Predictors of effective therapy among individuals with Cannabis Use Disorder: a review of the literature.

Treatment demand for Cannabis Use Disorder (CUD) has increased in the past decade in almost all European countries, and CUD is currently the most common reason for first-time drug-related treatment admission in the European Union. Even though several therapeutic approaches have been shown to benefit individuals with CUD, there is a lack of knowledge regarding factors associated with effective therapy and the underlying mechanisms of change among individuals with CUD presenting for treatment. The aim of the present paper was to review current knowledge on factors that have been shown to contribute to positive outcomes in CUD treatment. A scoping methodology was used, focusing on empirically evaluated studies that used defined, cannabis-related outcome measures. In eligible studies, factors of investigation were categorized as either 'mediators', i.e., treatment-related factors associated with the processes or mechanisms through which patients benefit from therapy, or 'moderators' which are patient-related characteristics that predict his/her odds to benefit from treatment or patient-related (i.e., moderators). Factors categorized as mediators were then classified 'specific factors' if they were related to a certain technique or treatment modality or 'common factors' if they were assessed beyond treatment modalities. Findings suggest that in CUD treatment, specific mediators include treatment duration, addressing motivation to change, acquiring coping skills, enhancing self-efficacy, and integrating several therapeutic components. Common mediators include therapeutic alliance, empathy, expectations and cultural adaptation. Moderators in CUD treatment include sex, ethnicity, age-related factors and comorbid disorders.

Effectiveness of psychosocial interventions for alcohol use disorder: a systematic review and meta-analysis update.

Background: Given the accumulating research, evolving psychosocial treatment, and equivocal findings, updating WHO's Mental Health Gap Action Programme-2015 was necessary to ensure guidelines reflect effective strategies for alcohol use disorder (AUD).Objective: To estimate the effects of psychosocial interventions on drinking and related outcomes.Methods: We included randomized controlled trials published between January 2015 and June 2022 on adults with alcohol dependence (ICD 10/DSM-IV) and moderate to severe AUD (DSM-5), and those examined psychosocial interventions against treatment-as-usual (TAU) and active controls. Eight databases and registries were searched. Relative Risk (RR) and standardized mean difference (SMD) were used for dichotomous and continuous outcomes. We used Cochrane's risk of bias assessment (RoB2).Results: Of 873 screened records, 14 and 13 studies in the narrative synthesis and meta-analysis. Of the 2,575 participants, 71.5% were men. Thirteen studies used ICD 10/DSM IV diagnosis. Compared to TAU, any psychosocial intervention increased the relative risk of abstinence by 28% [N = 7, RR = 1.28, 95% CI: 1.07 to 1.53, p = .01, NNT = 9]. There were minimal heterogeneity and no evidence of publication bias. Psychosocial interventions were not effective in reducing the drinking frequency (n = 2, Hedge's g = -0.10, 95% CI: -0.46 to 0.26, p = .57) and drinks/drinking days (N = 5, g = -0.10, 95% CI: -0.37 to 0.16, p = .43). Treatment discontinuation did not differ between intervention and control groups [RR = 1.09, 95% CI: 0.66 to 1.80].Conclusion: Psychosocial interventions are effective in improving abstinence but not in reducing drinking frequency or amount. Policymakers must consider this evidence to generate AUD treatment guidelines.Registration: PROSPERO 2022 CRD42022342608.

Univariable associations between a history of incarceration and HIV and HCV prevalence among people who inject drugs across 17 countries in Europe 2006 to 2020 - is the precautionary principle applicable?

