The suitability of oral diacetylmorphine in treatment-refractory patients with heroin dependence: A scoping review.

OBJECTIVE: To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. METHODS: The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria. RESULTS: Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest 'rush' after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients. CONCLUSIONS: Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial 'rush'. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.

Fifteen years of heroin-assisted treatment in a Swiss prison-a retrospective cohort study.

BACKGROUND: In the context of the current US opioid crisis and the compelling fact that a quarter to a third of all those addicted to heroin pass through its prisons and jails each year, the care of incarcerated opioid-using individuals (OUI) needs to be improved. AIMS: Little has been published on the effectiveness or outcomes of heroin-assisted treatment (HAT), a treatment option for severely dependent OUI delivered in a prison setting. The aim of this study was therefore to evaluate such treatment since its implementation. The primary objective was to investigate whether heroin-assisted treatment was associated with severe detrimental health outcomes. The secondary objective was to compare the heroin-assisted treatment group with the general prison population in terms of occupational functioning. DESIGN: Retrospective cohort study SETTING: An open prison with 120 places SUBJECTS: Data on 1885 male prisoners with a total of 2239 imprisonment periods between 2000 and 2015 was available. Ninety-seven inmates in heroin-assisted treatment were compared with 1788 inmates from the general prison population (reference group). MEASUREMENTS: Mortality, medical complications (including overdoses), and work performance (days worked, sick days, and monthly wages earned). FINDINGS: Inmates receiving HAT were on average 1 year younger (33.8 vs. 34.9 years), had longer prison stays (7.3 vs. 3.0 months), were more often of Swiss nationality (68.0% vs. 28.9%), and had committed more drug- and property-related offenses (49.5% vs. 23.2% and 63.9% vs. 38.3%, respectively) compared to the reference group. No serious heroin-related medical complication occurred during the 15-year window of observation among inmates with heroin-assisted treatment. Their work performance was comparable to that of the reference group. CONCLUSIONS: This study shows that heroin-assisted treatment can be a valuable treatment option for severely dependent OUI during imprisonment, can be delivered safely by prison health staff over extended periods of time, and allows OUI in treatment to achieve work performance rates comparable to that of the general prison population.

Rates of HIV and Hepatitis Infections in Clients Entering Heroin-Assisted Treatment between 2003 and 2013 and Risk Factors for Hepatitis C Infection.

BACKGROUND/AIMS: We report on the rates of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in 1,313 clients entering heroin-assisted treatment (HAT) in Switzerland from 2003 to 2013. We identify predictors of HCV infection. METHODS: Data were collected using questionnaires within 2 weeks of clients' first entry into HAT. Prevalence of HAV, HBV, HCV and HIV was calculated using laboratory test results collected at entry or using reports of older test results. Predictors of HCV status were identified through multiple logistic regression analysis. RESULTS: Results show stable rates of HIV-positive clients and decreasing proportions of HAV- and HBV-infected clients. In 2013, there were 12% (n = 8) HIV-, 20% (n = 12) HAV-, 20% (n = 12) HBV- and 52% HCV- (n = 34) positive clients. Vaccination against HAV and HBV had become more frequent. Predictors of positive HCV status included older age, female gender, earlier year of entry, having spent 1 month or more in detention or prison, use of injected heroin and more years of intravenous use. CONCLUSION: Our results highlight the fact that efforts to prevent and test for infections and to promote vaccination against HAV and HBV in heroin users need to be continued.

Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction†.

BACKGROUND: Supervised injectable heroin (SIH) treatment has emerged over the past 15 years as an intensive treatment for entrenched heroin users who have not responded to standard treatments such as oral methadone maintenance treatment (MMT) or residential rehabilitation. AIMS: To synthesise published findings for treatment with SIH for refractory heroin-dependence through systematic review and meta-analysis, and to examine the political and scientific response to these findings. METHOD: Randomised controlled trials (RCTs) of SIH treatment were identified through database searching, and random effects pooled efficacy was estimated for SIH treatment. Methodological quality was assessed according to criteria set out by the Cochrane Collaboration. RESULTS: Six RCTs met the inclusion criteria for analysis. Across the trials, SIH treatment improved treatment outcome, i.e. greater reduction in the use of illicit 'street' heroin in patients receiving SIH treatment compared with control groups (most often receiving MMT). CONCLUSIONS: SIH is found to be an effective way of treating heroin dependence refractory to standard treatment. SIH may be less safe than MMT and therefore requires more clinical attention to manage greater safety issues. This intensive intervention is for a patient population previously considered unresponsive to treatment. Inclusion of this low-volume, high-intensity treatment can now improve the impact of comprehensive healthcare provision.

