Abstract
Methadone-related deaths are characterized by a wide range of post-mortem blood concentrations, due to the high pharmacokinetic/dynamic inter-individual variability, the potential subjective tolerance state and to other risk factors or comorbidities, which might enhance methadone acute toxicity. In the present study, the association among pre-existing and external conditions and diseases and the resultant methadone death capacity have been investigated. Beside a systematic literature review, a retrospective case-control study was done, dividing cases in which methadone was the only cause of death (controls), and those with associated clinical-circumstantial (naive/non-tolerant state), pathological (pulmonary or cardiovascular diseases) or toxicological (other drugs detected) conditions. Methadone concentrations were compared between the two groups and the association with conditions/diseases was assessed by multiple linear and binomial logistic regressions. Literature cases were 139, in house 35, consisting of 22 controls and 152 cases with associated conditions/diseases. Mean methadone concentrations were 2122 ng/mL and 715 ng/mL in controls and cases respectively, with a statistically significant difference (p < 0.05). Lower methadone concentrations (by 24, 19 and 33% respectively) were detected in association with naive/non-tolerant state, pulmonary diseases and presence of other drugs, and low levels of methadone (<600 ng/mL) might lead to death in the presence of the above conditions/diseases.
Highlights
The aim of the present study is to provide a contribution to the issue, bringing further statistical and epidemiological evidence regarding the causal and concausal role of pre-existing intrinsic conditions, such as methadone non-tolerance and cardio-pulmonary diseases, or external conditions, such as co-assumption of other psychotropic substances
The present study confirms the interest of the scientific community on the topic of methadone-involving fatalities and highlights the difficulties in the post-mortem interpretation of these deaths, due to several factors including pharmacokinetic and dynamic variability, tolerance and post-mortem redistribution
After a review of the relevant literature and a pooled analysis between literature and in house cases, it was found that deaths involving only methadone had higher concentrations than those so-called cases that presented additional clinical-circumstantial, pathological or toxicological conditions or diseases
Summary
Beside a systematic literature review, a retrospective case-control study was done, dividing cases in which methadone was the only cause of death (controls), and those with associated clinical-circumstantial (naive/nontolerant state), pathological (pulmonary or cardiovascular diseases) or toxicological (other drugs detected) conditions. Lower methadone concentrations (by 24, 19 and 33% respectively) were detected in association with naive/non-tolerant state, pulmonary diseases and presence of other drugs, and low levels of methadone (
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