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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 We sought published/unpublished randomised controlled trials (RCTs) from authors., Selection Criteria: Randomised controlled trials of buprenorphine maintenance treatment versus placebo or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.

Background: The evidence of tapered methadone's efficacy in managing opioid withdrawal has been systematically evaluated in the previous version of this review that needs to be updated, Objectives: To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate., Search Methods: We searched: Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 4), PubMed (January 1966 to May 2012), EMBASE (January 1988 to May 2012), CINAHL (2003- December 2007), PsycINFO (January 1985 to December 2004), reference lists of articles., Selection Criteria: All randomised controlled trials that focused on the use of tapered methadone versus all other pharmacological detoxification treatments or placebo for the treatment of opiate withdrawal., Data Collection and Analysis: Two review authors assessed the included studies. Any doubts about how to rate the studies were resolved by discussion with a third review author. Study quality was assessed according to the criteria indicated in the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: Twenty-three trials involving 2467 people were included. Comparing methadone versus any other pharmacological treatment, we observed no clinical difference between the two treatments in terms of completion of treatment, 16 studies 1381 participants, risk ratio (RR) 1.08 (95% confidence interval (CI) 0.97 to 1.21); number of participants abstinent at follow-up, three studies, 386 participants RR 0.98 (95% CI 0.70 to 1.37); degree of discomfort for withdrawal symptoms and adverse events, although it was impossible to pool data for the last two outcomes. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (eight studies), anxiolytic (two studies), paiduyangsheng (one study). Comparing methadone with placebo (two studies) more severe withdrawal and more drop-outs were found in the placebo group. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted., Authors' Conclusions: Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long- acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.

Treatment is effective in reducing heroin use and clinical and social problems among heroin addicts. The effectiveness is related to the duration of treatment. "VEdeTTE" is an Italian longitudinal study funded by the Ministry of Health to evaluate the effectiveness of treatments provided by the National Health Services. The study involved 115 drug treatment centers and 10,454 heroin users. Clinical and personal information were collected at intake through a structured interview. Treatments were recorded using a standardized form. Survival analysis and Cox Proportional Hazard model were used to evaluate treatment retention. Five thousand four hundred and fifty-seven patients who started a treatment in the 18 months of the study were included in the analysis: 43.2% received methadone maintenance therapy (MMT), 10.5% therapeutic community, and 46.3% abstinence-oriented therapy (AOT). The likelihood of remaining in treatment was 0.5 at 179 days. The median daily dose of methadone was 37 mg. Psychotherapy was provided in 7.6% of patients receiving methadone and 4.9% of those in therapeutic community. Type of therapy was the strongest predictor of retention, with AOT showing the lowest retention. In MMT patients, retention improved according to dose. Living alone, psychiatric comorbidity and cocaine use increased the risk of dropout. Psychotherapy associated halved the risk of dropout.

Background: Methadone maintenance was the first widely used opioid replacement therapy to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed., Objectives: To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence., Search Strategy: We searched the following databases up to Dec 2008: the Cochrane Controlled Trials Register, EMBASE, PubMED, CINAHL, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs., Selection Criteria: All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence., Data Collection and Analysis: Reviewers evaluated the papers separately and independently, rating methodological quality of sequence generation, concealment of allocation and bias. Data were extracted independently for meta-analysis and double-entered., Main Results: Eleven studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 1969 participants. The sequence generation was inadequate in one study, adequate in five studies and unclear in the remaining studies. The allocation of concealment was adequate in three studies and unclear in the remaining studies. Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment and in the suppression of heroin use as measured by self report and urine/hair analysis (6 RCTs, RR = 0.66 95% CI 0.56-0.78), but not statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25) or mortality (4 RCTs, RR=0.48; 95%CI: 0.10-2.39)., Authors' Conclusions: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity or mortality.