Understanding Swiss drug policy change and the introduction of heroin maintenance treatment.

AIMS: The aim of this paper is to illustrate how Switzerland was able to play such a pioneering role in the field of addiction treatment, in creating a drug policy that includes the medical prescription of diacetylmorphine (heroin). The paper will also describe the role of knowledge brokering processes and coalition building in the different phases of the development of the Swiss drug policy. DISCUSSION: The medical prescription of diacetylmorphine was the exotic element of the Swiss drug policy of 1991 and probably still is one of the most controversial practices in clinical medicine despite its documented effectiveness. Coalitions of change actors, across stakeholder groups from many professions and politicians on various levels, succeeded in formulating and starting initiatives for a new drug policy and its innovations. Clear, shared objectives and a common feeling of urgency brought the coalitions together. CONCLUSION: In the case of Switzerland, the Confederation took a leading role by facilitating communication, encouraging scientific knowledge and bringing the various stakeholders on a platform to deliver a consensual political policymaking basis. This was facilitated by the Swiss direct democracy system. Sustained dialogue between researchers and the users of research enhances the likelihood of research affecting policy.

Building a European consensus on minimum quality standards for drug treatment, rehabilitation and harm reduction.

BACKGROUND/AIMS: The Study on the Development of an EU Framework for Minimum Quality Standards and Benchmarks in Drug Demand Reduction (EQUS) has set up an inventory of quality standards and initiated a consensus-building process, aiming at establishing a set of European minimum quality standards (MQS) for treatment/rehabilitation and harm reduction in the field of drug abuse and dependence. METHODS: Existing documents were collected by country-specific experts and integrated into a predefined framework of quality standards. Agreement, implementation status and expected implementation problems of the proposed standards were assessed by a survey of European stakeholders and the final lists of European MQS were established at a European conference. RESULTS: Overall, 349 documents were identified as relevant. Major gaps were identified for ethical and legal standards, and for documents that provide grades of evidence for specific standards. A high level of acceptance was found for the treatment/rehabilitation MQS, while a somewhat lower level was found for the harm reduction MQS. The final lists of MQS were based on at least 80% of acceptance by European experts and stakeholders. CONCLUSION: A high consensus of European MQS for treatment/rehabilitation and harm reduction has been achieved. Further implementation and developmental steps are discussed.

La importancia de las coaliciones en las políticas sobre drogas. Algunas consideraciones derivadas de la teoría y de la observación / The role of coalitions in drug policy. Some theoretical and observational considerations

Las sociedades organizadas democráticamente están obligadas a encontrar la manera de proceder en caso de necesitar una reformulación de las estrategias frente a los nuevos avances sociales y tecnológicos, especialmente cuando hay preferencias e intereses controvertidos. Los cambios en política de drogas son un ejemplo excelente para discutir el problema y el proceso de formación de coaliciones para encontrar respuestas aceptables a los nuevos desafíos. La moderna teoría sociológica ha desarrollado conceptos y herramientas para la descripción y el análisis de tales procesos. El estudio de casos concretos referentes a ciudades suizas pueden servirnos para la discusión avanzada de conceptos teóricos. El seguimiento observacional de la formación de coaliciones en la ciudad de Zurich, ayuda a ilustrar los elementos inherentes, los problemas, y los resultados. Un análisis más detallado del proceso centrado en las fases iniciales y el desarrollo subsiguiente de diversas coaliciones formales e informales introduce la importancia de los objetivos compartidos y la necesidad de actividades concertadas. No se dispuso al principio de un concepto de política clara y un plan de acción coherente, pero resultó ser un paso importante en la consolidación de lo que fue un comienzo no sistematizado. Lo que se inició a nivel local y llego a ser una nueva política nacional, dejo de ser un enfrentamiento constante entre dos ideologías – la reducción de daños contra la prohibición estricta -, para convertirse en el comienzo de una nueva forma de pensar acerca de cómo los elementos de las diferentes estrategias podrían combinarse con éxito en la búsqueda de un objetivo concreto a compartir. Estas observaciones pueden ser consideradas en futuros desarrollos teóricos y consideración sobre políticas (AU)

Democratically organised societies have to find ways how to proceed when in need of a reformulation of strategies in face of new societal and technological developments, especially in dealing with controversial preferences and interests. The area of drug policy change presents an excellent example for discussing the problem and the process of coalition building for finding acceptable answers to new challenges. Modern sociological theory has developed concepts and tools for a description and analysis of such processes. Some concrete case studies from Swiss cities are available as a basis for advanced discussion of theoretical concepts. The observational description of the coalition building in the city of Zurich helps to illustrate the inherent elements, problems and outcomes; a more detailed process analysis focuses on the initial phases and further development of the various formal and informal coalitions, introducing the importance of shared objectives for action and the need for concerted activities. A clear policy concept and a consistent action plan were not available at first, but they proved to be an important step in the consolidation of what was a non-systematic beginning. What started at local level and led to a new national policy was not so much a continued clash between two ideologies – harm reduction versus strict prohibition -, but was the beginning of a new thinking about how the various policy elements could successfully work together in the pursuit of a shared concrete objective. These observations may be considered in further theory development and policy considerations (AU)

The role of coalitions in drug policy. Some theoretical and observational considerations.

