrenergic agonists for the management of opioid withdrawal

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

Alpha₂-adrenergic agonists for the management of opioid withdrawal

Linda Gowing et al. Cochrane Database Syst Rev. .

Abstract

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

Objectives: To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists compared with placebo, reducing doses of methadone, symptomatic medications, or an alpha2-adrenergic agonist regimen different to the experimental intervention, for the management of the acute phase of opioid withdrawal. Outcomes included the withdrawal syndrome experienced, duration of treatment, occurrence of adverse effects, and completion of treatment.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to November week 2, 2015), EMBASE (January 1985 to November week 2, 2015), PsycINFO (1806 to November week 2, 2015), Web of Science, and reference lists of articles.

Selection criteria: Randomised controlled trials comparing alpha2-adrenergic agonists (clonidine, lofexidine, guanfacine, tizanidine) with reducing doses of methadone, symptomatic medications or placebo, or comparing different alpha2-adrenergic agonists to modify the signs and symptoms of withdrawal in participants who were opioid dependent.

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

Main results: We included 26 randomised controlled trials involving 1728 participants. Six studies compared an alpha2-adrenergic agonist with placebo, 12 with reducing doses of methadone, four with symptomatic medications, and five compared different alpha2-adrenergic agonists. We assessed 10 studies as having a high risk of bias in at least one of the methodological domains that were considered.We found moderate-quality evidence that alpha2-adrenergic agonists were more effective than placebo in ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57; 3 studies; 148 participants). We found moderate-quality evidence that completion of treatment was significantly more likely with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to 2.84; 3 studies; 148 participants).Peak withdrawal severity may be greater with alpha2-adrenergic agonists than with reducing doses of methadone, as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73; 5 studies; 340 participants; low quality), and peak withdrawal score (standardised mean difference (SMD) 0.22, 95% CI -0.02 to 0.46; 2 studies; 263 participants; moderate quality), but these differences were not significant and there is no significant difference in severity when considered over the entire duration of the withdrawal episode (SMD 0.13, 95% CI -0.24 to 0.49; 3 studies; 119 participants; moderate quality). The signs and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic agonists. The duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95% CI -1.31 to -0.83; 3 studies; 310 participants; low quality). Hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10; 6 studies; 464 participants; low quality), but there was no significant difference in rates of completion of withdrawal treatment (RR 0.85, 95% CI 0.69 to 1.05; 9 studies; 659 participants; low quality).There were insufficient data for quantitative comparison of different alpha2-adrenergic agonists. Available data suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.

Authors' conclusions: Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. We detected no significant difference in efficacy between treatment regimens based on clonidine or lofexidine and those based on reducing doses of methadone over a period of around 10 days, but methadone was associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.

PubMed Disclaimer

Conflict of interest statement

Linda Gowing: None known.

Michael Farrell: None known.

Robert Ali: The review author's institution has received untied educational grants from Reckitt Benckiser to conduct scientific research and convene scientific meetings. No personal fees were paid to the review author.

Jason M White: None known.