Background: Buprenorphine has been reported as an alternative to methadone for maintenance treatment of opioid dependence, but differing results are reported concerning its relative effectiveness indicating the need for an integrative review., Objectives: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use., Search Strategy: We searched the following databases up to October 2006: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK , Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library of Congress databases, reference lists of identified studies and reviews, authors were asked about any other published or unpublished relevant RCT., Selection Criteria: Randomised clinical trials of buprenorphine maintenance versus placebo or methadone maintenance., Data Collection and Analysis: Authors separately and independently evaluated the papers and extracted data for meta-analysis., Main Results: Twenty four studies met the inclusion criteria (4497 participants), all were randomised clinical trials, all but six were double-blind. The method of allocation concealment was not clearly described in the majority (20) of the studies, but where it was reported the methodological quality was good. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.50; 95% CI: 1.19 - 1.88), medium (RR=1.74; 95% CI: 1.06 - 2.87), and high doses (RR=1.74; 95% CI: 1.02 - 2.96). The high statistical heterogeneity prevented the calculation of a cumulative estimate. However, only medium and high dose buprenorphine suppressed heroin use significantly above placebo. Buprenorphine given in flexible doses was statistically significantly less effective than methadone in retaining patients in treatment (RR= 0.80; 95% CI: 0.68 - 0.95), but no different in suppression of opioid use for those who remained in treatment. Low dose methadone is more likely to retain patients than low dose buprenorphine (RR= 0.67; 95% CI: 0.52 - 0.87). Medium dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for medium dose buprenorphine over medium dose methadone in retention (RR=0.79; 95% CI:0.64 - 0.99) and medium dose buprenorphine was inferior in suppression of heroin use., Authors' Conclusions: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is less effective than methadone delivered at adequate dosages.

Background: Methadone at appropriate doses has been demonstrated to be the most effective means for retaining patients in treatment and suppressing heroin use., Aim: To describe the modalities of day-to-day provision of methadone maintenance treatments (MMT) in Italian public health centres and to analyze the duration of MMTs by dose and by association with psychosocial treatments., Patients and Methods: We analyzed 8,378 subjects, 18 years of age or over, enrolled between September 1998 and March 2001 in one of 115 public treatment centres for heroin dependence in Italy. Treatment data were collected for each subject from enrolment to the end of the study period (maximum of 18 months)., Results: Of the total of 29,495 treatments delivered, 21.0% were methadone maintenance, and 34.4% were methadone detoxification. Fifty percent of MMTs offered had a mean dose less than or equal to 40 mg/day, and only 19% had doses higher than or equal to 60 mg/day; treatments with doses higher than 60 mg/day lasted longer than treatments with lower doses. Differences in treatment length were observed between MMTs associated with a psychosocial treatment and those offered alone, only for doses <60 mg/day., Conclusions: In Italy, MMTs are delivered at inappropriate doses in more than 80% of the cases. The increase of methadone doses to adequate levels as indicated by the literature is necessary to ensure proper and effective use of MMTs in public treatment centres for heroin users.

Aims: To identify factors associated with entering any methadone treatment at first admission at an NHS treatment centre in Italy and to investigate determinants of receiving detoxification or maintenance methadone treatments., Methods: Data were analysed from 565 heroin addicts who entered for the first time one of 90 NHS treatment centres in 12 Italian regions between September 1998 and March 2001. Subjects were interviewed at admission by the centre's staff and followed-up for 18 months. Details on treatments provided were recorded using a standardised form. Random effects logistic regression analysis was applied., Results: Factors positively associated with any methadone treatment assignment were: being younger than 25 years and using heroin more than twice a day, having been recently incarcerated, and living with a partner. Independent predictors of admission to methadone maintenance were injecting heroin, having sex without a condom in the previous six months, being HIV positive and having been enrolled at a NHS TC where a psychiatrist was present. Using heroin once a day or more and using cocaine were factors associated with enrollment into detoxification treatment. A significant heterogeneity between centres was observed., Conclusions: Results from this study give an insight into different patient profiles who are enrolled in methadone treatments. The observed heterogeneity between centres indicates the need to develop and implement common guidelines for the access of heroin addicts to substitution treatment.

Background: Despite widespread use in many countries the evidence of tapered methadone's efficacy in managing opioid withdrawal has not been systematically evaluated., Objectives: To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate., Search Strategy: We searched: Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (January 1966 to December 2004), EMBASE (January 1988 to December 2004), PsycINFO (January 1985 to December 2004), and reference lists of articles. We also contacted manufacturers and researchers in the field., Selection Criteria: All randomised controlled trials which focus on the use of tapered methadone versus all other pharmacological detoxification treatments or placebo for the treatment of opiate withdrawal., Data Collection and Analysis: Two reviewers assessed the included studies. Any doubt about how to rate the studies were resolved by discussion with a third reviewer. Study quality was assessed according to the criteria indicated in Cochrane Reviews Handbook 4.2. (Alderson 2004), Main Results: Sixteen trials involving 1187 people were included. Comparing methadone versus any other pharmacological treatment we observed no clinical difference between the two treatments in terms of completion of treatment, relative risk (RR) 1.12; 95% CI 0.94 to 1.34 and results at follow-up RR 1.17; 95% CI 0.72 to 1.92. It was impossible to pool data for the other outcomes but the results of the studies did not show significant differences between the considered treatments. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (four studies), chlordiazepoxide (study). Comparing methadone with placebo (one study) more severe withdrawal and more drop outs were found in the placebo group. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted., Authors' Conclusions: Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. 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.

