New findings on older age as risk-factor for methadone-specific deaths

New findings in Drug and Alcohol Dependence about older age as a risk-factor for methadone-specific deaths in Scotland have been published by a team of specialists in biostatistics, pharmacy, and addictions who were led by Professor Sheila M. Bird of the Medical Research Council’s Biostatistics Unit (BSU).

Professor Bird said: “We studied a cohort of over 33,000 methadone-clients in Scotland between 2009 and 2013 who experienced 760 DRDs, of which 362 were methadone-specific DRDs*. On average, there were 3 methadone-specific deaths per 1000 person-years of follow-up.

We discovered, however, that the hazard of methadone-specific DRD increased more steeply with age-group (defined as: under 25 years, 25-34 years, 35-44 years, 45+ years) than did the hazard for all DRDs.  And there was no gender differential.”

“These new findings - on clients’ age and also on the quantity of methadone prescribed – are thanks to Scotland’s excellent record-linkage capabilities and a national protocol for toxicology at drugs-related deaths. But their impact is international.

For methadone-specific DRDs, the hazard-escalators, relative to 1 at 25-34 years, were 1.9 (95% CI: 1.5 to 2.4) at 35-44 years and 2.9 (95% CI: 2.1 to 3.9) at 45+ years.

For all DRDs, the corresponding hazard escalators were less steep, being 1.4 (95% CI: 1.2 to 1.7) and 1.9 (95% CI: 1.5 to 2.4).

In 2006, the UK’s Medicines and Healthcare products and Regulatory Authority recommended electrocardiograms for older or persistent methadone clients on higher doses. Our results suggest a need for electrocardiograms for older methadone clients irrespective of prescribed dose.”

Background: Methadone has accounted for the vast majority of Scotland’s opioid substitution therapy over the past 30 years. Methadone prescribing in Scotland has been under scrutiny because the drugs-related deaths (DRDs) in which methadone was implicated were increasing. The Scottish Drug Strategy Delivery Commission (2013) endorsed the value of methadone as a treatment which halves clients’ risk of DRD and reduces blood-borne viruses and recourse to criminality.

The researchers also found that, for clients whose baseline prescribed quantity of methadone was in the top 20% (versus bottom 20%), the risk of methadone-specific DRD was increased by a factor of 1.8 (95% CI: 1.3 to 2.5).

This dose-related finding is consistent with similar results reported from the USA for patients who had received methadone as a prescribed opioid for chronic pain.

Professor Bird added: “Causal explanation for the strong age-relatedness of methadone-specific DRDs is, as yet, unclear. Co-morbidities, including carriage of the Hepatitis C virus, may be implicated; or QTc prolongation which can be detected by electrocardiogram.”

We have conjectured that 5% to 10% of older methadone clients could have QTc prolongation. If these older methadone clients were willing to attend for electrocardiograms, then that proposition could be tested robustly in as few as 200 electrocardiograms. But, we’d need the help and co-operation of older methadone clients to do so.”

Professor Bird cautioned: “Of course, empirical findings which are a first, as these are, need to be validated. Two types of validation are already underway.

The first is based on prescribed clients in England’s National Drug Treatment Management System who experienced 271 methadone-only deaths in 2005 to 2009. The second is extension of Scotland’s methadone-prescription cohort from 2013 to 2015. The first test has already been passed - thanks to colleagues at Manchester University who were part of an MRC-funded addictions cluster on quantifying drugs harms.”

The other disciplinary leads were Professor Marion Bennie of Strathclyde University’s Institute of Pharmacy and Biomedical Sciences and Professor Roy Robertson from Edinburgh University’s Usher Institute of Population Health Sciences and Informatics.

To read the full paper, go to:

*Methadone-specific DRD was defined as:  methadone was implicated in DRD but neither heroin/morphine nor buprenorphine was implicated in the death.

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