Democratically organised societies have to find ways how to proceed when in need of a reformulation of strategies in face of new societal and technological developments, especially in dealing with controversial preferences and interests. The area of drug policy change presents an excellent example for discussing the problem and the process of coalition building for finding acceptable answers to new challenges. Modern sociological theory has developed concepts and tools for a description and analysis of such processes. Some concrete case studies from Swiss cities are available as a basis for advanced discussion of theoretical concepts. The observational description of the coalition building in the city of Zurich helps to illustrate the inherent elements, problems and outcomes; a more detailed process analysis focuses on the initial phases and further development of the various formal and informal coalitions, introducing the importance of shared objectives for action and the need for concerted activities. A clear policy concept and a consistent action plan were not available at first, but they proved to be an important step in the consolidation of what was a non-systematic beginning. What started at local level and led to a new national policy was not so much a continued clash between two ideologies - harm reduction versus strict prohibition -, but was the beginning of a new thinking about how the various policy elements could successfully work together in the pursuit of a shared concrete objective. These observations may be considered in further theory development and policy considerations.

Heroin maintenance treatment: from idea to research to practice.

Maintaining opiate addicts on opiates has a long history. The idea to prescribe pharmaceutical morphine as a substitute for street heroin started in USA and was abolished on the basis of prohibitionist legislation. A new approach to maintain opiate addicts on substitution therapy was initiated in USA in 1963, with the prescription of methadone. This approach found, although slowly, increasing acceptance, and is nowadays considered to be a cornerstone in the management of opiate dependence and for the prevention of HIV/AIDS in opiate injectors. Since 1975, the concept of heroin maintenance treatment was re-activated in order to reach out to treatment-resistant heroin addicts. Research projects were performed in Switzerland, the Netherlands, Germany, Spain, Canada and in England, another one is planned in Belgium. Based on the unanimously positive outcomes, heroin maintenance has become routine treatment for otherwise untreatable heroin addicts in Switzerland, the Netherlands, Germany and England, and Denmark has set up heroin maintenance without new research trials.

Predictors of retention in the 'voluntary' and 'quasi-compulsory' treatment of substance dependence in europe.

BACKGROUND: Policies and practices related to the quasi-compulsory treatment (QCT) of substance-dependent offenders are currently implemented in many countries, despite the absence of reliable knowledge about significant predictors of treatment retention. This study aimed to identify such predictors in QCT and voluntary treatment. METHODS: Participants were treated in one of 65 institutions in 5 European countries. They were interviewed at intake on substance use, crimes committed, perceived pressure for treatment, self-efficacy, stage of change, employment, and health-related variables. Binary logistic regression models were computed to identify predictors of treatment retention at an 18-month follow-up. Moderator analyses were computed to investigate whether these predictors vary by treatment condition (QCT vs. voluntary). RESULTS: A higher number of working days in the previous month was positively associated with treatment retention, while use of heroin, crack, and multiple drugs, psychiatric problems in the previous month, and lifetime depression were negatively associated with treatment retention. Higher perceived medical pressure resulted in higher treatment retention rates only for participants in QCT. CONCLUSION: Predictors of substance abuse treatment retention are quite similar across both QCT and voluntary treatments. Perceived medical pressure is of higher relevance than the often-believed legal pressure for treatment retention in QCT.

Ethical perspectives in caring for people living with addictions: The European experience.

European policy and practice in caring for people living with addictions is based on defined values (human rights, medical ethics) and on research evidence for the effects and impact of interventions. The focus of the paper is on risk management approaches to reduce the negative consequences of continued illicit drug use, being the ethically most debatable issue. The legal and policy positions are set by the European Council and Commission, and their translation into practice is documented centrally in the European Monitoring Centre on Drugs and Drug Addiction, showing the general trends as well as national differences. The European experience with the risk management approaches is presented in terms of research evidence on their effects and side-effects; this evidence is justifying the present practice. The perspectives for the future are set to follow the same lines, in a continued effort to find a balance of interests, in cooperation of authorities and civil society, and guided by ongoing research.

