Deaths on methadone: Analysis of demographics and concentrations of methadone and EDDP in post-mortem femoral blood samples collected over an eighteen-year period in Western Switzerland and their relationship to the cause of death.

Author: Georgi Pecev, Gaëlle Magliocco, Marc Augsburger, François Girardin, Aurélien Thomas

Theme: Clinical Research Year: 2023

Methadone is a synthetic opioid indicated for opioid withdrawal treatment. Its main metabolite is 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Since methadone is a potent drug with a low therapeutic index, this study aims at determining the post-mortem blood concentrations of methadone and EDDP in methadone-related deaths caused by either methadone intoxication or by other causes with concomitant presence of methadone.

Methadone and EDDP concentrations were measured by GC-NPD, HPLC-DAD, GC-MS and LC-MS/MS in the post-mortem blood of cases under methadone collected from 2000 to 2017 in Western Switzerland. For each case, a full autopsy was conducted to establish the cause of death. All statistical analyses were performed using R Statistical Software.

The dataset consists of 285 individuals (84 women and 201 men). The average methadone blood concentration is 650.53 ± 724.67 ng/mL, with 684.46 ± 710.73 ng/mL for women and 636.20 ± 731.77 ng/mL for men (P = 0.606). The average EDDP concentration is 179.96 ± 515.40 ng/mL, with 103.21 ± 114.61 ng/mL for women and 211.23 ± 605.13 ng/mL for men (P = 0.078). 78.6 % of deaths are due to methadone intoxication, including a majority of polyintoxications, and 21.4% of deaths are due to other causes (self-aggression, hetero-aggression, trauma, pathologies) with concomitant methadone use. Between these two groups, methadone concentrations are significantly higher in subjects who died of intoxication (675.76 ± 767.87 ng/mL) compared to those who died of another cause while on methadone (509.68 ± 430.20 ng/mL) (Welch Two Sample t-test, P < 0.05). We did not find any significant difference in EDDP levels for these same two groups.

We found higher methadone blood concentrations in patients who died of methadone intoxication compared to patients who died of another cause while on methadone.

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