Aim: To summarize the major findings of the five Cochrane reviews on substitution maintenance treatments for opioid dependence., Methods: We conducted a narrative and quantitative summary of systematic review findings. There were 52 studies included in the original reviews (12,075 participants, range 577-5894): methadone maintenance treatment (MMT) was compared with methadone detoxification treatment (MDT), no treatment, different dosages of MMT, buprenorphine maintenance treatment (BMT), heroin maintenance treatment (HMT), and l-alpha-acetylmethadol (LAAM) maintenance treatment (LMT)., Measurements: Outcomes considered were retention in treatment, use of heroin and other drugs during treatment, mortality, criminal activity, and quality of life., Findings: Retention in treatment: MMT is more effective than MDT, no treatment, BMT, LMT, and heroin plus methadone. MMT proved to be less effective than injected heroin alone. High doses of methadone are more effective than medium and low doses. Use of heroin: MMT is more effective than waiting list, less effective than LAAM, and not different from injected heroin. No significant results were available for mortality and criminal activity., Conclusions: These findings confirm that MMT at appropriate doses is the most effective in retaining patients in treatment and suppressing heroin use but show weak evidence of effectiveness toward other relevant outcomes. Future clinical trials should collect data on a broad range of health outcomes and recruit participants from heterogeneous practice settings and social contexts to increase generalizability of results.

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.

Background: Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review., Objectives: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use., Search Strategy: We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT., Selection Criteria: Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence., Data Collection and Analysis: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered., Main Results: Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo., Reviewers' Conclusions: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Background: Methadone maintenance was the first widely used form of opioid replacement therapy developed to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed., Objectives: To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence., Search Strategy: We searched all the following databases up to 2001: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs., Selection Criteria: All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence., Data Collection and Analysis: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation, data were extracted independently for meta-analysis and double-entered., Main Results: Six studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 954 participants. The method of concealment of allocation was inadequate in one study, not clearly described in four studies, but adequate in a sixth study. Based on the meta-analysis, methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patient in treatment (3 RCTs, RR=3.05; 95%CI: 1.75-5.35) and in the suppression of heroin use (3 RCTs, RR=0.32; 95%CI: 0.23-0.44), but not statistically in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25)., Reviewer's Conclusions: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity.

Background: Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review., Objectives: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use., Search Strategy: We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT., Selection Criteria: Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence., Data Collection and Analysis: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered., Main Results: Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo., Reviewer's Conclusions: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Background: Despite widespread use 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 withdrawal from opioids., Search Strategy: We searched: 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; Internet (NIDA, Clinical Trials.org, BMJ)., Selection Criteria: All RCT which focus on the use of tapered methadone (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 assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between reviewers. Qualitative assessments of the methodology of studies were carried out using validated checklists. Where possible analysis was carried out according to the "intention to treat" principles., Main Results: 20 studies were included in the review, with 1357 people randomised. Comparisons: 10 studies methadone with adrenergic agonists, 7 studies different modalities of methadone detoxification, 2 studies methadone with other opioid agonists, 1 study methadone with chlordiazepoxide, 1 with placebo. The conclusions of the 10 studies that compared methadone with adrenergic agonists showed a 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 modalities produce different responses in terms of time course of withdrawal, severity of withdrawal response and in terms of subsequent engagement with treatment. 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 a propoxyphene group. Using chlordiazepoxide vs methadone, the two drugs had similar results in terms of overall effectiveness. Comparing methadone with placebo more severe withdrawal and more drop outs 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. 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., Reviewer's 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.

Retention in treatment among 1503 heroin users attending public treatment centres in 1995 was studied. Three different treatments were considered: methadone maintenance, drug-free program and naltrexone. The retention rate after 1 year was 40% for patients in methadone maintenance, 18% in naltrexone and 15% in drug-free program. For patients in maintenance, methadone dosage and clinic policy were the most important factors for retention. Patients taking > or = 60 mg/day and 30-59 mg/day were respectively 70 and 50% more likely to remain in treatment than those receiving a < 30 mg daily dose. Patients in maintenance-oriented clinics were 30% more likely to remain in treatment than those in abstinence-oriented centres.