BackgroundPeople who inject drugs (PWID) are frequently incarcerated, which is associated with multiple negative health outcomes.AimWe aimed to estimate the associations between a history of incarceration and prevalence of HIV and HCV infection among PWID in Europe.MethodsAggregate data from PWID recruited in drug services (excluding prison services) or elsewhere in the community were reported by 17 of 30 countries (16 per virus) collaborating in a European drug monitoring system (2006-2020; n = 52,368 HIV+/-; n = 47,268 HCV+/-). Country-specific odds ratios (OR) and prevalence ratios (PR) were calculated from country totals of HIV and HCV antibody status and self-reported life-time incarceration history, and pooled using meta-analyses. Country-specific and overall population attributable risk (PAR) were estimated using pooled PR.ResultsUnivariable HIV OR ranged between 0.73 and 6.37 (median: 2.1; pooled OR: 1.92; 95% CI: 1.52-2.42). Pooled PR was 1.66 (95% CI 1.38-1.98), giving a PAR of 25.8% (95% CI 16.7-34.0). Univariable anti-HCV OR ranged between 1.06 and 5.04 (median: 2.70; pooled OR: 2.51; 95% CI: 2.17-2.91). Pooled PR was 1.42 (95% CI: 1.28-1.58) and PAR 16.7% (95% CI: 11.8-21.7). Subgroup analyses showed differences in the OR for HCV by geographical region, with lower estimates in southern Europe.ConclusionIn univariable analysis, a history of incarceration was associated with positive HIV and HCV serostatus among PWID in Europe. Applying the precautionary principle would suggest finding alternatives to incarceration of PWID and strengthening health and social services in prison and after release ('throughcare').

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. OBJECTIVES: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. DATA COLLECTION AND ANALYSIS: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. MAIN RESULTS: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

Maintenance agonist treatments for opiate-dependent pregnant women.

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.

Alcoholics Anonymous and 12-Step Facilitation Treatments for Alcohol Use Disorder: A Distillation of a 2020 Cochrane Review for Clinicians and Policy Makers.

AIMS: A recently completed Cochrane review assessed the effectiveness and cost-benefits of Alcoholics Anonymous (AA) and clinically delivered 12-Step Facilitation (TSF) interventions for alcohol use disorder (AUD). This paper summarizes key findings and discusses implications for practice and policy. METHODS: Cochrane review methods were followed. Searches were conducted across all major databases (e.g. Cochrane Drugs and Alcohol Group Specialized Register, PubMed, Embase, PsycINFO and ClinicalTrials.gov) from inception to 2 August 2019 and included non-English language studies. Randomized controlled trials (RCTs) and quasi-experiments that compared AA/TSF with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants or no treatment, were included. Healthcare cost offset studies were also included. Studies were categorized by design (RCT/quasi-experimental; nonrandomized; economic), degree of manualization (all interventions manualized versus some/none) and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). Random-effects meta-analyses were used to pool effects where possible using standard mean differences (SMD) for continuous outcomes (e.g. percent days abstinent (PDA)) and the relative risk ratios (RRs) for dichotomous. RESULTS: A total of 27 studies (21 RCTs/quasi-experiments, 5 nonrandomized and 1 purely economic study) containing 10,565 participants were included. AA/TSF interventions performed at least as well as established active comparison treatments (e.g. CBT) on all outcomes except for abstinence where it often outperformed other treatments. AA/TSF also demonstrated higher health care cost savings than other AUD treatments. CONCLUSIONS: AA/TSF interventions produce similar benefits to other treatments on all drinking-related outcomes except for continuous abstinence and remission, where AA/TSF is superior. AA/TSF also reduces healthcare costs. Clinically implementing one of these proven manualized AA/TSF interventions is likely to enhance outcomes for individuals with AUD while producing health economic benefits.

Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions.

Substance use prevention: evidence-based intervention.

The global substance use problem is a serious public health concern that affects not only health, safety and well-being of communities, but also social and economic development. It particularly affects children, young people and their families. All Member States should set substance use prevention measures and programmes as a priority in order to promote health and reduce social harm. During the past few decades there has been a significant advance in prevention science that has led to the development of international prevention standards and globally accepted evidence-based interventions. This review looks into the key requirements, components and strategic interventions needed for a public health approach to prevention of substance use and disorders, and its health and social consequences. It aims at supporting Member States and civil society to identify the key elements that support countries and local communities to increase the number of substance use protective approaches in relation to risk factors across all relevant domains.

Digital Interventions for Problematic Cannabis Users in Non-Clinical Settings: Findings from a Systematic Review and Meta-Analysis.

