‘Heroin on Trial’: A summary of the conference
In the early 20th Century there were a few hundred people dependent on prescribed morphine and diamorphine (heroin was the original trade name of the drug) in the UK. Most had developed dependence on prescription medication, and many were members of the medical or nursing profession (it would not be until the 1970s that illicitly-manufactured imported street heroin would become readily available). Doctors in the UK had adopted a humane approach to this group, prescribing diamorphine to enable them to stay well and to function day-to-day. In contrast, with strict controls on psychoactive drugs imposed across the world as the First World War started, doctors in the USA were prevented from prescribing diamorphine to addicts. The UK approach was captured in the report of the Departmental Committee on Morphine and Heroin Addiction in 1926 (known as the Rolleston report) which maintained the view that addiction was a disease, and so a target for compassion and treatment (see Findings commentary)
This ‘British System’ (treating opiate addicts as patients rather than criminals, and legitimising the provision of substitute opiate treatment) is often credited with having kept drug dependence in check until the early 1960s, although this view has been disputed (see Strang & Gossop 2005 and Best, George & Day 2007). The number of opiate addicts in the UK had remained largely static and fairly small (usually no more than 600 at any time). However, the 1960s saw a change in the socio-cultural climate and an increase in heroin use by young people, and the problem was seen as getting out of hand. New policy recommendations were made and specialist drug clinics to treat addicts were established for the first time.
The first drug treatment clinics were set up in 1967, mainly in London and often attached to district general hospitals. They were headed by consultant psychiatrists and included multidisciplinary teams, for the comprehensive assessment and treatment of addicts. Prescribing of diamorphine was a mainstay of treatment, and speakers at the conference picked up the story of heroin-assisted treatment (HAT) from this point…
SESSION 1
Dr Martin Mitcheson, who led one of the influential clinics in the UK through the 1970s and 80s, began by describing his experiences in the 1970s, culminating in the first evaluation of diamorphine prescribing as a treatment approach LINK. He described a period of uncertainty and crisis within the British system and drug clinics, whereby the initial perceived aims started to be questioned. By the mid-1970s, it was apparent that the majority of outpatients attending clinics for a legitimate supply of heroin were not achieving the expected physical health and social functioning outcomes. His classic study (see also Druglink article) reported that while clients prescribed heroin attended the clinic more often and showed some reduction in criminal activity, other outcomes such as work, accommodation and diet did not differ from those denied a heroin prescription. The work sparked a debate which ultimately led to many clinics moving to a more interventional therapeutic approach (detox and rehab) and a refusal to prescribe injectable drugs to new patients. However, as Dr Mitcheson reminded the audience, clinic notes did show that a small group did very well.
The following two presenters then captured the next stage of the story of the ‘British System’. As the tide changed against diamorphine and towards oral methadone, the North-West of England had a number of services prescribing diamorphine and methadone ampoules into the 1980s and 1990s. Dr Louise Sell was a Consultant Psychiatrist working in such a service in Manchester, and presented the findings from review of a cohort of patients who were still being treated with injectable methadone and injectable heroin (an increasingly rare prescribing practice at this point in time). Meanwhile, Dr Nicola Metrebian, a researcher from London, presented the findings from a UK survey of doctors with licences to prescribe diamorphine in 2000, just at the advent of the National Treatment Agency for Substance Misuse (NTA). This was combined with a retrospective casenote audit of 210 sets of patients’ case notes at 27 of the 42 (64%) drug clinics in England and Wales where diamorphine was prescribed by the doctor. At the time there appeared to be a general consensus that diamorphine was a treatment of last resort, for those with long histories of heroin use and injecting, and those who had not responded sufficiently well to previous other treatments. However, a small number of patients had been initiated on diamorphine without ever having previously received opiate treatments and some because they were experiencing problems injecting methadone. This snapshot of practice between 1970 and 2000 was completed by Basak Tas, who presented a review of rates of death in this population receiving pharmaceutical heroin, finding annual mortality rates as high as seen in untreated populations today and higher than in populations in treatments more typically provided today.
SESSION 2
By the start of the 21st Century, injectable diamorphine treatment had gone from being the most common form of prescribed treatment for opiate dependence in the UK to being rarely prescribed. However, the 2002 UK Drugs Strategy recognised the potential important contribution of heroin prescribing, and in 2003 the NTA published expert consensus guidance on patient eligibility criteria for IV treatment.
