Risk-factors for methadone-specific deaths in Scotland's methadone-prescription clients between 2009 and 2013*

•Powerful analysis of a national cohort's 362 methadone-specific deaths.•Scottish cohort of 33,128 methadone-prescription clients in 2009-2013.•Steeper age-gradient than for all drugs-related deaths.•No gender differential in the hazard of methadone-specific deaths.•Increased hazard at the highest quintile for quantity of methadone prescribed.

AimTo quantify gender, age-group and quantity of methadone prescribed as risk factors for drugs-related deaths (DRDs), and for methadone-specific DRDs, in Scotland's methadone-prescription clients.DesignLinkage to death-records for Scotland's methadone-clients with one or more Community Health Index (CHI)-identified methadone prescriptions during July 2009 to June 2013.SettingScotland's Prescribing Information System and National Records of Scotland.MeasurementsCovariates defined at first CHI-identified methadone prescription, and person-years at-risk (pys) thereafter until the earlier of death-date or 31 December 2013. Methadone-specific DRDs were defined as: methadone implicated but neither heroin nor buprenorphine. Hazard ratios (HRs) were assessed using proportional hazards regression.FindingsScotland's CHI-identified methadone-prescription cohort comprised 33,128 clients, 121,254 pys, 1,171 non-DRDs and 760 DRDs (6.3 per 1,000 pys), of which 362 were methadone-specific. Irrespective of gender, methadone-specific DRD-rate, per 1,000 pys, was higher in the 35+ age-group (4.2; 95% CI: 3.6-4.7) than for younger clients (1.9; 95% CI: 1.5-2.2). For methadone-specific DRDs, age-related HRs (e.g., 2.9 at 45+ years; 95% CI: 2.1-3.9) were steeper than for all DRDs (1.9; 95% CI: 1.5-2.4); there was no hazard-reduction for females; no gender by age-group interaction; and, unlike for all DRDs, the highest quintile for quantity of prescribed methadone at cohort-entry (>1960 mg) was associated with increased HR (1.8; 95% CI: 1.3-2.5).ConclusionHigher methadone-specific DRD rates in older clients, irrespective of gender, call for better understanding of methadone's pharmaco-dynamics in older, opioid-dependent clients, many with progressive physical or mental ill-health.