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Introduction and Aims: To corroborate protective effects of a range of drug treatment modalities against overdose mortality risk., Design and Methods: Nested case-control study, with incidence density sampling, selecting controls retrospectively at each case event. Cases and controls came from a sub-cohort of opioid-dependent patients (n = 4444) from two Italian regions (Lazio and Piedmont). From 1998 to 2005, there were 91 overdose deaths (cases) matched to 352 controls. The primary outcome was overdose mortality and the primary exposure was drug treatment: opioid agonist treatment (OAT), opioid detoxification, residential community, psychosocial and other pharmacological treatment. Conditional logistic regression models generated intervention effects comparing mortality risk in and out of treatment, adjusting for confounding variables., Results: Overall, drug treatment reduced overdose mortality risk by 80% [adjusted odds ratio (AOR) 0.18, 95% confidence interval (CI) 0.10-0.33, P < 0.001] compared to being out of treatment. There was a particularly strong protective effect of OAT on overdose mortality (AOR 0.08, 95% CI 0.03-0.23, P < 0.001) compared to being out of treatment. There was evidence of a substantially elevated risk of overdose in the first month of leaving treatment (AOR 23.50, 95% CI 7.84-70.19, P < 0.001) compared to being in treatment., Discussion and Conclusions: The nested case-control design strengthened earlier findings that OAT in Italy has strong protective effects on overdose mortality risk, much stronger than has been previously seen in other Western European settings., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

Background: The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013., Objectives: To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances., Search Methods: We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs)., Selection Criteria: Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane., Main Results: We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate-quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low-quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;-530.00 g, 95%CI -662.78 to -397.22 (one study, 19 particpants) and MD: -215.00 g, 95%CI -238.93 to -191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low-quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI -0.03 to 0.03, two studies,163 participants, low-quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low-quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low-quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low-quality evidence). Methadone versus slow-release morphine: There were no dropouts in either treatment group. Oral slow-release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low-quality evidence). In the comparison between methadone and slow-release morphine, no side effects were reported for the mother. In contrast, one child in the methadone group had central apnoea, and one child in the morphine group had obstructive apnoea (low-quality evidence)., Authors' Conclusions: Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid-dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow-release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background and Aims: The World Health Organization (WHO), and a growing number of other organizations, have adopted the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system in order to both assess the quality of research evidence and develop clinical practice guidelines. In 2009 WHO published a guideline on psychosocially assisted pharmacological treatment of opioid dependence, based on the results of Cochrane Reviews summarized using the GRADE methodology. The main features of this system are an a priori definition of outcomes and their relevance, and distinction between the quality of evidence (also referred to as confidence in the estimate of intervention effect) and the strength of recommendations. We consider how successful this approach has been., Analysis and Evidence: We discuss the merits and limitations of using Cochrane Reviews and GRADE framework in developing guidelines in the field of drug addiction. In 2009 a panel of multi-disciplinary international experts identified 15 clinical questions and eight relevant outcomes. Cochrane reviews were available for each clinical question and four outcomes. The panel formulated 15 recommendations. Eight recommendations were classified as strong, two of which were based on high-quality evidence and three on very low-quality evidence. For example, the strong recommendation to use methadone in adequate doses in preference to buprenorphine was based on high-quality evidence, while the strong recommendation not to use the combination of opioid antagonists with heavy sedation in the management of opioid withdrawal was based on low-quality evidence., Conclusions: An explicit stepwise process of moving from evaluation of the quality of evidence to the definition of the strength of recommendations is important in providing practical and clear clinical guidance for practitioners and policy-makers in addiction., (© 2014 Society for the Study of Addiction.)

Background: The scientific literature examining effective treatments for opioid-dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component. Nevertheless, no reviews have been published that systematically assess the effectiveness of pharmacological maintenance treatment in adolescents., Objectives: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for retaining adolescents in treatment, reducing the use of substances and improving health and social status., Search Methods: We searched the Cochrane Drugs and Alcohol Group's Trials Register (January 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINAHL (January 1982 to January 2014), Web of Science (1991 to January 2014) and reference lists of articles., Selection Criteria: Randomised and controlled clinical trials of any maintenance pharmacological interventions either alone or associated with psychosocial intervention compared with no intervention, placebo, other pharmacological intervention, pharmacological detoxification or psychosocial intervention in adolescents (13 to 18 years)., Data Collection and Analysis: We used the standard methodological procedures expected by The Cochrane Collaboration., Main Results: We included two trials involving 189 participants. One study, with 35 participants, compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment lasting 16 weeks, after which patients were detoxified. The other study, with 154 participants, compared maintenance treatment with buprenorphine-naloxone and detoxification with buprenorphine. We did not perform meta-analysis because the two studies assessed different comparisons.In the study comparing methadone and LAAM, the authors declared that there was no difference in the use of a substance of abuse or social functioning (data not shown). The quality of the evidence was very low. No side effects, such as nausea, vomiting, constipation, weakness or fatigue, were reported by study participants.In the comparison between buprenorphine maintenance and buprenorphine detoxification, maintenance treatment appeared to be more efficacious in retaining patients in treatment (drop-out risk ratio (RR) 0.37; 95% confidence interval (CI) 0.26 to 0.54), but not in reducing the number of patients with a positive urine test at the end of the study (RR 0.97; 95% CI 0.78 to 1.22). Self reported opioid use at one-year follow-up was significantly lower in the maintenance group, even though both groups reported a high level of opioid use (RR 0.73; 95% CI 0.57 to 0.95). More patients in the maintenance group were enrolled in other addiction treatment programmes at 12-month follow-up (RR 1.33; 95% CI 0.94 to 1.88). The quality of the evidence was low. No serious side effects attributable to buprenorphine-naloxone were reported by study participants and no patients were removed from the study due to side effects. The most common side effect was headache, which was reported by 16% to 21% of patients in both groups, Authors' Conclusions: It is difficult to draft conclusions on the basis of only two trials. One of the possible reasons for the lack of evidence could be the difficulty of conducting trials with young people for practical and ethical reasons.There is an urgent need for further randomised controlled trials comparing maintenance treatment with detoxification treatment or psychosocial treatment alone before carrying out studies that compare different pharmacological maintenance treatments. These studies should have long follow-up and measure relapse rates after the end of treatment and social functioning (integration at school or at work, family relationships).

