In a recent Clinical Update editor Tom Jones summarises and comments on a primary care cohort study in the United Kingdom - a study that considers whether the use of methadone or buprenorphine as opioid substitution treatment (OST) was associated with a greater reduction in the risk of all-cause mortality and opioid drug-related poisoning mortality. In commenting on the paper, he considers the wider question - how do we retain patients on OST in treatment?


Hickman M., Steer C., Tilling K., Lim A. G., Marsden J., Millar T., Strang J., Telfer M., Vickerman P. & Macleod J. (2018) Addiction, 113(8): 1461-1476. doi: 10.1111/add.14188.

This primary care cohort study of 11,033 patients aimed to estimate whether the use of methadone or buprenorphine as OST was associated with a greater reduction in the risk of all-cause mortality (ACM) and opioid drug-related poisoning (DRP) mortality.

The authors found that rates of DRP were elevated during the first 4 weeks on OST, the first 4 weeks after cessation of OST, and the rest of the time off OST. Patients on buprenorphine have a lower risk of ACM and DRP compared to methadone during the first 4 weeks of treatment and the remaining time in treatment. However, treatment duration for patients on buprenorphine was shorter than that of those on methadone. This suggests that in UK primary care the reduced mortality risk observed during treatment on buprenorphine fails to translate to a population benefit, as the treatment duration is too short.

The authors observed an ageing and increasingly comorbid population with comparatively high rates of ACM. They refer to hypotheses that systemic illnesses may compromise physiological and pharmacological response to opioid action on respiratory depression and opioid metabolism, therefore increasing overdose risk. They suggest that buprenorphine has a greater effect on reducing mortality risk compared to methadone for this older and more comorbid cohort. But overall neither buprenorphine nor methadone are reducing the number of DRPs in the population.


How do we retain OST patients in treatment?

The findings of this study may be underwhelming, but they serve to highlight the importance of treatment retention. We know that initiation of OST can be a risky period for patients, requiring expertise in dose titration and close monitoring to avoid adverse events including DRP. We also know that when people stop OST, whether as part of a planned treatment exit or not, their opioid tolerance is lowered and they are more at risk of DRP. It is therefore important that we have services equipped with expertise in OST initiation and the resources to provide the psychosocial support that may improve treatment retention. 

This paper made reference to the fact that we are seeing an increasingly complex older population with more comorbidity, and that this may result in complications when treating with opioids. This is something that, anecdotally at least, I have observed in practice. The authors found that the risk of mortality is lower in older patients prescribed buprenorphine compared to methadone. Perhaps buprenorphine can be considered as a first-line treatment for older patients with multimorbidity (the presence of 2 or more chronic conditions). But of course, if the duration of treatment is too short, those same high-risk patients are then exposed to an elevated DRP risk post-OST. So perhaps there should be a particular focus on how to retain older patients with more comorbidity on buprenorphine.

The authors refer to a recent study that suggested that the prevalence of shorter treatment durations might be greater in the UK than elsewhere (Mukandavire et al., 2017). I have written previously about how retendering of substance misuse services can be a cause of confusion and frustration for our patients and, indeed, a reason that some may fall between the cracks and out of treatment. Changes in GP shared care arrangements may also have an effect on treatment retention in primary care, and may provide an additional source of confusion for patients. 

In summary, this paper states that the majority of drug-related deaths are among those not in treatment. It is therefore vital that we look at how we can retain people in treatment, particularly in an ever-changing healthcare landscape. Further qualitative evidence is required to elicit the reasons that people leave treatment, so that we can explore novel approaches to treatment retention and OST can have its intended benefits. 

Tom Jones, Sep 2018

Papers included in the full clinical update:

  • Impact of current and scaled-up levels of hepatitis c prevention and treatment interventions for people who inject drugs in three UK settings – what is required to achieve the WHO’s HCV elimination targets?

  • Baclofen in the treatment of alcohol dependence with or without liver disease: multisite, randomised, double-blind, placebo-controlled trial.

  • Pharmacokinetics of concentrated naloxone nasal spray for opioid overdose reversal: Phase I healthy volunteer study.

  • Patterns of peer distribution of injecting equipment at an authorized distribution site in Sydney, Australia.

  • Self-medication with alcohol or drugs for mood and anxiety disorders: a narrative review of the epidemiological literature.