Figures

1
1
Study flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Alpha2‐adrenergic agonist versus placebo, Outcome 1 Peak withdrawal score.
1.2
1.2. Analysis
Comparison 1 Alpha2‐adrenergic agonist versus placebo, Outcome 2 Participants with severe withdrawal.
1.3
1.3. Analysis
Comparison 1 Alpha2‐adrenergic agonist versus placebo, Outcome 3 Completion of treatment.
2.1
2.1. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 1 Peak withdrawal score.
2.2
2.2. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 2 Participants with severe withdrawal.
2.3
2.3. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 3 Overall withdrawal severity.
2.4
2.4. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 4 Duration of treatment.
2.5
2.5. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 5 Number experiencing hypotensive or other adverse effects.
2.6
2.6. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 6 Drop‐out due to adverse effects.
2.7
2.7. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 7 Completion of treatment.
2.8
2.8. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 8 Completion of treatment by opioid.
2.9
2.9. Analysis
Comparison 2 Alpha2‐adrenergic agonist versus methadone, Outcome 9 Completion of treatment by setting.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Batey 1987 {published data only}
    1. Batey R, Liddle C, Craig P. A placebo controlled trial of clonidine in the outpatient management of heroin withdrawal. Australian Drug and Alcohol Review 1987;6(1):11‐4.
Bearn 1996 {published data only}
    1. Bearn J, Gossop M, Strang J. Randomised double‐blind comparison of lofexidine and methadone in the in‐patient treatment of opiate withdrawal. Drug and Alcohol Dependence 1996;43(1‐2):87‐91. - PubMed
Benos 1985 {published data only}
    1. Benos VJ. Clonidine in opiate withdrawal syndrome [Clonidin beim opiatentzugssyndrom]. Fortschritte der Medizin 1985;103(42):991‐5. - PubMed
Bertschy 1997 {published data only}
    1. Bertschy G, Bryois C, Bondolfi G, Velardi A, Budry P, Dascal D, et al. The association carbamazepine‐mianserin in opiate withdrawal: a double blind pilot study versus clonidine. Pharmacological Research 1997;35(5):451‐6. - PubMed
Bruno 1979 {published data only}
    1. Bruno F, Franceschini G. Treatment of opiate withdrawal syndrome with nonnarcotic drugs in addicts undergoing voluntary detoxication. I. Effect of clonidine [Il controllo della sindrome d'astinenza immediata da oppiacei con farmaci ad azione non narcotica in soggetti tossico‐dipendenti in disintossicazione volontaria. (1) Prime valutazioni cliniche sull'efficacia della clonidina]. Lavoro Neuropsichiatrico 1979;65(1‐2):1‐15.
Cami 1985 {published data only}
    1. Camí J, Torres S, San L, Solé À, Guerra D, Ugena B. Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin. Clinical Pharmacology and Therapeutics 1985;38(3):336‐41. - PubMed
Carnwath 1998 {published data only}
    1. Carnwath T, Hardman J. Randomised double‐blind comparison of lofexidine and clonidine in the out‐patient treatment of opiate withdrawal. Drug and Alcohol Dependence 1998;50(3):251‐4. - 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
Gupta 1988 {published data only}
    1. Gupta AK, Jha BK. Clonidine in heroin withdrawal syndrome: a controlled study in India. British Journal of Addiction 1988;83(9):1079‐84. - PubMed
Howells 2002 {published and unpublished data}
    1. Howells C, Allen S, Gupta J, Farrell M. A double blind study comparing the efficacy of methadone and lofexidine in the treatment of opiate detoxification in prisoners at HMP Winchester. Britannia Pharmaceuticals Ltd 1999.
    1. Howells C, Allen S, Gupta J, Stillwell G, Marsden J, Farrell M. Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone. Drug and Alcohol Dependence 2002;67(2):169‐76. - PubMed
Jiang 1993 {published data only}
    1. Jiang Z. Rapid detoxification with clonidine for heroin addiction: a comparative study on its efficacy vs methadone. Chinese Journal of Neurology and Psychiatry 1993;26(1):10‐3.
Kahn 1997 {published data only}
    1. Kahn A, Mumford JP, Rogers GA, Beckford H. Double‐blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Drug and Alcohol Dependence 1997;44(1):57‐61. - PubMed
Kleber 1985 {published and unpublished data}
    1. Kleber HD, Riordan CE, Rounsaville B, Kosten T, Charney D, Gaspari J, et al. Clonidine in outpatient detoxification from methadone maintenance. Archives of General Psychiatry 1985;42(4):391‐4. - PubMed
    1. Kosten TR, Rounsaville BJ, Kleber HD. Comparison of clinician ratings to self reports of withdrawal during clonidine detoxification of opiate addicts. American Journal of Drug and Alcohol Abuse 1985;11(1‐2):1‐10. - PubMed
    1. Kosten TR, Rounsaville BJ, Kleber HD. Relationship of depression to clonidine detoxification of opiate addicts. Comprehensive Psychiatry 1984;25(5):503‐8. - PubMed