Background: The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless, no studies have been published that systematically assess the effectiveness of the pharmacological detoxification among adolescents., Objectives: To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared with no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status., Search Methods: We searched the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINHAL (January 1982 to January 2014), Web of Science (1991-January 2014) and reference lists of articles., Selection Criteria: Randomised controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13 to 18 years)., Data Collection and Analysis: We used standard methodological procedures recommended by The Cochrane Collaboration, Main Results: Two trials involving 190 participants were included. One trial compared buprenorphine with clonidine for detoxification. No difference was found for drop out: risk ratio (RR) 0.45 (95% confidence interval (CI): 0.20 to 1.04) and acceptability of treatment: withdrawal score mean difference (MD): 3.97 (95% CI -1.38 to 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 (95% CI 1.58 to 76.55), quality of evidence moderate.The other trial compared maintenance treatment versus detoxification treatment: buprenorphine-naloxone maintenance versus buprenorphine detoxification. For drop out the results were in favour of maintenance treatment: RR 2.67 (95% CI 1.85, 3.86), as well as for results at follow-up RR 1.36 [95% CI 1.05to 1.76); no differences for use of opiate, quality of evidence low., Authors' Conclusions: It is difficult to draw conclusions on the basis of two trials with few participants. Furthermore, the two studies included did not consider the efficacy of methadone that is still the most frequent drug utilised for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people due to practical and ethical reasons.

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 prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Heroin crosses the placenta and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome., Objectives: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for child health status, neonatal mortality, retaining pregnant women in treatment and reducing the use of substances., Search Methods: We searched the Cochrane Drugs and Alcohol Group Trials Register (September 2013), PubMed (1966 to September 2013), CINAHL (1982 to September 2013), reference lists of relevant papers, sources of ongoing trials, conference proceedings and national focal points for drug research. We contacted authors of included studies and experts in the field., Selection Criteria: Randomised controlled trials assessing the efficacy of any maintenance pharmacological treatment for opiate-dependent pregnant women., Data Collection and Analysis: We used the standard methodological procedures expected by The Cochrane Collaboration., Main Results: We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high drop-out rate (30% to 40%) and this was unbalanced between groups.Methadone versus buprenorphine: the drop-out rate from treatment was lower in the methadone group (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.41 to 1.01, three studies, 223 participants). There was no statistically significant difference in the use of primary substance between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.69, two studies, 151 participants). For both, we judged the quality of evidence as low. Birth weight was higher in the buprenorphine group in the two trials that could be pooled (mean difference (MD) -365.45 g (95% CI -673.84 to -57.07), two studies, 150 participants). The third study reported that there was no statistically significant difference. For APGAR score neither of the studies which compared methadone with buprenorphine found a significant difference. For both, we judged the quality of evidence as low. Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, did not differ significantly between groups. We judged the quality of evidence as very low.Methadone versus slow-release morphine: there was no drop-out in either treatment group. Oral slow-release morphine seemed superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants). We judged the quality of evidence as moderate.Only one study which compared methadone with buprenorphine reported side effects. For the mother there was no statistically significant difference; for the newborns in the buprenorphine group there were significantly fewer serious side effects.In the comparison between methadone and slow-release morphine no side effects were reported for the mother, whereas one child in the methadone group had central apnoea and one child in the morphine group had obstructive apnoea., Authors' Conclusions: We did not find sufficient significant differences between methadone and buprenorphine or slow-release morphineto allow us to conclude that one treatment is superior to another for all relevant outcomes. While methadone seems superior in terms of retaining patients in treatment, buprenorphine seems to lead to less severe neonatal abstinence syndrome. Additionally, even though a multi-centre, international trial with 175 pregnant women has recently been completed and its results published and included in this review, the body of evidence is still too small to draw firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.

