Methadone at tapered doses for the management of opioid withdrawal.

BACKGROUND Despite widespread use in many countries of tapered methadone for detoxification from opiate dependence, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated. OBJECTIVES To determine whether tapered methadone is effective to manage opioids withdrawal. SEARCH STRATEGY We searched: the Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; Internet (NIDA, Clinical Trials.org, BMJ). SELECTION CRITERIA All randomised controlled trials focused on tapered methadone (length of treatment max 30 days) versus all other pharmacological detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal. DATA COLLECTION AND ANALYSIS One reviewer (LA) assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between reviewers. Where possible analysis was carried out according to the "intention to treat" principles. MAIN RESULTS 20 studies were included in the review, with 1357 participants. 10 studies compared methadone with adrenergic agonists, 7 studies compared different modalities of methadone detoxification, 2 studies compared methadone with other opioid agonists, 1 study with chlordiazepoxide, 1 with placebo. The conclusions of the 10 studies that compared methadone with adrenergic agonists showed no substantial clinical difference of the two treatments in terms of retention in treatment, degree of discomfort and detoxification success rates. The conclusions of the 6 studies that compare different methadone reduction schedules, showed that different types of methadone withdrawal schedule produce different responses in terms of withdrawal symptoms and severity of them. Regarding the studies that compare methadone with other opioid agonists, methadyl acetate performed similarly to methadone on most process and outcome measures, while methadone reduced severity of withdrawal and had fewer drop-outs than did propoxyphene. Using chlordiazepoxide vs methadone, the results suggest that the two drugs had similar results in terms of overall effectiveness. Comparing methadone with placebo more severe withdrawal and more drop outs were founded in the placebo group. The results indicate that tapered methadone and other medications used in the included studies are effective in the treatment of the heroin withdrawal syndrome, although symptoms experienced by subjects differed according to the medication used and the program adopted. It seems that regardless of which medication is selected for heroin detoxification, the rates of subsequent heroin abstinence are about equal. This suggests that the medications are similar in terms of overall effectiveness. Improvements were achieved when other services such as counseling and other supporting services were offered contemporaneously with detoxification. REVIEWERS' CONCLUSIONS Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. Results of many outcomes could not be summarised because they were presented either in graphical form or provided only statistical tests and p-values. For most studies standard deviation for continuous variables were not provided. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, accompanied by medical supervision and ancillary medications can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use. However this cannot be considered a goal for a detoxification as heroin dependence is a chronic, relapsing disorder and the goal of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.

[1]  P. McNamee,et al.  Pilot randomised controlled trial of community pharmacy administration of buprenorphine versus methadone , 2006 .

[2]  M. Amanatkar,et al.  TRAMADOL VERSUS METHADONE FOR THE MANAGEMENT OF ACUTE OPIOID WITHDRAWAL: AN ADD-ON STUDY , 2006 .

[3]  S. Darke,et al.  Outcomes after detoxification for heroin dependence: findings from the Australian Treatment Outcome Study (ATOS). , 2006, Drug and alcohol review.

[4]  H. Nadeem,et al.  Abstinence-oriented treatment for opiate addiction , 2006, British Journal of Psychiatry.

[5]  M. Greenwald Early impact of methadone induction for heroin dependence: differential effects of two dose sequences in a randomized controlled study. , 2006, Experimental and clinical psychopharmacology.

[6]  A. Byrne,et al.  Is methadone too dangerous for opiate addiction?: Methadone is still needed in addiction treatments , 2006, BMJ : British Medical Journal.

[7]  Long-ming Lei,et al.  Treatment of heroinism with acupuncture at points of the Du Channel. , 2005, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan.

[8]  P. O'Connor,et al.  The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment? , 2005, Drug and alcohol dependence.

[9]  H. Emrich,et al.  Mood and affect during detoxification of opiate addicts: a comparison of buprenorphine versus methadone , 2005, Addiction biology.

[10]  M. Branchey,et al.  Efficacy of Buspirone in the Treatment of Opioid Withdrawal , 2005, Journal of clinical psychopharmacology.

[11]  J. Neale,et al.  Recent life problems and non-fatal overdose among heroin users entering treatment. , 2005, Addiction.

[12]  S. Seiler,et al.  [Buprenorphine and methadone to opiate addicts--a randomized trial]. , 2005, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[13]  W. Schreiber,et al.  Buprenorphin oder Methadon im Entzug junger Opiatabhängiger , 2004 .

[14]  G. Gerra,et al.  Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome. , 2004, Drug and alcohol dependence.

[15]  R. Laheij,et al.  Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences , 2003, Addiction biology.

[16]  W. Ling,et al.  The Clinical Opiate Withdrawal Scale (COWS) , 2003, Journal of psychoactive drugs.

[17]  R. Chaisson,et al.  Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. , 2003, Drug and alcohol dependence.

[18]  H. Emrich,et al.  Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone. , 2002, Pharmacopsychiatry.

[19]  M. Farrell,et al.  Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone. , 2002, Drug and alcohol dependence.