BACKGROUND: Existing cannabis treatment programs reach only a very limited proportion of people with cannabis-related problems. The aim of this systematic review and meta-analysis was to assess the effectiveness of digital interventions applied outside the health care system in reducing problematic cannabis use. METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (2015), PubMed (2009-2015), Medline (2009-2015), Google Scholar (2015) and article reference lists for potentially eligible studies. Randomized controlled trials examining the effects of internet- or computer-based interventions were assessed. Study effects were estimated by calculating effect sizes (ESs) using Cohen's d and Hedges' g bias-corrected ES. The primary outcome assessed was self-reported cannabis use, measured by a questionnaire. RESULTS: Fifty-two studies were identified. Four studies (including 1,928 participants) met inclusion criteria. They combined brief motivational interventions and cognitive behavioral therapy delivered online. All studies were of good quality. The pooled mean difference (x0394; = 4.07) and overall ES (0.11) give evidence of small effects at 3-month follow-up in favor of digital interventions. CONCLUSIONS: Digital interventions can help to successfully reduce problematic cannabis use outside clinical settings. They have some potential to overcome treatment barriers and increase accessibility for at-risk cannabis users.

An International, Multidisciplinary Consensus Set of Patient-Centered Outcome Measures for Substance-Related and Addictive Disorders.

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience (n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

World addiction medicine reports: formation of the International Society of Addiction Medicine Global Expert Network (ISAM-GEN) and its global surveys.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Slow-release oral morphine as maintenance therapy for opioid dependence.

BACKGROUND: Opioid substitution treatments are effective in retaining people in treatment and suppressing heroin use. An open question remains whether slow-release oral morphine (SROM) could represent a possible alternative for opioid-dependent people who respond poorly to other available maintenance treatments. OBJECTIVES: To evaluate the efficacy of SROM as an alternative maintenance pharmacotherapy for the treatment of opioid dependence. SEARCH METHODS: We searched Cochrane Drugs and Alcohol Group's Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 3, 2013), MEDLINE (January 1966 to April 2013), EMBASE (January 1980 to April 2013) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials assessing efficacy of SROM compared with other maintenance treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles for inclusion, extracted data and assessed risk of bias of included studies. MAIN RESULTS: Three studies with 195 participants were included in the review. Two were cross-over trials and one was a parallel group RCT. The retention in treatment appeared superior to 80% in all the three studies (without significant difference with controls). Nevertheless, it has to be underlined that the studies had different durations. One lasted six months, and the other two lasted six and seven weeks. The use of opioids during SROM provision varied from lower to non-statistically or clinically different from comparison interventions, whereas there were no differences as far as the use of other substances was concerned.SROM seemed to be equal to comparison interventions for severity of dependence, or mental health/social functioning, but there was a trend for less severe opiate withdrawal symptoms in comparison with methadone (withdrawal score 2.2 vs. 4.8, P value = 0.06). Morphine was generally well tolerated and was preferred by a proportion of participants (seven of nine people in one study). Morphine appeared to reduce cravings, depressive symptoms (measured using the Beck Depression Inventory; P value < 0.001), physical complaints (measured using the Beschwerde-Liste (BL); P value < 0.001) and anxiety symptoms (P value = 0.008). Quality of life in people treated with SROM resulted in no significant difference or a worst outcome than in those taking methadone and buprenorphine. Other social functioning measures, such as finances, family and overall satisfaction, scored better in people maintained with the comparison substances than in those maintained with SROM. In particular, people taking methadone showed more favourable values for leisure time (5.4 vs. 3.7, P value < 0.001), housing (6.1 vs. 4.7, P value < 0.023), partnerships (5.7 vs. 4.2, P value = 0.034), friend and acquaintances (5.6 vs. 4.4, P value = 0.003), mental health (5.0 vs. 3.4, P value = 0.002) and self esteem (8.2 vs. 5.7, P value = 0.002) compared to people taking SROM; while people taking buprenorphine obtained better scores for physical health.Medical adverse events were consistently higher in people in SROM than in the comparison groups. None of the studies included people with a documented poor response to other maintenance treatment. AUTHORS' CONCLUSIONS: The present review did not identify sufficient evidence to assess the effectiveness of SROM for opioid maintenance because only three studies meeting our inclusion criteria have been identified. Two studies suggested a possible reduction of opioid use in people taking SROM. In another study, the use of SROM was associated with fewer depressive symptoms. Retention in treatment was not significantly different among compared interventions while the adverse effects were more frequent with the people given SROM.

Methadone at tapered doses for the management of opioid withdrawal.

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.

Media campaigns for the prevention of illicit drug use in young people.