Aims: To assess the incidence or prevalence of opioid dependence syndrome in adults (with and without previous history of substance abuse) following treatment with opioid analgesics for pain relief., Methods: Medline, Embase, CINHAL and the Cochrane Library were searched up to January 2011. Systematic reviews and primary studies were included if they reported data about incidence or prevalence of opioid dependence syndrome (as defined by DSM-IV or ICD-10) in patients receiving strong opioids (or opioid-type analgesics) for treatment of acute or chronic pain due to any physical condition. The data were abstracted, and the methodological quality was assessed using validated checklists., Results: Data were extracted from 17 studies involving a total of 88 235 participants. The studies included three systematic reviews, one randomized controlled trial, eight cross-sectional studies and four uncontrolled case series. Most studies included adult patients with chronic non-malignant pain; two also included patients with cancer pain; only one included patients with a previous history of dependence. Incidence ranged from 0 to 24% (median 0.5%); prevalence ranged from 0 to 31% (median 4.5%)., Conclusions: The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

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.

Background: Maintenance treatments are effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of additional psychosocial services., Objectives: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus standard agonist treatment for opiate dependence, Search Strategy: We searched the Cochrane Drugs and Alcohol Group trials register (June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2011), PUBMED (1996 to 2011); EMBASE (January 1980 to 2011); CINAHL (January 2003 to 2011); PsycINFO (1985 to 2003) and reference list of articles., Selection Criteria: Randomised controlled trials and controlled clinical trial comparing any psychosocial plus any agonist with any agonist alone for opiate dependence., Data Collection and Analysis: Two authors independently assessed trial quality quality and extracted data., Main Results: 35 studies, 4319 participants, were included. These studies considered thirteen different psychosocial interventions. Comparing any psychosocial plus any maintenance pharmacological treatment to standard maintenance treatment, results do not show benefit for retention in treatment, 27 studies, 3124 participants, RR 1.03 (95% CI 0.98 to 1.07), abstinence by opiate during the treatment, 8 studies, 1002 participants, RR 1.12 (95% CI 0.92 to 1.37), compliance, three studies, MD 0.43 (95% CI -0.05 to 0.92), psychiatric symptoms, 3 studies, MD 0.02 (-0.28 to 0.31), depression, 3 studies, MD -1.70 (95% CI -3.91 to 0.51) and results at the end of follow up as number of participants still in treatment, 3 studies, 250 participants, RR 0.90 (95% CI 0.77 to 1.07) and participants abstinent by opioid, 3 studies, 181 participants, RR 1.15 (95% CI 0.98 to 1.36). Comparing the different psychosocial approaches, results are never statistically significant for all the comparisons and outcomes., Authors' Conclusions: For the considered outcomes, it seems that adding any psychosocial support to standard maintenance treatments do not add additional benefits. Data do not show differences also for contingency approaches, contrary to all expectations. Duration of the studies was too short to analyse relevant outcomes such as mortality. It should be noted that the control intervention used in the studies included in the review on maintenance treatments, is a program that routinely offers counselling sessions in addition to methadone; thus the review, actually, did not evaluate the question of whether any ancillary psychosocial intervention is needed when methadone maintenance is provided, but the narrower question of whether a specific more structured intervention provides any additional benefit to a standard psychosocial support. These interventions probably can be measured and evaluated by employing diverse criteria for evaluating treatment outcomes, aimed to rigorously assess changes in emotional, interpersonal, vocational and physical health areas of life functioning.

Background: Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological rather than physiological symptoms associated with the withdrawal syndrome., Objectives: To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status., Search Strategy: We searched the Cochrane Drugs and Alcohol Group trials register (June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 6, 2011), PUBMED (1996 to June 2011); EMBASE (January 1980 to June 2011); CINAHL (January 2003 to June 2008); PsycINFO (1985 to April 2003) and reference list of articles., Selection Criteria: Randomised controlled trials and controlled clinical trial which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded., Data Collection and Analysis: Two authors independently assessed trials quality and extracted data., Main Results: Eleven studies, 1592 participants, fulfilled the criteria of inclusion and were included in the review. The studies considered five different psychosocial interventions and two pharmacological treatments (methadone and buprenorphine). Compared to any pharmacological treatment alone, the association of any psychosocial with any pharmacological was shown to significantly reduce dropouts RR 0.71 (95% CI 0.59 to 0.85), use of opiate during the treatment, RR 0.82 (95% CI 0.71 to 0.93), at follow up RR 0.66 (95% IC 0.53 to 0.82) and clinical absences during the treatment RR 0.48 (95%CI 0.38 to 0.59). Moreover, with the evidence currently available, there are no data supporting a single psychosocial approach., Authors' Conclusions: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, participants abstinent at follow-up and clinical attendance. The evidence produced by this review is limited due to the small number of participants included in the studies, the heterogeneity of the assessment or the lack of detailed outcome information that prevented the possibility of cumulative analysis for several outcomes. Nevertheless it seems desirable to develop adjunct psychosocial approaches that might make detoxification more effective.

