Non drug-related and opioid-specific causes of 3262 deaths in Scotland's methadone-prescription clients, 2009-2015

Background: Opioid drug use is a major cause of premature mortality, with opioid substitution therapy the leading intervention. As methadone-clients age, non-drug-related deaths (non-DRDs) predominate and DRD-risks increase differentially, quadrupling at 45 + years for methadone-specific DRDs. Methods: 36,606 methadone-prescription-clients in Scotland during 2009-2015 were linked to mortality records to end-2015 by their Community Health Index (CHI). Cohort-entry, also baseline quantity of prescribed methadone, were defined by clients' first CHI-identified methadone-prescription during 2009-2015. National Records of Scotland identified non-DRDs from DRDs; and provided ICD10 codes for underlying and co-present causes of death. Methadone-specific DRD means methadone was implicated in DRD but neither heroin nor buprenorphine. Results: During 193,800 person-years of follow-up, 1939 non-DRDs (59%) and 1323 DRDs occurred, of which 546 were methadone-specific. Predominant underlying ICD10 chapters for non-DRDs were: neoplasm (377); external causes (341); diseases of digestive (303), circulatory (286) or respiratory (212) system. As methadone clients aged, the non-DRD proportion of their deaths increased from 54% (717/1318) at 35-44 years to 89% (372/417) at 55+ years. After allowing for DRDs' opioid-specificity, age-group and quintile for last-prescribed methadone, there was a significant, positive interaction for co-present circulatory disease between top-quintile for prescribed methadone and 45 + years at death (p = 0.033 after Bonferroni); not for digestive or respiratory co-presence. Conclusions: Circulatory disease is the co-morbidity most likely implicated in the quadrupling of methadone specific DRD-risk at 45 + years; followed by digestive disease. Cultural shift is needed in treatment-services because degenerative non-DRDs predominate as methadone-clients age. Future linkage-studies should access hospitalizations and methadone-daily-dose.