    1. Rounsaville BJ, Kosten T, Kleber H. Success and failure at outpatient opioid detoxification: evaluating the process of clonidine and methadone assisted withdrawal. Journal of Nervous and Mental Disease 1985;173(2):103‐10. - PubMed
Li 2002 {published data only}
    1. Li M, Chen K, Mo Z. Use of qigong therapy in the detoxification of heroin addicts. Alternative Therapies in Health and Medicine 2002;8(1):50‐9. - PubMed
Lin 1997 {published data only}
    1. Lin S‐K, Strang J, Su L‐W, Tsai C‐J, Hu W‐H. Double‐blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal. Drug and Alcohol Dependence 1997;48(2):127‐33. - PubMed
Muga 1990 {published data only}
    1. Muga R, Tor J, Forteza‐Rei J, Jacas C, Altes J, Mestre L. Comparative effectiveness of alpha‐2 adrenergic agonists (clonidine and guanfacine) in the hospital detoxification of opiate addicts [Eficacia comparada de agonistas alpha2‐adrenergicos (clonidina‐guanfacina) en la desintoxicacion hospitalaria de adictos a opiaceos]. Medicina Clinica 1990;94(5):169‐72. [MEDLINE: ] - PubMed
Nazari 2013 {published data only}
    1. Nazari SM, Naseri M, Mokri A, Davati A, Kamalinejad M. Hab‐o Shefa (an Iranian traditional medicine compound) in withdrawal syndrome and its effects in acute detoxification of opiates addict: a randomized, double blind, clinical trials. Journal of Medicinal Plant Research 2013;7(22):1628‐35.
San 1990 {published data only}
    1. Cami J, Gilabert M, San L, Torre R. Hypercortisolism after opioid discontinuation in rapid detoxification of heroin addicts. British Journal of Addiction 1992;87(8):1145‐51. - PubMed
    1. San L, Camí J, Peri JM, Mata R, Porta M. Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial. British Journal of Addiction 1990;85(1):141‐7. - PubMed
    1. San L, Peri JM, Mata R, Porta M. Success and failure at inpatient heroin detoxification. British Journal of Addiction 1989;84(1):81‐7. - PubMed
San 1994 {published data only}
    1. San L, Fernández T, Camí J, Gossop M. Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin‐addicted patients. Journal of Substance Abuse Treatment 1994;11(5):463‐9. - PubMed
Senay 1983 {unpublished data only}
    1. Senay E, Tennant FS, Washton AM. [Boehringer Ingelheim GmbH report number U85‐0844]. Boehringer Ingelheim Pty Ltd 1983.
Sos 2000 {published data only}
    1. Sos I, Kiss N, Csorba J, Gerevich J. Tizanidine in the treatment of acute withdrawal symptoms in heroin dependent patients [A tizanidin hatekonysaga heroinfuggo betegek akut megvonasi tuneteinek kezeleseben]. Orvosi Hetilap 2000;141(15):783‐6. - PubMed
Umbricht 2003 {published data only}
    1. Umbricht A, Hoover DR, Tucker MJ, Leslie JM, Chaisson RE, Preston KL. Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin‐dependent patients with HIV infection. Drug and Alcohol Dependence 2003;69(3):263‐72. - PubMed
Vilalta 1987 {published data only}
    1. Vilalta J, Treserra J, Garcia‐Esteve L, Garcia‐Giralt M, Cirera E. Methadone, clonidine and levomepromazine in the treatment of opiate abstinence syndrome: double‐blind clinical trial in heroin‐addicted patients admitted to a general hospital for organic pathology [Metadona, clonidina y levomepromacina en el tratamiento del sindrome de abstinencia a opiaceos: ensayo clinico a doble ciego en pacientes heroinomanos ingresados por patologia organica en un hospital general]. Medicina Clinica 1987;88(17):674‐6. [MEDLINE: ] - PubMed
Washton 1981 {published data only}
    1. Washton AM, Resnick RB. Clonidine for opiate detoxification ‐ outpatient clinical trials. American Journal of Psychiatry 1980;137(9):1121‐2. - PubMed
    1. Washton AM, Resnick RB. Clonidine versus methadone for opiate detoxification. The Lancet 1980;2(8207):1297. - PubMed
    1. Washton AM, Resnick RB. Clonidine vs methadone for opiate detoxification: double‐blind outpatient trials. In: Harris LS editor(s). Problems of Drug Dependence, 1980. Proceedings of the 42nd Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Washington D.C.: Department of Health and Human Services, 1981.
    1. Washton AM, Resnick RB, Rawson RA. Clonidine hydrochloride: a nonopiate treatment for opiate withdrawal. NIDA Research Monograph 1979;27:233‐9. - PubMed
Yu 2008 {published data only}
    1. Yu E, Miotto K, Akerele E, Montgomery A, Elkashef A, Walsh R, et al. A Phase 3 placebo‐controlled, double‐blind, multi‐site trial of the alpha‐2‐adrenergic agonist, lofexidine, for opioid withdrawal. Drug and Alcohol Dependence 2008;97:158‐68. - PMC - PubMed
    1. Yu E, Miotto K, Akerele E, O'Brien CP, Ling W, Kleber H, et al. Clinical pharmacokinetics of lofexidine, the alpha 2‐adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis. American Journal of Drug and Alcohol Abuse 2008;34(5):611‐6. - PubMed