Background: Research on clinical application of oral naltrexone agrees on several things. From a pharmacological perspective, naltrexone works. From an applied perspective, the medication compliance and the retention rates are poor., Objectives: To evaluate the effects of naltrexone maintenance treatment versus placebo or other treatments in preventing relapse in opioid addicts after detoxification., Search Strategy: We searched: Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library issue 6 2010), PubMed (1973- June 2010), CINAHL (1982- June 2010). We inspected reference lists of relevant articles and contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups., Selection Criteria: All randomised controlled clinical trials which focus on the use of naltrexone maintenance treatment versus placebo, or other treatments to reach sustained abstinence from opiate drugs, Data Collection and Analysis: Three reviewers independently assessed studies for inclusion and extracted data. One reviewer carried out the qualitative assessments of the methodology of eligible studies using validated checklists., Main Results: Thirteen studies, 1158 participants, met the criteria for inclusion in this review.Comparing naltrexone versus placebo or no pharmacological treatments, no statistically significant difference were noted for all the primary outcomes considered. The only outcome statistically significant in favour of naltrexone is re incarceration, RR 0.47 (95%CI 0.26-0.84), but results come only from two studies. Considering only studies were patients were forced to adherence a statistical significant difference in favour of naltrexone was found for retention and abstinence, RR 2.93 (95%CI 1.66-5.18).Comparing naltrexone versus psychotherapy, in the two considered outcomes, no statistically significant difference was found in the single study considered.Naltrexone was not superior to benzodiazepines and to buprenorphine for retention and abstinence and side effects. Results come from single studies., Authors' Conclusions: The findings of this review suggest that oral naltrexone did not perform better than treatment with placebo or no pharmacological agent with respect to the number of participants re-incarcerated during the study period. If oral naltrexone is compared with other pharmacological treatments such as benzodiazepine and buprenorphine, no statistically significant difference was found. The percentage of people retained in treatment in the included studies is however low (28%). The conclusion of this review is that the studies conducted have not allowed an adequate evaluation of oral naltrexone treatment in the field of opioid dependence. Consequently, maintenance therapy with naltrexone cannot yet be considered a treatment which has been scientifically proved to be superior to other kinds of treatment.

Background: Lifetime prevalence of depression in subjects with opioid dependence is higher than in the general population (44-54% versus 16%) and represents a risk factor for morbidity and mortality. For patients on opioid agonist treatment, current prevalence rates of depression ranges between 10 and 30%, influencing negatively the outcome of the treatment., Objectives: To evaluate the efficacy and the acceptability of antidepressants for the treatment of depressed opioid dependents treated with opioid agonists., Search Strategy: We searched Pubmed, EMBASE, CINAHL (to October 2009), CENTRAL (The Cochrane Library Cochrane Drug and Alcohol Group Specialised Register, issue 4, 2009), main electronic sources of ongoing trials, specific trial databases and reference lists of all relevant papers., Selection Criteria: Randomised and controlled clinical trials examining the efficacy of any antidepressant medication to treat depressed opioid dependents in treatment with opioid agonists., Data Collection and Analysis: Two authors independently screened and extracted data from studies., Main Results: Seven studies, 482 participants, met the inclusion criteria.- Comparing antidepressant with placebo, no statistically significant results for dropouts. Selecting studies with low risk of bias, 325 participants, results favour placebo, RR 1.40 (Cl 95% 1.00 to 1.96). For severity of depression, results from two studies, 183 participants, favour antidepressants utilising Clinical Global Impression Scale RR 1.92 (CI 95% 1.26 to 2.94), while another study, 95 participants, utilising the Hamilton Depression Rating Scale, did not find a statistically significant difference RR 0.96 (CI 95% 0.54 to 1.71). For adverse events, result favour placebo, four studies, 311 participants, RR 2.90 (Cl 95% 1.23 to 6.86). For drug use, three studies, 211 participants, it was not possible to pool data because outcomes' measures were not comparable. Looking at singular studies, no statistically significant difference was seen.- Comparing different classes of antidepressants, the results favour tricyclics for severity of depression, two studies, 183 participants, RR 1.92 (Cl 95% 1.26 to 2.94) and favour placebo for adverse events, two studies, 172 participants, RR 3.11 (Cl 95% 1.06 to 9.12)., Authors' Conclusions: There is low evidence, at the present, supporting the clinical use of antidepressants for the treatment of depressed opioid addicts in treatment with opioid agonists. There is a need of larger randomised studies investigating relevant outcomes, safety issues and reporting data to allow comparison of results.

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: The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless no studies have been published which systematically assess the effectiveness of the pharmacological maintenance treatment among adolescent., Objectives: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on retaining adolescents in treatment, reducing the use of substances and reducing health and social status, Search Strategy: We searched the Cochrane Drugs and Alcohol Group's trials register (august 2008), MEDLINE (January 1966 to august 2008), EMBASE (January 1980 to august 2008), CINHAL (January 1982 to august 2008) and reference lists of articles, Selection Criteria: Randomised and controlled clinical trials comparing any maintenance pharmacological interventions alone or associated with psychosocial intervention with no intervention, placebo, other pharmacological intervention included pharmacological detoxification or psychosocial intervention in adolescent (13-18 years), Data Collection and Analysis: Two reviewers independently assessed trial quality and extracted data, Main Results: Two trials involving 187 participants were included. One study compared methadone with LAAM for maintenance treatment lasting 16 weeks after which patients were detoxified, the other compared maintenance treatment with buprenorphine - naloxone with detoxification with buprenorphine. No meta-analysis has been performed because the two studies assessed different comparisons. Maintenance treatment seems more efficacious in retaining patients in treatment but not in reducing patients with positive urine at the end of the study. Self reported opioid use at 1 year follow up was significantly lower in the maintenance group even if both group reported high level of opioid use and more patients in the maintenance group were enrolled in other addiction treatment at 12 month follow up., Authors' Conclusions: It is difficult to draft conclusions on the basis of only two trials. One of the possible reason for the lack of evidence could be the difficulty to conduct trial with young people due to practical and ethic reasons.

