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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.)

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: Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality., Methods: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for 10,208 person-years in treatment and 2,914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment., Results: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8-5.4] and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period., Conclusions: We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use.

Aim: To evaluate the efficacy of naltrexone maintenance treatment in preventing relapse in opioid addicts after detoxification., Design: A systematic review according to the methodology developed by the Cochrane Collaboration based on either randomized controlled trials (RCTs) or controlled clinical trials (CCTs)., Participants: Seven hundred and seven heroin dependent in- and out-patients, or former heroin addicts dependent on methadone and participating in a naltrexone treatment programme; 89% were male., Intervention: Maintenance treatments on opiate dependent people after detoxification, comparing naltrexone with placebo, pharmacological or behavioural treatments., Measurements: The outcomes considered were successfully completed treatment, opioid use under treatment (re)-incarcerations during the study period, mean duration of treatment., Findings: The outcomes tended to be slightly although not significantly in favour of the naltrexone groups. Use of naltrexone in addition to behavioural treatment significantly decreased the probability of (re-)incarceration (OR=0.30; 95% CI 0.12, 0.76). The difficulties in producing a quantitative analysis were due mainly to the heterogeneity of the included studies., Conclusions: From the available clinical trials performed up to this time, there is insufficient evidence to justify the use of naltrexone in maintenance treatment of opioid addicts.

Aim: To analyse overall and cause-specific mortality among problem drug users (PDUs) attending treatment centres in Rome and to evaluate differences in mortality between genders., Methods: A cohort of 11 432 PDUs entering treatment in Rome between 1980 and 1995 was enrolled and followed-up as of May 31, 1997. Directly standardized mortality rates and standardized mortality ratios (SMRs) and their 95% confidence intervals (95% CI) were calculated., Results: The study population included mainly males (82%), heroin users (92%) and had a mean age of 26.6 (SD 5.9) at enrollment. At the end of the study period 1734 deaths were observed. Overall mortality rates began to increase in 1985-86 and decreased slightly afterwards. AIDS mortality peaked in 1991-92 (13.2/1000) and fell in the following years. A slight decrease in overdose mortality also occurred after 1989-90. Mortality for causes other than AIDS and overdose remained high and relatively steady for the whole study period. Women showed higher mortality rates for AIDS but lower mortality rates for overdose than males. Overall mortality risk among drug addicts was about 15 times higher compared to the general population of the same age among men, and 38 times higher among women., Conclusions: AIDS mortality among drug addicts began to decrease earlier than expected; the decrease was particularly significant in the period 1993-94 for both sexes. Afterwards a continuous but slight decrease was observed among males only. Even though overdose mortality has also decreased slightly in recent years, we still observe high mortality levels for both overdose and all other causes. These findings suggest that interventions directed specifically towards the reduction of baseline mortality are still needed.