Much of the potential for using this new supervised injectable heroin treatment (often termed ‘Heroin Assisted Treatment, HAT) for a select, entrenched group of heroin users came from studies conducted in Europe. Prof Ambros Uchtenhagen was perhaps the key instigator of this work, and led the introduction of these new supervised heroin clinics across in Switzerland. This was in response to a growing proportion of heroin users not in treatment in spite of the availability of drug-free treatment and agonist assisted therapy that had prompted concerns about the image of an otherwise well organised society. The Swiss studies did not adopt the traditional ‘British System’ approach, but rather introduced programmes where all injectable medication had to be injected at the clinic under medical supervision, often requiring twice or thrice daily attendance for heroin. To tide them over at night (or if they could not attend for their injection), patients were also prescribed oral methadone to be taken at home. The results were very promising, and led to research trials in other countries in Europe and beyond [see EMCDDA monograph]..
As Prof Eilish Gilvarry explained, by 2009 some of this work had led to a very different perception of the potential place and utility of heroin prescribing in the British treatment system. With the research funded by Action on Addiction (from a grant secured from the Community Fund; later the Big Lottery) and with clinical service support from the Home Office, Department of Health (DH) and the NTA, the Randomised Injectable Opioid Treatment Trial (RIOTT) in England had established three entirely new supervised injecting clinics, open twice per day, every day of the year, following the recommendations of the 2002 UK Drug Strategy. Prof Gilvarry led an expert group reviewing the evidence for heroin maintenance, convened by the NTA, and were provided with advance interim results (later published here) which showed that treatment with supervised injectable diamorphine led to significantly lower use of street heroin than did supervised injectable methadone or optimised oral methadone. Data from the RIOTT study (discussed here and in detail in SESSION 3), combined with 5 other RCTs led a new expert group to conclude that prescribing of injectables may be beneficial for a minority of heroin users, provided it was delivered in this new, more structured form of service. An important contribution of the conclusions from the 2009 Expert Group was that, while there was only a minimal evidence base for ‘Old British System’ un-supervised heroin prescribing (largely because of the absence of well-designed research trials), the scientific evidence was actually strong for the new type of supervised heroin prescribing clinics (with complete supervision of heroin doses), with half a dozen randomised trials now conducted in different countries over a two-decade period.
The remainder of the session focussed on how this was delivered in practice. Rob van der Waal described the practicalities of how this worked in practice in the London clinic used in the RIOTT study. The London RIOTT clinic drew heavily on the developments and operational practices of the supervised heroin clinics in Switzerland and the Netherlands, and functioned as the blueprint for the subsequent opening and operation of the other supervised injectable maintenance clinics in England (Brighton and Darlington). These new clinics functioned in ways very different from standard addiction treatment services in the UK – they were open seven days per week, 365 days per year and they had to clearly demarcated opening times (a morning session and the late afternoon session). With the frequency of contact, strong supportive relationships were usually developed, even though strict safety precautions were applied both to avoid risk of possible overdose (e.g. with other drugs or alcohol had been used to excess) and also to avoid any risk of drug diversion. In practice, and in a way that almost seemed paradoxical, the comparative rigidity of the clinic allowed the developments of freedom within the therapeutic relationships that were established, and these proved increasingly important as non-medication aspects of treatment and recovery became more relevant to work with patients receiving this new type of heroin treatment.
This potential to incorporate ‘recovery work’ within the RIOTT-style clinics was subsequently developed more explicitly, and Dr Tim Leighton finished the session by describing the processes that ran alongside the London injectable clinic that aimed to help users build recovery capital through a peer-mentor led intervention. this finding of the feasibility of ‘recovery work’ within this form of treatment points to the important need for, and feasibility of, incorporation of wider psychosocial interventions, even when developing and providing the treatment where it is the challenging nature of the medication prescribed (diamorphine/heroin) which attracts public and political interest. This session concluded with a realisation of the feasibility and importance of including elements from 12-step recovery approaches (and similar) within the overall therapeutic approach to be taken within a supervised heroin clinic.
During the lunch-break, two videos were shown, created at the time of conduct of the RIOTT trial. The first video (see below) was made by Action on Addiction, the addictions charity with whom the RIOTT trial team had secured the research funding – this video introduces the trial objectives, the researchers and clinicians, and interim comments from patients in the trial. The second video was made by South London & Maudsley (SLaM) NHS Foundation Trust and explains the purpose and the methods within the trial.