Background: The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless no studies have been published which systematically assess the effectiveness of the pharmacological detoxification among adolescents., Objectives: To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (August 2008), MEDLINE (January 1966 to August 2008), EMBASE (January 1980 to August 2008), CINHAL (January 1982 to August) and reference lists of articles., Selection Criteria: Randomised and controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13-18 years)., Data Collection and Analysis: Two reviewers independently assessed trial quality and extracted data., Main Results: One trial involving 36 participants was included. It compares buprenorphine with clonidine for detoxification. No difference was found for drop out: RR 0.45 (95%CI: 0.20 - 1.04) and acceptability of treatment: withdrawal score WMD: 3.97 (95%CI -1.38, 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 [95%CI 1.58, 76.55]., Authors' Conclusions: It is difficult to draft conclusions on the basis of only one trial with few participants. Furthermore, the only study included did not consider the efficacy of methadone that is still the most frequent drug utilized for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people for to practical and ethical reasons.

Background: Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological rather than physiological symptoms associated with the withdrawal syndrome., Objectives: To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status., Search Strategy: We searched the Cochrane Drugs and Alcohol Group trials register (27 February 2008). Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), PUBMED (1996 to February 2008); EMBASE (January 1980 to February 2008); CINAHL (January 2003-February 2008); PsycINFO (1985 to April 2003) and reference list of articles., Selection Criteria: Randomised controlled trials which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded., Data Collection and Analysis: Three reviewers independently assessed trials quality and extracted data., Main Results: Nine studies involving people were included. These studies considered five different psychosocial interventions and two substitution detoxification treatments: Methadone and Buprenorphine. The results show promising benefit from adding any psychosocial treatment to any substitution detoxification treatment in terms of completion of treatment relative risk (RR) 1.68 (95% confidence interval (CI) 1.11 to 2.55), use of opiate RR 0.82 (95% CI 0.71 to 0.93), results at follow-up RR 2.43 (95% CI 1.61 to 3.66), and compliance RR 0.48 (95% CI 0.38 to 0.59)., Authors' Conclusions: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, results at follow-up and compliance. Although a treatment, like detoxification, that exclusively attenuates the severity of opiate withdrawal symptoms can be at best partially effective for a chronic relapsing disorder like opiate dependence, this type of treatment is an essential step prior to longer-term drug-free treatment and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective. Limitations to this review are imposed by the heterogeneity of the assessment of outcomes. Because of lack of detailed information no meta analysis could be performed to analyse the results related to several outcomes.

Background: Maintenance treatments are effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of additional psychosocial services offered by most maintenance programs., Objectives: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus standard agonist treatment for opiate dependence in respect of retention in treatment, use of substances, health and social status., Search Strategy: We searched: Cochrane Drugs and Alcohol Group's Register of Trials (February 2008), Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library issue 1, 2008), MEDLINE (January 1966 to February 2008), EMBASE (January 1980 to February 2008), CINAHL (January 2003-February 2008), PsycINFO (January 1985 to April 2003), reference lists of articles., Selection Criteria: Randomised studies comparing any psychosocial plus any agonist with any agonist alone intervention for opiate dependence., Data Collection and Analysis: Three reviewers independently assessed trial quality and extracted data., Main Results: Twenty eight trials, 2945 participants, were included. These studies considered twelve different psychosocial interventions and three pharmacological maintenance treatments. Comparing any psychosocial plus any maintenance pharmacological treatment to standard maintenance treatment, results do not show benefit for retention in treatment, 23 studies, 2193 participants, Relative Risk (RR) 1.02 (95% CI 0.97 to 1.07), use of opiate during the treatment, eight studies, 681 participants, RR 0.86 (95% CI 0.65 to 1.13), compliance, three studies, MD 0.43 (95% CI -0.05 to 0.92), psychiatric symptoms, four studies, MD 0.02 (-0.19 to 0.23), depression, four studies, MD -1.30 (95% CI -3.31 to 0.72) and results at follow up as number of participants still in treatment at the end of the follow-up , 289 participants, RR 0.91 (95% CI 0.77 to 1.06). In spite of results at follow up as number of participants abstinent at the end of the follow-up, five studies, 232 participants, show a benefit in favour of the associated treatment RR1.15 (95% CI 1.01 to 1.32). The remaining outcomes were analysed only in single studies considering a limited number of participants.Comparing the different psychosocial approaches, results are never statistically significant for all the comparisons and outcomes., Authors' Conclusions: Results suggest that adding any psychosocial support to maintenance treatments improve the number of participants abstinent at follow up; no differences for the other outcome measures. Data do not show differences between different psychosocial interventions also for contingency approaches, contrary to all expectations. Duration of the studies was too short to analyse relevant outcomes such as 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: The prevalence of opiate use among pregnant women ranges from 1% to 2% to as much as 21%. Heroin crosses the placenta and pregnant opiate dependent women experience a six fold increase in maternal obstetric complications such as low birth weight, toxaemia, 3rd trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neurobehavioral problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome., Objectives: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on child health status, neonatal mortality, retaining pregnant women in treatment, and reducing use of substances, Search Strategy: We searched Cochrane Drugs and Alcohol Group' Register of Trials (June 2007), PubMed (1966 - June 2007), CINAHL (1982- June 2007), reference lists of relevant papers, sources of ongoing trials, conference proceedings, National focal points for drug research. Authors of included studies and experts in the field were contacted., Selection Criteria: Randomised controlled trials enrolling opiate dependent pregnant women, Data Collection and Analysis: The authors assessed independently the studies for inclusion and methodological quality. Doubts were solved by discussion., Main Results: We found three trials with 96 pregnant women. Two compared methadone with buprenorphine and one methadone with oral slow morphine. For the women there was no difference in drop out rate RR 1.00 (95% CI 0.41 to 2.44) and use of primary substance RR 2.50 (95% CI 0.11 to 54.87) between methadone and buprenorphine, whereas oral slow morphine seemed superior to methadone in abstaining women from the use of heroin RR 2.40 (95% CI 1.00 to 5.77)For the newborns in one trial buprenorphine performed better than methadone for birth weight WMD -530 gr (95% CI -662 to -397), this result is not confirmed in the other trial. For the APGAR score both studies didn't find significant difference . No differences for NAS measures used. Comparing methadone with oral slow morphine no differences for birth weight and mean duration of NAS. The APGAR score wasn't considered., Authors' Conclusions: We didn't find any significant difference between the drugs compared both for mother and for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another. There is an urgent need of big randomized controlled trials.

