Scotland’s 2009-2015 methadone-prescription cohort: quintiles for daily-dose of prescribed methadone and risk of methadone-specific death

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Background: 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; 1323 DRDs (42%), 546 being methadone-specific DRDs. 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 >90mg. Age 45+ years at cohort-entry (hazard ratio versus 25-34 years: 3.1, 95% CI: 2.4-4.2), top quintile for baseline daily-dose of prescribed methadone (versus 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. Conclusions: Extra care is needed when methadone daily-dose exceeds 90mg. 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 gender. 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.
Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
DOIs
Publication statusPublished - 12 Jun 2020

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