References to studies excluded from this review

Akhondzadeh 2000 {published data only}
    1. Ahmadi‐Abhari SA, Akhondzadeh S, Assadi SM, Shabestari OL, Farzanehgan ZM, Kamlipour A. Baclofen versus clonidine in the treatment of opiates withdrawal, side‐effects aspect: a double‐blind randomized controlled trial. Journal of Clinical Pharmacy and Therapeutics 2001;26(1):67‐71. - PubMed
    1. Akhondzadeh S, Ahmadi‐Abhari SA, Assadi SM, Shabestari OL, Kashani AR, Farzanehgan ZM. Double‐blind randomised controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal. Journal of Clinical Pharmacy and Therapeutics 2000;25(5):347‐53. - PubMed
Batey 1985 {published data only}
    1. Batey R. Outpatient detoxification in heroin users ‐ a comparison of a hemineurin and a clonidine regime. Australian Alcohol/Drug Review 1985;4(1):53‐5.
Bearn 1998 {published data only}
    1. Bearn J, Gossop M, Strang J. Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in‐patient opiate detoxification. Drug and Alcohol Dependence 1998;50:227‐32. - 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;8:49‐57. - PubMed
Casey 1988 {unpublished data only}
    1. Casey PR, Tomiak RHH. Clonidine in opiate withdrawal. Boehringer Ingelheim Ltd 1988.
Chattopadhyay 2010 {published data only}
    1. Chattopadhyay S, Singh OP, Bhattacharyya A, Sen S, Roy P, Debnath S. Tramadol versus clonidine in management of heroin withdrawal. Asian Journal of Psychiatry 2010;3(4):237‐9. - PubMed
Cheskin 1994 {published and unpublished data}
    1. Cheskin LJ, Fudala PJ, Johnson RE. A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids. Drug and Alcohol Dependence 1994;36(2):115‐21. [MEDLINE: ] - PubMed
Chuang 1999 {published data only}
    1. Chuang L, Jing L, Mingsheng H. The treatment of clonidine for opiate withdrawal symptoms. Chinese Journal of Psychiatry 1999;32(2):103‐5.
Day 2011 {published data only}
    1. Day E, Strang J. Outpatient versus inpatient opioid detoxification: a randomized controlled trial. Journal of Substance Abuse Treatment 2011;40(1):56‐66. - PubMed
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. [EMBASE: 2001291795] - PubMed
Ghodse 1994 {published data only}
    1. Ghodse H, Myles J, Smith SE. Clonidine is not a useful adjunct to methadone gradual detoxification in opioid addiction. British Journal of Psychiatry 1994;165(3):370‐4. - PubMed
Gold 1978 {published data only}
    1. Gold MS, Redmond DE, Kleber HD. Clonidine blocks acute opiate‐withdrawal symptoms. The Lancet 1978;2(8090):599‐600. [MEDLINE: ] - PubMed
Gold 1979 {published data only}
    1. Gold MS, Redmond DE, Kleber HD. Noradrenergic hyperactivity in opiate withdrawal supported by clonidine reversal of opiate withdrawal. American Journal of Psychiatry 1979;136(1):100‐2. [MEDLINE: ] - PubMed
Gold 1980a {published data only}
    1. Gold MS, Pottash ALC, Sweeney DR, Kleber HD. Effect of methadone dosage on clonidine detoxification efficacy. American Journal of Psychiatry 1980;137(3):375‐6. [MEDLINE: ] - PubMed
Gold 1980b {published data only}
    1. Gold MS, Kleber HD. Clinical utility of clonidine in opiate withdrawal: a study of 100 patients. Progress in Clinical and Biological Research 1981;71:299‐306. - PubMed
    1. Gold MS, Pottash AL, Sweeney DR, Davies RK, Kleber HD. Clonidine decreases opiate withdrawal‐related anxiety: possible opiate noradrenergic interaction in anxiety and panic. Substance and Alcohol Actions/Misuse 1980;1(2):239‐46. - PubMed
Gossop 1989 {published data only}
    1. Gossop M. The detoxification of high dose heroin addicts in Pakistan. Drug and Alcohol Dependence 1989;24(2):143‐50. - PubMed
Hartmann 1991 {published data only}
    1. Hartmann F, Poirier M‐F, Bourdel M‐C, Loo H, LeComte J‐M, Schwartz J‐C. Comparison of Acetophen with clonidine for opiate withdrawal symptoms. American Journal of Psychiatry 1991;148(5):627‐9. [MEDLINE: ] - PubMed
Huertas 1995 {published data only}
    1. Huertas D, Lopez‐Gomez I, Chamorro L, Martin M. A new combined treatment for opioid detoxification: the association between dextropropoxyphene and guanfacine [Nueva pauta combinada para la desintoxicacion de opiaceos: la linea DG]. Revista de Psiquiatria de la Facultad de Medicina de Barcelona 1995;22(5):109‐13. [PsycINFO 1996‐86268‐001]