Objective: To estimate the mortality rates from drug-related deaths and other causes among problem drug users and population attributable risk of death due to opiate use in eight study sites in Europe., Methods: Opiate users were recruited from drug treatment centres during the period 1990-1998 and deaths followed up through national or local mortality registries. Gender-specific overall mortality rate, proportion of deaths by cause (drug-related, HIV, other), standardized mortality ratios (SMRs), and the attributable risk fraction (ARF) were estimated., Results: Crude mortality rates varied from 1 per 100 person-years in the Dublin and London cohorts to 3.8 per 100 person-years in Barcelona. The highest drug-related mortality rate was 10 per 1,000 person-years in Barcelona; the rates were approximately 7 per 1,000 person-years in Denmark, London, Rome, and Vienna, and <3.5 per 1,000 person-years for the others cohorts. The mortality rate for AIDS was <2 per 1,000 person-years in all the cohorts except Lisbon, Rome, and Barcelona, for which it was approximately 6 per 1,000 person-years. The highest SMR among males was 21.1 in Barcelona, and among females the highest SMRs were 53.7 and 37.7 in Barcelona and Rome, respectively. In Denmark the ARF was 5%, whereas it was >10% in all other study sites and 24% in Barcelona., Conclusion: Cohort mortality studies, especially in combination with estimates of prevalence, provide useful insights into the impact of opiate use on mortality across European countries and emphasize how preventing overall and drug-related deaths among opiate users can significantly improve the health of the population.

Background: Research on the clinical application of oral naltrexone agrees on several things. From a pharmacological perspective, naltrexone works. From an applied perspective, however, this medication is not used since the medication compliance and the retention rates are very poor., Objectives: To evaluate the effects of naltrexone maintenance treatment versus placebo or other treatments in preventing relapse in opioid addicts after detoxification., Search Strategy: We searched the Cochrane Drugs and Alcohol Group Register of Trials (January 2005), Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 1, 2005), MEDLINE (1973-first year of naltrexone use in humans- January 2005), EMBASE (1974- January 2005), PsycINFO (OVID-January 1985 to January 2004). We inspected reference lists of relevant articles and we contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups., Selection Criteria: All randomised and controlled clinical trials which focus on the use of naltrexone maintenance treatment versus placebo, or other treatments to reach sustained abstinence from opiate drugs, Data Collection and Analysis: Three reviewers independently assessed studies for inclusion and extracted data. One reviewer carried out the qualitative assessments of the methodology of eligible studies using validated checklists., Main Results: Ten studies, 696 participants, met the criteria for inclusion in this review. Only two studies described an adequate allocation concealment. The results show that naltrexone maintenance therapy alone or associated with psychosocial therapy is more efficacious that placebo alone or associated with psychosocial therapy in limiting the use of heroin during the treatment (RR 0,72 95% confidence interval 0.58 to 0.90). If we consider only the studies comparing naltrexone with placebo, the difference do not reach the statistical significancy, RR 0.79 (95%CI 0.59 to 1.06). With respect to the number of participants re incarcerated during the study period, the naltrexone associated with psychosocial therapy is more effective than the psychosocial treatment alone; RR 0.50 (95%CI 0.27 to 0.91). No statistically significant benefit was shown in terms of retention in treatment, side effects or relapse results at follow-up for any of the considered comparisons., Authors' Conclusions: Unfortunately the studies did not provide an objective evaluation of naltrexone treatment in the field of opioid dependence. The conclusions are also limited due to the heterogeneity of the trials both in the interventions and in the assessment of outcomes.