[20]  M. Casas,et al.  Methadone tapering plus amantadine to detoxify heroin-dependent inpatients with or without an active cocaine use disorder: two randomised controlled trials. , 2001, Drug and alcohol dependence.

[21]  H. W. Clark,et al.  Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial. , 2000, JAMA.

[22]  G. Gerra,et al.  Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance. , 2000, Journal of substance abuse treatment.

[23]  D. Cook,et al.  Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? , 1998, The Lancet.

[24]  J. Strang,et al.  Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification. , 1998, Drug and alcohol dependence.

[25]  B. Rounsaville,et al.  Three Methods of Opioid Detoxification in a Primary Care Setting , 1997, Annals of Internal Medicine.

[26]  J. Strang,et al.  Type of hospital setting and treatment outcome with heroin addicts , 1997, British Journal of Psychiatry.

[27]  F. Forastiere,et al.  A persistent rise in mortality among injection drug users in Rome, 1980 through 1992. , 1997, American journal of public health.

[28]  J. Strang,et al.  Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. , 1996, Drug and alcohol dependence.

[29]  W. Hall,et al.  Are detoxification programmes effective? , 1996, The Lancet.

[30]  D. Rennie,et al.  The Cochrane Collaboration. Preparing, maintaining, and disseminating systematic reviews of the effects of health care. , 1995, JAMA.

[31]  J. Gray,et al.  Craving and drug reward: a comparison of methadone and clonidine in detoxifying opiate addicts. , 1995, Drug and alcohol dependence.

[32]  M. Gossop,et al.  Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients. , 1994, Journal of substance abuse treatment.

[33]  R. Baxter,et al.  Participation in an outreach-based coupon distribution program for free methadone detoxification. , 1993, Hospital & community psychiatry.

[34]  M. Stitzer,et al.  Dose-Response Effects of Methadone in the Treatment of Opioid Dependence , 1993, Annals of Internal Medicine.

[35]  J. Jaffe,et al.  A controlled trial of buprenorphine treatment for opioid dependence. , 1992, JAMA.

[36]  J. Strang,et al.  Should opiate addicts be involved in controlling their own detoxification? A comparison of fixed versus negotiable schedules. , 1991, British journal of addiction.

[37]  C. Brewin,et al.  Patient preferences and randomised clinical trials. , 1989, BMJ.

[38]  J. Strang,et al.  Opiate Withdrawal Symptoms in Response to 10-Day and 21-Day Methadone Withdrawal Programmes , 1989, British Journal of Psychiatry.

[39]  M. Gossop,et al.  Lapse, Relapse and Survival among Opiate Addicts after Treatment , 1989, British Journal of Psychiatry.

[40]  G. Vaillant What can long-term follow-up teach us about relapse and prevention of relapse in addiction? , 1988, British journal of addiction.

[41]  M. Gossop,et al.  Effects of information on the opiate withdrawal syndrome. , 1988, British journal of addiction.

[42]  H. Lei,et al.  Assessment of opioid dependence with naloxone. , 1988, British journal of addiction.

[43]  W. Bickel,et al.  A clinical trial of buprenorphine: Comparison with methadone in the detoxification of heroin addicts , 1988, Clinical pharmacology and therapeutics.

[44]  M. Gossop,et al.  The development of an opiate withdrawal scale (OWS). , 1987, British journal of addiction.

[45]  J. Camí,et al.  Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin , 1985, Clinical pharmacology and therapeutics.

[46]  D. Charney,et al.  Clonidine in outpatient detoxification from methadone maintenance. , 1985, Archives of general psychiatry.

[47]  B. Rounsaville,et al.  Success and Failure at Outpatient Opioid Detoxification: Evaluating the Process of Clonidine‐ and Methadone‐Assisted Withdrawal , 1985, The Journal of nervous and mental disease.

[48]  W. Fleischhacker,et al.  Preliminary results of guanfacine treatment of acute opiate withdrawal. , 1984, The American journal of psychiatry.

[49]  B. Rounsaville,et al.  Relationship of depression to clonidine detoxification of opiate addicts. , 1984, Comprehensive psychiatry.

[50]  M. Stitzer,et al.  Methadone detoxification: effects of methadone dose versus time in treatment. , 1984, NIDA research monograph.

[51]  R. Rawson,et al.  Efficacy of psychotherapeutic counselling during 21-day ambulatory heroin detoxification. , 1983, NIDA research monograph.

[52]  D. Lipton,et al.  DETOXIFICATION FROM HEROIN DEPENDENCY , 1982 .

[53]  A. Hasegawa,et al.  Clinical comparison of propoxyphene napsylate and methadone in the treatment of opiate dependence. , 1982, NIDA research monograph.

[54]  W. Hargreaves,et al.  Withdrawal from heroin in three or six weeks. Comparison of methadyl acetate and methadone. , 1982, Archives of general psychiatry.

[55]  Washton Am,et al.  Clonidine vs. methadone for opiate detoxification: double-blind outpatient trials. , 1981 .