BACKGROUND: Substance-specific mass media campaigns which address young people are widely used to prevent illicit drug use. They aim to reduce use and raise awareness of the problem. OBJECTIVES: To assess the effectiveness of mass media campaigns in preventing or reducing the use of or intention to use illicit drugs amongst young people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 1), including the Cochrane Drugs and Alcohol Group's Specialised Register; MEDLINE through PubMed (from 1966 to 29 January 2013); EMBASE (from 1974 to 30 January 2013) and ProQuest Dissertations & Theses A&I (from 1861 to 3 February 2013). SELECTION CRITERIA: Cluster-randomised controlled trials, prospective and retrospective cohort studies, interrupted time series and controlled before and after studies evaluating the effectiveness of mass media campaigns in influencing drug use, intention to use or the attitude of young people under the age of 26 towards illicit drugs. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of The Cochrane Collaboration. MAIN RESULTS: We included 23 studies involving 188,934 young people, conducted in the USA, Canada and Australia between 1991 and 2012. Twelve studies were randomised controlled trials (RCT), two were prospective cohort studies (PCS), one study was both a RCT and a PCS, six were interrupted time series and two were controlled before and after (CBA) studies. The RCTs had an overall low risk of bias, along with the ITS (apart from the dimension 'formal test of trend'), and the PCS had overall good quality, apart from the description of loss to follow-up by exposure.Self reported or biomarker-assessed illicit drug use was measured with an array of published and unpublished scales making comparisons difficult. Pooled results of five RCTs (N = 5470) show no effect of media campaign intervention (standardised mean difference (SMD) -0.02; 95% confidence interval (CI) -0.15 to 0.12).We also pooled five ITS studies (N = 26,405) focusing specifically on methamphetamine use. Out of four pooled estimates (two endpoints measured in two age groups), there was evidence of a reduction only in past-year prevalence of methamphetamine use among 12 to 17 years old.A further five studies (designs = one RCT with PCS, two PCS, two ITS, one CBA, N = 151,508), which could not be included in meta-analyses, reported a drug use outcome with varied results including a clear iatrogenic effect in one case and reduction of use in another. AUTHORS' CONCLUSIONS: Overall the available evidence does not allow conclusions about the effect of media campaigns on illicit drug use among young people. We conclude that further studies are needed.

Maintenance agonist treatments for opiate-dependent pregnant women.

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.

EMCDDA Best Practice Promotion in Europe: an internet based dissemination tool.

Best practice is the best application of available evidence to current activities in the drugs field. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) created a web-based tool aimed at bridging together scientific evidence and current practices in the drug addiction field. Beyond dissemination of evidence, the scope is to share best practice among the European countries. The synthesis of the evidence is based on the methods of the Cochrane collaboration (the Drugs and Alcohol Group) and the Grade working group. As of February 2013 the portal encompasses four modules on the effectiveness of demand reduction interventions, a collection of European projects on prevention, treatment, harm reduction and social reintegration and an inventory of European Guidelines and Standards including a bank of instruments to evaluate interventions (http://www.emcdda.europa.eu/bestpractice). The summaries of evidence are presented in a plain language format and include brief explanation of the measures of effect supporting the evidence, but do not provide specific recommendations. The main future challenge of EMCDDA's best practice promotion is to become a service for those willing to implement best practice. The Best Practice Portal should become a platform where to find all is needed for successful implementation (handbooks, training materials, guidelines for evaluation and contacts for mentoring).

Key implementation factors in telemedicine-delivered medications for opioid use disorder: a scoping review informed by normalisation process theory.

Telemedicine could improve access to medications for opioid use disorder (MOUD). Telemedicine-delivered MOUD (TMOUD) has expanded substantially in response to the restrictions imposed by the COVID-19 pandemic on in-person clinical contact, yet this expansion has not happened consistently across all health systems and countries. This Review aims to understand key factors in TMOUD implementation that might explain variations in uptake. We did a scoping review using three English language databases for articles reporting on the implementation of TMOUD services. 57 peer-reviewed articles were identified, subjected to open coding and thematic analysis, and further interpreted through normalisation process theory (NPT). NPT was originally used to evaluate telehealth innovations and has been applied extensively to describe, assess, and develop the implementation potential of a broad range of complex health-care interventions. By categorising our findings according to the four core NPT constructs of coherence, cognitive participation, collective action, and reflexive monitoring, we aim to rationalise the current evidence base to show the workability of TMOUD in practice. We find that variations in TMOUD models in practice depend on organisations' attitudes towards risk, clinicians' tensions around giving up control over standard practices, organisation-level support in overcoming operational and technological challenges, and evaluation methods that might neglect a potential widening of the digital divide.