Janiri 1994 {published data only}
    1. Janiri L, Mannelli P, Persico AM, Serretti A, Tempesta E. Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine. Drug and Alcohol Dependence 1994;36(2):139‐45. [MEDLINE: ] - PubMed
Jasinski 1985 {published data only}
    1. Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal: differential effects on signs and symptoms. Archives of General Psychiatry 1985;42(11):1063‐6. [MEDLINE: ] - PubMed
Jimenez‐Lerma 2002 {published data only}
    1. Jimenez‐Lerma JM, Landabaso M, Iraurgi I, Calle R, Sanz J, Gutierrez‐Fraile M. Nimodipine in opiate detoxification: a controlled trial. Addiction 2002;97(7):819‐24. - PubMed
Kasvikis 1990 {published data only}
    1. Kasvikis Y, Bradley B, Gossop M, Griffiths P, Marks I. Clonidine versus long and short term methadone aided withdrawal from opiates: an uncontrolled comparison. International Journal of the Addictions 1990;25(10):1169‐78. [MEDLINE: ] - PubMed
Lerner 1995 {published data only}
    1. Lerner AG, Gelkopf M, Oyffe I, Sigal M. Home‐based inpatient treatment vs outpatient day clinic treatment: a preliminary report in opiate‐dependent patients. Journal of Nervous and Mental Disease 1995;183(11):715. - PubMed
Lin 2014 {published data only}
    1. Lin S‐K, Pan C‐H, Chen C‐H. A double‐blind, placebo‐controlled trial of dextromethorphan combined with clonidine in the treatment of heroin withdrawal. Journal of Clinical Psychopharmacology 2014;34(4):508‐12. - PubMed
Malhotra 1997 {published data only}
    1. Malhotra A, Basu D, Chintalapudi M, Mattoo SK, Varma VK. Clonidine versus withdrawal using an opioid in in‐patient opioid detoxification. European Addiction Research 1997;3:146‐9.
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. [MEDLINE: ] - PubMed
    1. O'Connor PG, Waugh ME, Schottenfeld RS, Diakogiannis IA, Rounsaville BJ. Ambulatory opiate detoxification and primary care: a role for the primary care physician. Journal of General Internal Medicine 1992;7(5):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 randomised trial. Annals of Internal Medicine 1997;127(7):526‐30. [MEDLINE: ] - 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 Series 1993;132:309.
Ockert 2011 {published data only}
    1. Ockert DM, Volpicelli JR, Baier Jr AR, Coons EE, Fingesten A. A nonopioid procedure for outpatient opioid detoxification. Journal of Addiction Medicine 2011;5(2):110‐4. - PubMed
Pini 1991 {published data only}
    1. Pini LA, Sternieri E, Ferretti C. Dapiprazole compared with clonidine and a placebo in detoxification of opiate addicts. International Journal of Clinical Pharmacology Research 1991;11(2):99‐105. [MEDLINE: ] - PubMed
    1. Pini LA, Sternieri E, Ferretti C. Dapiprazole versus clonidine and versus placebo in detoxification of opiate addicts. European Journal of Pharmacology 1990;183(2):209. - 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;52:368.
Strang 1997 {published data only}
    1. Dawe S, Gray JA. Craving and drug reward: a comparison of methadone and clonidine in detoxifying opiate addicts. Drug and Alcohol Dependence 1995;39(3):207‐12. - PubMed
    1. Dawe S, Powell J, Richards D, Gossop M, Marks I, Strang J, et al. Does post‐withdrawal cue exposure improve outcome in opiate addiction? A controlled trial. Addiction 1993;88(9):1233‐45. - PubMed
    1. Powell J, Dawe S, Richards D, Gossop M, Marks I, Strang J, et al. Can opiate addicts tell us about their relapse risk? Subjective predictors of clinical prognosis. Addictive Behaviors 1993;18(4):473‐90. - PubMed
    1. Strang J, Marks I, Dawe S, Powell J, Gossop M, Richards D, et al. Type of hospital setting and treatment outcome with heroin addicts. Results from a randomised trial. British Journal of Psychiatry 1997;171:335‐9. [MEDLINE: ] - PubMed
Wilson 1993 {published data only}
    1. Wilson RS, diGeorge WS. Methadone combined with clonidine versus clonidine alone in opiate detoxification. Journal of Substance Abuse Treatment 1993;10(6):529‐35. [MEDLINE: ] - PubMed
Wylie 1995 {published data only}
    1. Wylie AS, Stewart AM. Lofexidine based regimen for opiate addicts. British Journal of General Practice 1995;45(393):217‐8. [MEDLINE: ] - PMC - PubMed

