Theme: Clinical Research Year: 2023
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
We found higher methadone blood concentrations in patients who died of methadone intoxication compared to patients who died of another cause while on methadone.