Heroin maintenance for chronic heroin-dependent individuals.

BACKGROUND: Several types of medications have been used for stabilizing heroin users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The present review focuses on the prescription of heroin to heroin-dependent individuals. OBJECTIVES: To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding: efficacy and acceptability, retaining patients in treatment, reducing the use of illicit substances, and improving health and social functioning. SEARCH METHODS: A review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to november 2009), EMBASE (1980 to 2005) and CINAHL until 2005 (on OVID) was conducted. Personal communications with researchers in the field of heroin prescription identified ongoing trials. SELECTION CRITERIA: Randomised controlled trials of heroin maintenance treatment (alone or combined with methadone) compared with any other pharmacological treatment for heroin-dependent individuals. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Eight studies involving 2007 patients met the inclusion criteria. Five studies compared supervised injected heroin plus flexible dosages of methadone treatment to oral methadone only and showed that heroin helps patients to remain in treatment (valid data from 4 studies, N=1388 Risk Ratio 1.44 (95%CI 1.19-1.75) heterogeneity P=0.03), and to reduce use of illicit drugs. Maintenance with supervised injected heroin has a not statistically significant protective effect on mortality (4 studies, N=1477 Risk Ratio 0.65 (95% CI 0.25-1.69) heterogeneity P=0.89), but it exposes at a greater risk of adverse events related to study medication (3 studies N=373 Risk Ratio 13.50 (95% CI 2.55-71.53) heterogeneity P=0.52). Results on criminal activity and incarceration were not possible to be pooled but where the outcome were measured results of single studies do provide evidence that heroin provision can reduce criminal activity and incarceration/imprisonment. Social functioning improved in all the intervention groups with heroin groups having slightly better results. If all the studies comparing heroin provision in any conditions vs any other treatment are pooled the direction of effect remain in favour of heroin. AUTHORS' CONCLUSIONS: The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment refractory, opioid users, to reach a decrease in the use of illicit substances, involvement in criminal activity and incarceration, a possible reduction in mortaliity; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment for people who are currently or have in the past failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.

Heroin maintenance for chronic heroin-dependent individuals.

BACKGROUND: Several types of medications have been used for stabilizing heroin users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The present review focuses on the prescription of heroin to heroin-dependent individuals. OBJECTIVES: To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding: efficacy and acceptability, retaining patients in treatment, reducing the use of illicit substances, and improving health and social functioning. SEARCH STRATEGY: A review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to 2008), EMBASE (1980 to 2005) and CINAHL until 2005 (on OVID) was conducted. Personal communication with researchers in the field of heroin prescription identified other ongoing trials. SELECTION CRITERIA: Randomised controlled trials of heroin maintenance treatment (alone or combined with methadone) were compared with any other pharmacological treatment for heroin-dependent individuals. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Eight studies involving 2007 patients were included. Results show marginal significance in favour of heroin for remaining in treatment until the end of the study (8 studies, N= 2007, RR=1.23, 95%CI=0.96-1.57; heterogeneity P < 0.01). Adverse events are significantly more frequent in the heroin group. Heroin plus methadone prescription for maintenance treatment in adult chronic opioid users who failed previous methadone treatment attempts decreases the use of other illicit substances (3 Studies, N=1289, RR=0.63, 95%CI=0.49, 0.81, heterogeneity P=0.21), and reduces the risk of being incarcerated (2 studies, N=1103, RR=0.64, 95%CI=0.51-0.79, heterogeneity P=0.31). In addition, we also found a marginally significant protective effect of heroin prescription plus methadone for the use of street heroin (3 studies, N=1512, RR=0.70, 95%CI=0.49-1.00, heterogeneity P < 0.01) and for criminal activity (4 studies, N=1377, RR=0.80, 95%CI=0.61-1.04, heterogeneity P=0.31). There was not enough power to detect statistically significant results for the risk of death (5 studies, N=1817, RR=0.77, 95%CI=0.32-1.87, heterogeneity P=0.79). AUTHORS' CONCLUSIONS: The available evidence suggests a small added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment-refractory opioid users, considering a decrease in the use of street heroin and other illicit substances, and in the probability of being imprisoned; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment of last resort for people who are currently or have in the past failed maintenance treatment.