[56]  A. Washton,et al.  CLONIDINE VERSUS METHADONE FOR OPIATE DETOXIFICATION , 1980, The Lancet.

[57]  S. Hall,et al.  Contingency management and information feedback in outpatient heroin detoxification , 1979 .

[58]  F. Tennant,et al.  Detoxification from methadone maintenance: double-blind comparison of two methods. , 1978, Drug and alcohol dependence.

[59]  B. Lal,et al.  Experiences of a methadone detoxification programme for opium addicts. , 1976, Drug and alcohol dependence.

[60]  G. Edwards THE ALCOHOLIC DOCTOR A Case of Neglect , 1975, The Lancet.

[61]  F. Tennant,et al.  Heroin detoxification. A comparison of propoxyphene and methadone. , 1975, JAMA.

[62]  J. Jaffe,et al.  Methadyl acetate vs methadone. A double-blind study in heroin users. , 1972, JAMA.

[63]  A. Goldstein Heroin addiction and the role of methadone in its treatment. , 1972, Archives of general psychiatry.

[64]  W. Feuerlein,et al.  [Drug addiction and drug abuse]. , 1969, Munchener medizinische Wochenschrift.

[65]  Haertzen Ca,et al.  Opiate withdrawal as measured by the Addiction Research Center Inventory (ARCI). , 1968 .

[66]  C. Himmelsbach Clinical Studies of Drug Addiction. Physical Dependence, Withdrawal and Recovery. , 1942 .

[67]  C. Himmelsbach THE MORPHINE ABSTINENCE SYNDROME, ITS NATURE AND TREATMENT* , 1941 .

[68]  L. Goodman,et al.  THE PHARMACOLOGICAL BASIS OF THERAPEUTICS , 1966 .

[69]  Cheng Wufu Clinical Research of Withdrawal Syndrome Treatment with Phenytoin in Heroin Addicts , 2006 .

[70]  Z. Xiaoling Controlled Clinical Study on Paiduyangsheng Capsule in Detoxification of Heroin Abuse , 2006 .

[71]  L. Degenhardt,et al.  Heroin use In Australia: its impact on public health and public order , 1999 .

[72]  M. Passeri,et al.  Clonidine and opiate receptor antagonists in the treatment of heroin addiction. , 1995, Journal of substance abuse treatment.

[73]  D. Tusel,et al.  Methadone transition treatment: a treatment model for 180-day methadone detoxification. , 1995, The International journal of the addictions.

[74]  W. Hall,et al.  Key issues in methadone maintenance treatment , 1992 .

[75]  M. Torrens,et al.  Assessment and management of opioid withdrawal symptoms in buprenorphine-dependent subjects. , 1992, British journal of addiction.

[76]  M. Porta,et al.  Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial. , 1990, British journal of addiction.

[77]  J. Strang,et al.  Comparison of linear versus inverse exponential methadone reduction curves in the detoxification of opiate addicts. , 1990, Addictive behaviors.

[78]  J. Gray,et al.  The effects of exposure to drug-related cues in detoxified opiate addicts: a theoretical review and some new data. , 1990, Addictive behaviors.

[79]  M. Gossop,et al.  The development of a Short Opiate Withdrawal Scale (SOWS). , 1990, Addictive behaviors.

[80]  D. Turkington,et al.  Chlordiazepoxide vs. methadone in opiate withdrawal: a preliminary double blind trial. , 1989, Drug and alcohol dependence.

[81]  M. Porta,et al.  Success and failure at inpatient heroin detoxification. , 1989, British journal of addiction.

[82]  L. Handelsman,et al.  Two new rating scales for opiate withdrawal. , 1987, The American journal of drug and alcohol abuse.

[83]  M. Gossop,et al.  An investigation of withdrawal symptoms shown by opiate addicts during and subsequent to a 21-day in-patient methadone detoxification procedure. , 1987, Addictive behaviors.

[84]  G. Singer,et al.  Opiate-seeking behavior under conditions of methadone detoxification and removal. , 1986, The International journal of the addictions.

[85]  B. Rounsaville,et al.  Comparison of clinician ratings to self reports of withdrawal during clonidine detoxification of opiate addicts. , 1985, The American journal of drug and alcohol abuse.

[86]  J. van Ree,et al.  Des-Gly9-[Arg8]-vasopressin may facilitate methadone detoxification of heroin addicts. , 1983, Substance and alcohol actions/misuse.

[87]  D. Desmond,et al.  Outpatient methadone withdrawal for heroin dependence. , 1980, The American journal of drug and alcohol abuse.

[88]  W. Hargreaves,et al.  Detoxification from heroin using self vs physician regulation of methadone dose. , 1979, The International journal of the addictions.

[89]  J. Mintz,et al.  Double-blind detoxification of methadone maintenance patients. , 1975, The International journal of the addictions.

[90]  H. Lôo,et al.  [A French experience with methadone]. , 1975, L'Encephale.

[91]  L. Kolb,et al.  CLINICAL STUDIES OF DRUG ADDICTION, III , 1938 .