Additional references

Akhurst 1999
    1. Akhurst JS. The use of lofexidine by drug dependency units in the United Kingdom. European Addiction Research 1999;5:43‐9. [MEDLINE: ] - PubMed
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
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. [MEDLINE: ] - PubMed
Gold 1980c
    1. Gold MS, Pottash AC, Sweeney DR, Kleber HD. Opiate withdrawal using clonidine. A safe, effective, and rapid nonopiate treatment. JAMA 1980;243(4):343‐6. - PubMed
Gold 1989
    1. Gold MS, Pottash AC. The neurobiological implications of clonidine HCl. Annals of the New York Academy of Science 1989;362:191‐202. - PubMed
Gossop 1988a
    1. Gossop M. Clonidine and the treatment of the opiate withdrawal syndrome. Drug and Alcohol Dependence 1988;21(3):253‐9. - PubMed
Gossop 1989b
    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
Gowing 2009a
    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
Gowing 2009b
    1. Gowing L, Ali R, White J. Buprenorphine for the management of opioid withdrawal. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD002025.pub4] - DOI
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
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
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.
Mark 2001
    1. Mark TL, Woody GE, Juday T, Kleber HD. The economic costs of heroin addiction in the United States. Drug & Alcohol Dependence 2001;61(2):195‐206. [MEDLINE: ] - PubMed
Mattick 1996
    1. Mattick RP, Hall W. Are detoxification programmes effective?. The Lancet 1996;347:97‐100. - 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
Phillips 1986
    1. Phillips GT, Gossop M, Bradley B. The influence of psychological factors on the opiate withdrawal syndrome. British Journal of Psychiatry 1986;149:235‐8. [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. - PubMed
Sheridan 1999
    1. Sheridan J, Cook C, Strang J. Audit of the in‐patient management of opioid withdrawal using lofexidine hydrochloride. Journal of Substance Use 1999;4(1):29‐34. [CINAHL 1999061746]
Spencer 1989
    1. Spencer L, Gregory M. Clonidine transdermal patches for use in outpatient opiate withdrawal. Journal of Substance Abuse Treatment 1989;6:113‐7. [MEDLINE: ] - 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.
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
World Drug Report 2013
    1. United Nations Office on Drugs and Crime. World Drug Report 2013. www.unodc.org/unodc/secured/wdr/wdr2013/World_Drug_Report_2013.pdf (accessed 18 March 2014).

Publication types

MeSH terms

LinkOut - more resources