SESSION 3
The afternoon session began by stepping back to review in detail the design, results and conclusions from the RIOTT study, the UK’s contribution to the growing body of research about HAT (for published overviews, see EMCDDA Insights Monograph and also the ‘heroin on trial’ systematic review and meta-analysis.
Prof John Strang described the background and design, The RIOTT trial had been a randomised clinical trial, testing whether supervised injectable heroin treatment all supervised injectable methadone treatment might be more successful than regular oral methadone maintenance treatment (appropriately optimised) in terms of enabling an effective break with entrenched ongoing use of street heroin. The subjects recruited into the trial were typically long-term entrenched heroin addicts for whom orthodox treatments have failed to produce the expected benefits, and all had been in oral methadone treatment for at least the preceding six months and yet were continuing to inject street heroin regularly. A new laboratory test for street heroin (to differentiate from pharmaceutical heroin) was developed to corroborate self-report LINK. The pre-declared primary outcome which defined a ‘responder’ was that they were, during months 4-6 of treatment, using street heroin on less than half of the days per month: additional analyses also reported on the proportions in testing indicated that they had completely quit use of street heroin. The key findings were that substantially greater quitting the street heroin use was seen being individuals randomised to supervise the injectable heroin, amongst whom more than two thirds were ‘responders’, compared to less than a third of the other two groups, and a similar pattern was seen when the more severe measure of abstinence from street heroin was applied in the additional analysis LINK. A striking additional feature of the results was that, for those showing a good response, this was typically evident within the first 6 to 8 weeks of treatment – a finding of potentially major clinical significance in terms of future testing of what you wrote to derive benefit.
Dr Nicola Metrebian reported, for the first time, the findings from three-year follow-up study of patients in the RIOTT trial, drawn from work undertaken with PhD student Vicky Brooks. Interesting patterns of consolidation of benefit were seen, with continued recovery and quitting of involvement with street heroin use, and with early changes in the extent of reliance on the supervised injecting clinic, such as voluntary reduction to once-daily attendance, and moved to scheduled attendance patterns of less than daily (with oral maintenance cover provided either with oral methadone or supervised oral slow-release morphine). Analyses of these longer-term outcomes, as conducted with the cohorts in the other trials, will add richness to value of the findings from the originating randomised trials.
Dr James Bell gave an overview of the published qualitative research on the patient perception of heroin assisted treatment, concluding that although many users were drawn to heroin-assisted treatment in the hope of a euphoric effect, many experienced little euphoria from prescribed heroin. Dr Bell also described the changed nature of the relationship between patient in clinic staff as treatment proceeded, with the medication becoming less of a focal point and with the wider recovery work becoming more important. However the diversity of individual recovery journeys needs to be recognised and good clinical practice requires sensitive tailoring of this work to the characteristics and needs of the individual.
Prof Sarah Byford described the findings of the health economic evaluation, also explaining the principles of such analyses. Health economic analysis examines the health gain achieved across various domains, calculated against cost of the treatment provided. It is crucially different from simplistic examination of the cost of treatment delivery. It thus provides a means of integrating consideration of the effectiveness of the treatment (and the gain derived) with the cost of delivering the treatment. In contrast to clinical effectiveness findings (where supervised injectable heroin treatment clearly delivered the strongest gains), supervised injectable methadone treatment emerged as the least comparable to supervised injectable heroin treatment when measured for health benefits against costs incurred. Those responsible for planning and commissioning of services, as well as treating clinicians and patients, will need to integrate evidence from reports of clinical effectiveness alongside health economic analyses.
In the final contribution to session 3, Prof John Strang presented, on behalf of coinvestigators Dr Caroline Jolley, Basak Tas and others, preliminary data from studies of self-administration of intravenous and intramuscular diamorphine (prescribed pharmaceutical heroin). These studies have been undertaken with participation of patients receiving injectable diamorphine maintenance, and thus the examinations, in experimental test settings, actually examine the extent of respiratory depression associated with the drug administration that is occurring at least daily with these patients. Intravenous administration produces a more pronounced reduction in oxygen saturation levels in the blood (compared with intramuscular administration), and the effect varies substantially between individuals, and also to some extent between sessions. Current ongoing work examines the dose-sensitivity of this response, with examination also of respiratory flow, blood CO2 levels and neuro-respiratory drive. In this ongoing work, marked abnormalities of respiratory pattern are seen within a few minutes and remain detectable often for at least an hour. This research study is ongoing, but is likely to have implications for clinical safety monitoring of supervised injectable heroin treatment.