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: Substance dependence is a major social and public health problem; therefore it is a priority to develop effective treatments. The treatment of opioid dependence is complex. Previous Cochrane reviews have explored the efficacy of pharmacotherapy for opiate dependence. This current review focuses on the role of psychosocial interventions alone for the treatment of opiate dependence. There are many different psychosocial interventions offered to opiate addicts, which are widely spread. There is some evidence for the effectiveness of psychosocial interventions, but no systematic review has even been carried out., Objectives: To assess the efficacy and acceptability of psychosocial interventions alone for treating opiate use disorders., Search Strategy: Electronic searches of Cochrane Library, EMBASE, MEDLINE, and LILACS; reference searching; personal communication; conference abstracts; unpublished trials; book chapters on treatment of opioid abuse/ dependence., Selection Criteria: The inclusion criteria for all randomised-controlled trials were that they should focus on psychosocial interventions alone for treating opioid use disorders., Data Collection and Analysis: Reviewers extracted the data independently using relative risks, weighted mean difference and number needed to treat estimated, when possible. The reviewers assumed that people who died or dropped out had no improvement (intention to treat analysis) and tested the sensitivity of the final results to this assumption., Main Results: Five studies fit the study criteria. These analysed Contingency Management, Brief Reinforcement Based Intensive Outpatient Therapy coupled with Contingency Management, Cue Exposure therapy, Alternative Program for Methadone Maintenance Treatment Program Drop-outs (MMTP) and Enhanced Outreach-Counselling Program. All the treatments were studied against the control (standard) treatment; therefore it was not possible to identify which type of psychosocial therapy was most effective. The main findings were that both Enhanced Outreach Counselling and Brief Reinforcement Based Intensive Outpatient Therapy coupled with Contingency Management had significantly better outcomes than standard therapy within treatment. This was regarding relapse to opioid use, re-enrollment in treatment and retention in treatment. At 1-month and 3- month follow up the effects of Reinforcement Based Intensive Outpatient Therapy were not sustained. There was no further follow up of the Enhanced Outreach Counselling group. The Alternative Program for MMTP Drop-outs and the behavioural therapies of Cue Exposure and Contingency Management alone were no better than the control (standard) therapy. As the studies were heterogeneous, it was not possible to pool the results and perform a meta-analysis., Authors' Conclusions: The available evidence has low numbers and is heterogeneous. At present psychosocial treatments alone are not adequately proved treatment modalities or superior to any other type of treatment. It is important to develop a better evidence base for psychosocial interventions to assist in future rationale planning of opioid use drug treatment services. Large-scale randomised trials are required with longer follow up stating methods of randomisation, allocation concealment and blinding. Where possible this should include intention to treat analysis, with power calculations performed prior to the trial. These studies can be designed and delivered to provide usable data for better understanding of this important component of intervention in the field of dependence.

Background: Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of dependent heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological symptoms rather than physiological symptoms associated with the withdrawal syndrome., Objectives: To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status., Search Strategy: We searched the Cochrane Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of relevant articles. There were no language or publication restrictions., Selection Criteria: Randomised controlled trials which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded., Data Collection and Analysis: The trials were independently assessed for inclusion and methodological quality by three reviewers. Data were extracted independently and double checked., Main Results: The searching process resulted in the identification of 77 different studies: 8 studies met inclusion criteria. These studies considered 5 different psychosocial interventions and 2 substitution detoxification treatments: Methadone and Buprenorphine. The results show promising benefit from adding any psychosocial treatment to any substitution detoxification treatment in terms of completion of treatment RR 1.68 (95% CI 1.11-2.55), results at follow-up RR 2.43 (95% CI 1.61-3.66), and compliance RR 0.48 (95% CI 0.38-0.59). In respect of the use of heroin during the treatment, the differences were not statistically significant but favoured the combined treatments., Reviewers' Conclusions: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, results at follow-up and compliance. Although a treatment, like detoxification, that exclusively attenuates the severity of opiate withdrawal symptoms can be at best partially effective for a chronic relapsing disorder like opiate dependence, this type of treatment is an essential step prior to longer-term drug-free treatment and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective. Limitations to this review are imposed by the heterogeneity of the assessment of outcomes. Because of lack of detailed information no meta analysis could be performed to analyse the results related to several outcomes.

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: Methadone maintenance at proper doses is effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of the psychosocial services that are offered by most maintenance programs., Objectives: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus any agonist treatment alone in retaining patients in treatment, reducing the use of substances and improving health and social status., Search Strategy: We searched the Cochrane Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of relevant articles. There were no language or publication restrictions., Selection Criteria: RCTs which focus on any psychosocial plus any agonist compared to any agonist maintenance intervention for opiate dependence. People aged less than 18 and pregnant women were excluded. Psychosocial in combination with antagonist maintenance treatment are excluded too., Data Collection and Analysis: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked., Main Results: The searching process resulted in the identification of 77 different studies: 12 studies met the inclusion criteria. These studies considered 8 different psychosocial interventions and 1 pharmacological treatment: Methadone Maintenance (MMT). The results show additional benefit in adding any psychosocial treatment to standard methadone maintenance treatment in relation to the use of heroin during the treatment RR 0.69 (95% CI 0.53-0.91); no statistically significant additional benefit was shown in terms of retention in treatment RR 0.94 (95% CI 0.85-1.02); and results at follow-up RR 0.90 (95% CI 0.76-1.07)., Reviewers' Conclusions: The present evidence suggests that adding any psychosocial support to Standard MMT significantly improves the non-use of heroin during treatment. Retention in treatment and results at follow-up are also improved, although this findings did not achieve statistical significance. Insufficient evidence is available on other possible relevant outcomes such as Psychiatric symptoms/psychological distress, Quality of life. Limitations to this review are imposed by the heterogeneity of the trials both in the interventions and the assessment of outcomes. Results of studies were sometimes in disagreement and because of lack of detailed information no meta analysis could be performed to analyse the results related to the outcomes more often reported as positive results in the single studies. Duration of the studies was also too short to analyse other relevant outcomes such as mortality. In order to study the possible added value of any psychosocial treatment over an already effective treatment such as standard MMT, only big multi-site studies could be considered which define experimental interventions and outcomes in the most standardized way as possible.