Long-term follow-up of orally administered diacetylmorphine substitution treatment.

BACKGROUND: To assess the long-term course of the feasibility and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users. DESIGN: Open-label, prospective cohort study with 2 non-randomly assigned treatment arms: DAM tablets only (n = 128) or DAM tablets combined with injected DAM and/or other opioids (n = 237). The average duration of the observation period was 62 months. Study endpoints were the time to discharge from treatment and the number of serious adverse events. RESULTS: Both patient groups had a higher than 70% retention rate after the first 48 months of treatment, with similar long-term retention rates (after 8 years both groups had retention over 50%). The physician-verified rate of serious adverse events was 0.01 events per application year among the exclusively oral substitution group (intention-to-treat analysis) during the last year of observation, and 0.005 events per application year in the other group. CONCLUSIONS: Because of their feasibility and safety over years, DAM tablets may be a valuable long-term therapeutic alternative.

[Prognostic factors from a long-term follow-up of heroin-assisted treatment in Switzerland 1994-2007]. / Heroingestützte Behandlung in der Schweiz im Langzeitverlauf 1994-2007: Einflussfaktoren auf den Behandlungserfolg.

OBJECTIVE: To identify prognostic factors for a positive or negative termination of heroin-assisted treatment (HAT) in Switzerland. METHOD: A complete census of all 3155 patients ever admitted was analysed using the proportional hazard model (including time dependent covariates). RESULTS: Median length of stay was 11.4 years; the maximal length of stay was 13.9 years. 299 positive and 463 negative terminations were registered. Terminations clustered in the first year. Both time to positive and negative termination was significantly dependent on historical treatment cohorts since 1994. Positive termination was negatively associated with treatment in larger treatment centres (OR: 0.77, CI: 0.61-0.97) and positively with income from the social system (OR: 1.33; CI: 1.03-1.72). Negative terminations were positively associated with HIV infection before treatment (OR: 1.74; CI: 1.40-2.16), delinquence (OR 1.36; CI: 1.09-1.69), and higher levels of distrust (OR: 1.18 per scoring point; CI = 1.05-1.31). CONCLUSIONS: Length of stay in Swiss HAT is considerable. The proportion of positive terminations did not increase with longer stays, indicating that the majority of patients are in chronic palliative care. Negative terminations outweighed positive terminations, with a low predictive power from co-variates. The routine assessment and analysis of different covariates, such as indicators of treatment process, has the potential to improve the therapeutic outcomes of HAT.

Heroin-assisted treatment in Switzerland: a case study in policy change.

BACKGROUND: Switzerland introduced a pragmatic national drug policy when the former conservative abstinence-orientated politics proved unable to cope with an escalating number of users and related negative consequences for public health and public order. The high visibility of 'needle parks' and the size of the acquired immune deficiency disorder (AIDS) epidemic called for a new approach and for national leadership. AIMS: To describe the intentions, the process and the results of setting up the new treatment approach of prescribing heroin to treatment resistant heroin addicts, as an example of drug policy change. MATERIALS AND METHODS: A systematic collection of relevant documents is analysed and used as evidence for describing the process of policy change. RESULTS: Measures to reduce the negative consequences of continued use and to prevent the spread of AIDS were started mainly by private initiatives and soon taken up officially in the 'four-pillar' drug policy (including harm reduction, prevention, treatment and law enforcement). Medical prescription of heroin to chronic, treatment-resistant heroin addicts was one of the innovations, based on extensive scientific and political preparation. Detailed documentation and evaluation, ample communication of results, adaptations made on the basis of results and extensive public debate helped to consolidate the new policy and heroin-assisted treatment, in spite of its limitations as an observational cohort study. All necessary steps were taken to proceed from a scientific experiment to a routine procedure. DISCUSSION: Comparable policy changes have been observed in a few other countries, such as The Netherlands and Germany, based on the Swiss experience, with equally positive results of heroin-assisted treatment. These experiments were designed as randomised controlled trials, comparing intravenous heroin against oral methadone, thereby demonstrating the specific value of pharmaceutical diamorphine for maintenance treatment in opiate dependence. The positive impact of policy change and the positive outcomes of heroin-assisted treatment were acknowledged increasingly nationally and internationally, but made it difficult to continue the process of adapting policy to new challenges, due to the low visibility of present drug problems and to changing political priorities. CONCLUSION: A major change in drug policy was effectively realised under typical conditions of a federalist country with a longstanding tradition of democratic consensus building. Facilitating factors were the size and visibility of the heroin problem, the rise of the Aids epidemic, and a pragmatic attitude of tolerating private initiatives opening the way to official policy change.