Scotland's 2009–2015 methadone-prescription cohort: Quintiles for daily dose of prescribed methadone and risk of methadone-specific death

AIMS: As methadone clients age, their drug-related death (DRD) risks increase, more than doubling at 45+ years for methadone-specific DRDs. METHODS: Using Community Health Index (CHI) numbers, mortality to 31 December 2015 was ascertained for 36 347 methadone-prescription clients in Scotland during 2009–2015. Cohort entry, quantity of prescribed methadone and daily dose (actual or recovered by effective, simple rules) were defined by clients' first CHI-identified methadone prescription after 30 June 2009 and used in proportional hazards analysis. As custodian of death records, National Records of Scotland identified non-DRDs from DRDs. Methadone-specific DRD means methadone was implicated but neither heroin nor buprenorphine. RESULTS: The cohort's 192 928 person-years included 1857 non-DRDs and 1323 DRDs (42%), 546 of which were methadone specific. Actual/recovered daily dose was available for 26 533 (73%) clients who experienced 420 methadone-specific DRDs. Top quintile for daily dose at first CHI-identified methadone prescription was >90 mg. Age 45+ years at cohort-entry (hazard ratio vs 25–34 years: 3.1, 95% confidence interval: 2.4–4.2), top quintile for baseline daily dose of prescribed methadone (vs 50–70 mg: 1.9, 1.1–3.1) and being female (1.3, 1.0–1.6) significantly increased clients' risk of methadone-specific DRD. CONCLUSION: Extra care is needed when methadone daily dose exceeds 90 mg. Females' higher risk for methadone-specific DRD is new and needs validation. Further analyses of prescribed daily dose linked to mortality for large cohorts of methadone clients are needed internationally, together with greater pharmacodynamic and pharmacokinetic understanding of methadone by age and sex. Balancing age-related risks is challenging for prescribers who manage chronic opiate dependency against additional uncertainty about the nature, strength and pharmacological characteristics of drugs from illegal markets.