Antidepressant metabolite concentrations and metabolite-to-parent drug ratios in postmortem femoral blood

Antidepressants are commonly used psychiatric medications, many of them associated with significant toxicity in overdose. While established reference values are used in therapeutic monitoring of these drugs, there are less abundant reference data available in postmortem (PM) toxicology, especially concerning antidepressant metabolites. In this study, all such PM cases in 2016-2023 were retrieved from the Finnish national PM toxicology database in which an antidepressant drug and its metabolite were quantified concurrently in femoral venous blood, representing all causes of death (N = 3472). The results comprise the median concentrations of 11 antidepressants and their main metabolites, the parent drug plus metabolite sum concentrations, and the respective metabolite-to-parent drug ratio (MPR) values. The study revealed that the concentrations of antidepressants and their metabolites in PM blood generally increase in the following order according to the group studied: other cause of death than poisoning < implicated in fatal poisoning < principal finding in fatal antidepressant poisoning < single finding in fatal antidepressant poisoning. MPR was found to be a useful addition to concentration values in distinguishing acute poisoning death from other causes of death, showing lower MPR values in poisoning, and the results obtained in this study compared favorably with data previously published in the literature. The parent drug plus metabolite sum concentration did not provide significant additional information to parent drug only in PM diagnostics of poisoning.