The road less travelled

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Methadone’s dominance over Suboxone in substitute prescribing may have more to do with cost than effectiveness. It could be time for a reassessment, say Neil McKeganey, Christopher Russell and Lucy Cockayne

Within the drug treatment field there are few more controversial subjects than the role of substitute prescribing. For some people, drugs such as methadone and Suboxone represent a lifesaver, enabling individuals to reduce or cease their use of street drugs and stabilise their lives as a prelude to their eventual recovery and rehabilitation. For others, the prescription of these drugs on a maintenance basis is little more than a form of state-sponsored addiction.

The importance given to recovery in the UK drug strategy has brought renewed attention to the role of substitute prescribing, with the NTA recently publishing revised guidance on how to maximise the beneficial impact of opiate substitute treatment within a recovery-oriented treatment system.

In the period since the mid-1960s, when Vincent Dole and Marie Nyswander undertook groundbreaking work, methadone has become the mainstay of addictions treatment in countries across the globe. In the UK it is estimated that something in the region of 166,000 drug users are receiving opiate substitution treatment, the vast majority of whom are being prescribed methadone.

We know from research that methadone reduces drug users’ risk of overdose, needle and syringe sharing, and of becoming HIV and HCV positive. Research in Edinburgh has also shown that drug users who are prescribed methadone have a significantly reduced risk of dying from drug-related causes (Kimber et al, 2010). We also know that drug users prescribed methadone commit fewer crimes, remain in contact with drug treatment services for longer and have a more stabilised lifestyle. But what we do not know is how good methadone is at enabling individuals to recover from being psychologically or physically dependent on opiate drugs.

The Edinburgh based research undertaken by Kimber and colleagues gave some cause for concern in this respect, with evidence showing that methadone may lengthen, rather than shorten, the period over which individuals remain drug dependent. The drug users who had been prescribed methadone in this general practice based study had a mean injecting career of some 20 years compared to a mean of nearer five years for those who had not been prescribed methadone. ‘Exposure to opiate substitution treatment was,’ the authors pointed out, ‘inversely related to the chances of achieving long term cessation.’

Along with the worry that methadone may lengthen the duration of an individual’s dependency, there has also been growing concern at the increasing proportion of drug-related deaths that are in some way connected to methadone. In Scotland, for example, some 47 per cent of drug user deaths were recently shown to be connected with methadone (DDN, September, page 4), although it’s not known what proportion of those deaths involved individuals who had sourced their methadone on the streets rather than being prescribed the drug.  
In the light of those concerns it’s understandable that attention has come to focus on other substitute medications that may offer some of the benefits of methadone without the additional risks. One such drug, the buprenorphine/ naloxone combination Suboxone, has been licensed for use in Europe since 2006.  

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According to the National Institute for Health and Clinical Excellence (NICE) there is very little difference between buprenorphine and methadone in terms of their therapeutic effect and therefore, according to NICE, the decision as to which drug to prescribe should be based upon an assessment of the individual drug user’s circumstances.

On the basis of that advice one might have thought that Suboxone and methadone would by now be prescribed at a broadly similar rate. This is certainly the case in Norway, with methadone prescribed to 56 per cent of those receiving opiate substitution treatment compared to 44 per cent who are on Suboxone. In Sweden, 48 per cent of those on opiate substitution treatment are receiving methadone, compared to 52 per cent who are being prescribed Suboxone.

The picture in other European countries, though, is strikingly different. In Germany, 81 per cent of opiate substitution prescriptions are for methadone compared to 19 per cent for Suboxone. In Denmark, the proportions are 82 per cent for methadone and 16 per cent for Suboxone, and within Scotland it has been estimated that there are around 22,224 drug users being prescribed methadone compared to what is likely to be only a few thousand being prescribed Suboxone. Similarly, within England, the vast majority of those drug users on opiate substitution treatment are being prescribed methadone rather than Suboxone.

The preponderance of methadone over Suboxone prescribing in some countries but not others is puzzling and may have more to do with the relative price of the two drugs than their therapeutic effect. NICE, for example, has advised that because methadone is the cheaper of the two drugs it should be the first-line treatment. Similarly, the national clinical guidelines (‘orange book’) reiterate the view that if both treatments are equally suitable methadone should be the first choice treatment. Within a treatment culture focused on enabling drug users to become drug free, however, there may be a reason for considering the wider use of Suboxone.  

In recent research in Scotland, drug users prescribed Suboxone were substantially more likely to have experienced a drug-free period than were those prescribed methadone (McKeganey et al 2012). In this study the researchers followed two groups of drug users over an eight-month period – one group had been prescribed methadone and the other Suboxone. Importantly this was not a randomised controlled trial and the total number of drug users followed – at 109 – was not large. Nevertheless the findings from the study research were striking.

The two groups of drug users were similar in terms of their age, gender, number of days they had been using heroin over the last three months, and the ages at which they began using heroin and at which their heroin use became a problem. The groups were also similar in their desire to be helped and in their mental health. Where the groups differed was in their readiness for treatment, with the Suboxone group scoring higher than those being prescribed methadone on this measure.

Despite the multiple similarities between the two groups they differed markedly in terms of their treatment outcomes. In the case of those drug users prescribed Suboxone, the mean number of days on which they used heroin over the last three months fell from 38.6 days at study intake to 8.5 days at the eight-month interview point. In the case of the methadone patients the reduction was from 37.4 days at intake to 24.1 days at the eight-month interview point. Whilst both Suboxone and methadone were associated with a significant reduction in the frequency of heroin use, the effect size for Suboxone was substantially greater than that for methadone. Both treatments were similarly effective in enabling drug users’ attempts to remain drug free (preventing relapse) where the individual had ceased his or her drug use at the outset of the study.

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Within a treatment culture where increasing attention is being directed at becoming drug free, and where there is mounting concern at the increasing proportion of drug-related deaths associated in some way with methadone, Suboxone may come to be prescribed much more widely within the UK even despite its greater cost, and we may come to see much closer parity between the two drugs as part of an opiate substitution treatment regime.

The research described in this article was supported by an unrestricted, unsolicited investigator-initiated request from Reckitt Benckiser who had no role in study design, data collection, analysis, interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication.

Neil McKeganey and Christopher Russell are based at the Centre for Drug Misuse Research, Glasgow. Lucy Cockayne is consultant psychiatrist in addictions at Spittal Street Centre, Edinburgh