SESSION 4
The final session of the day presented a number of perspectives on issues around implementation of Heroin Assisted Treatment from across the world.
Dr Beau Kilmer, co-director of the RAND Drug Policy Research Center, presented an overview of the situation in the US and the current investigation by RAND of the possible need for supervised heroin treatment as part of the response to the extreme health crisis of rapidly escalating opioid overdose deaths. Dr Kilmer described the growing problem of increasing numbers of deaths over the last 20 years from overdose of prescription opiates, further complicated by the recent rapid increase in overdose deaths associated with heroin and also with, in the last couple of years, increasingly prevalent illicitly manufactured fentanyl (and fentanyl analogues). In the context of planning for multipronged public-health responses, RAND is examining the possible need for inclusion of supervised injectable heroin treatment programs for those who do not seem to be reached effectively from existing forms of intervention. This work is ongoing and will be reported later in the year.
Dr Brian Kidd, a member of the expert group that wrote the 2017 UK Guidelines on Clinical Management of Drug Misuse and Dependence (the Orange Guidelines, or Orange Book), explained how the new evidence base for HAT had been incorporated into national guidance. Whilst the Orange Guidelines pay most attention to ways of improving existing established treatments, they also crucially inform the reader about the new treatment approaches for which good-quality research evidence has come to light and which commissioners and practitioners should consider when providing individually-relevant personalised assessment of treatment need, likely benefit and associated harms (including if dropping out of treatment, as well as if remaining in treatment). In this context, the new 2017 updated edition of the Orange Guidelines draws attention to the increasingly consistent research evidence of benefit from supervised injectable heroin treatment for this otherwise refractory population. “There is compelling evidence for making injectable opioid treatment (IOT), usually diamorphine (heroin), available for those who continue to be at risk despite optimised oral OST. A section of the OST treatment population, despite being given access to optimised treatment with oral opioid maintenance, can fail to make adequate progress and continue to be involved in high levels of injecting drug misuse and other risk-taking behaviour” (P113, Orange Guidelines 2017).
Ashley Bertie and Ben Twomey from the office of the West Midlands Police and Crime Commissioner described how their recent review had concluded that prescribing heroin in a medical setting to people suffering from addiction who have not responded to other forms of treatment should be introduced. Having examined the evidence (including much of the evidence reported in this conference), they are struck by the therapeutic potential of supervised heroin treatment, especially when examined against the weak impact of standard law enforcement initiatives. In particular, the provision of better quality and more individually relevant treatments to those in need maybe a more effective way of interrupting the drug-crime relationship. Consequently the West Midlands police and crime Commissioner is now actively exploring whether a small-scale high-intensity supervised heroin treatment system should be included as part of the treatment response in the West Midlands area.
Finally, Carole Hunter presented the findings from a Glasgow Health & Social Care Partnership report that had recommended the introduction of HAT to tackle the growing problems associated with intravenous heroin in the city. She also distinguished these proposals from parallel recommendations for a safe injecting room in the city. A new outbreak of HIV infection in the city over the last two years, primarily associated with public injecting, particularly amongst disadvantaged populations, has prompted urgent consideration of alternative approaches. On behalf of colleagues Dr Saket Priyadarshi and Prof Sharon Hutchinson, Carole Hunter also described active current plans for introduction of a supervised injectable heroin treatment service for an otherwise treatment-refractory population, with plans for accompanying research trial study.
Prof John Strang brought the day to a conclusion with seven observations. His view was that the presentations throughout the day had concluded that we have an intensive treatment which is effective for a population otherwise non-responsive, or poorly responsive, to treatment. Despite funding pressures, we have a duty of care, which includes a duty to treat, and we are therefore failing to meet this responsibility both institutionally and individually. He urged the audience to continue the conversation with the goal of finding a resolution to provide this intensive treatment to those who do not otherwise benefit, especially in the light of the strength of international evidence of both clinical effectiveness and overall cost-effectiveness.
REFERENCES
Best, D., S. George, and E. Day, The Development of the Drug Treatment System in England, in Clinical Topics in Addiction, E. Day, Editor. 2007, RCPsych: London. p. 14-28.
Strang J & Gossop M (Eds.) Heroin Addiction and the British System: Treatment and Policy Responses (Volumes 1 and 2). 2004, Routledge.
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