Aim: To provide an overview of 5 Cochrane reviews of different approaches for treating opioid withdrawal., Design: Narrative and quantitative summary of review findings., Participants: There were 46 studies included in the original reviews with a total of 3350 participants (range 18-300)., Intervention: The 5 reviews considered 46 studies covering seven different comparisons, the major ones being methadone compared with alpha2-adrenergic agonists and other opioid agonists, different alpha2-adrenergic agonists compared with each other and to antagonist-induced withdrawal and buprenorphine., Measurements: The outcomes considered were signs and symptoms of withdrawal, retention in treatment, completion rate, relapse rate and side effects., Findings: Methadone detoxification results in higher retention in treatment, lower relapse rate and fewer side effects when compared with adrenergic agonists. No difference was observed when comparing different adrenergic agonists; buprenorphine appears to have an advantage over adrenergic agonists on withdrawal symptoms and side effects., Conclusions: Despite the considerable number of trials that have been carried out on this topic, they are very heterogeneous as far as the comparisons and outcomes considered. This prevented many of them from being incorporated into a quantitative meta-analysis. Consensus in measurements and results should be reached among researchers involved in the evaluation of the effectiveness of treatments for opiate addiction in order to produce consistent outcomes in the measuring and reporting of results from clinical trials.

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: Despite widespread use of naltrexone maintenance in many countries for more than a decade, the evidence of its effects has not yet been systematically evaluated., Objectives: To evaluate the effects of naltrexone maintenance treatment in preventing relapse in opioid addicts after detoxification., Search Strategy: We searched MEDLINE (1973-first year of naltrexone use in humans-July 2000), EMBASE (1974-July 2000), Cochrane Controlled Trials Register (Cochrane Library issue 2001.4) and handsearched the "Bolletino per le Farmacodipendenze e l'Alcolismo" (1978 to 1997) and reference lists of relevant articles. We contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups. Date of most recent searches: February 2003., Selection Criteria: All controlled studies of naltrexone; treatment of heroin addicts after detoxification., Data Collection and Analysis: Reviewers evaluated data independently and analysed outcome measures taking into consideration adherence to and success of the study intervention. Data were extracted and analysed stratifying for the three categories of study quality. Where possible, meta-analysis was performed., Main Results: Eleven studies met the criteria for inclusion in this review, even if not all of them were randomised. The methodological quality of the included studies varied, but was generally poor. Meta-analysis could be performed to a very low degree only, because the studies and their outcome measures were very heterogeneous. A statistically significant reduction of (re-)incarcerations was found for patients treated with naltrexone and behaviour therapy in respect to those treated with behaviour therapy only. The other outcomes considered in the meta-analysis did not yield any significant results. Final conclusions on whether naltrexone treatment may be considered effective in maintenance therapy cannot be drawn from the clinical trials available so far., Reviewer's Conclusions: The available trials do not allow a final evaluation of naltrexone maintenance treatment yet. A trend in favour of treatment with naltrexone was observed for certain target groups (particularly people who are highly motivated), as has been previously described in the literature.

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 naltrexone maintenance in many countries for more than a decade, the evidence of its effects has not yet been systematically evaluated., Objectives: To evaluate the effects of naltrexone maintenance treatment in preventing relapse in opioid addicts after detoxification., Search Strategy: We searched MEDLINE (1973-first year of naltrexone use in humans-July 2000), EMBASE (1974-July 2000), Cochrane Controlled Trials Register (Cochrane Library issue 2001.4) and handsearched the "Bolletino per le Farmacodipendenze e l'Alcolismo" (1978 to 1997) and reference lists of relevant articles. We contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups. Date of most recent searches: December 2001., Selection Criteria: All controlled studies of naltrexone; treatment of heroin addicts after detoxification., Data Collection and Analysis: Reviewers evaluated data independently and analysed outcome measures taking into consideration adherence to and success of the study intervention. Data were extracted and analysed stratifying for the three categories of study quality. Where possible, meta-analysis was performed., Main Results: Eleven studies met the criteria for inclusion in this review, even if not all of them were randomised. The methodological quality of the included studies varied, but was generally poor. Meta-analysis could be performed to a very low degree only, because the studies and their outcome measures were very heterogeneous. A statistically significant reduction of (re-)incarcerations was found for patients treated with naltrexone and behaviour therapy in respect to those treated with behaviour therapy only. The other outcomes considered in the meta-analysis did not yield any significant results. Final conclusions on whether naltrexone treatment may be considered effective in maintenance therapy cannot be drawn from the clinical trials available so far., Reviewer's Conclusions: The available trials do not allow a final evaluation of naltrexone maintenance treatment yet. A trend in favour of treatment with naltrexone was observed for certain target groups (particularly people who are highly motivated), as has been previously described in the literature.