Adjustment for dispensed doses does not explain higher antidepressant concentrations in post-mortem toxicology #MMPMID41351311
Lim JS; Noghrehchi F; Buckley NA; Schumann J; Cairns R
Br J Clin Pharmacol 2025[Dec]; ? (?): ? PMID41351311show ga
AIMS: Post-mortem detection of a medicine following suicide can be due to two main reasons: the decedent was taking that medicine therapeutically before death, and/or the medicine was involved in the suicidal act (poisoning-related suicide). We aimed to investigate how antidepressant concentrations differed between poisoning and non-poisoning suicides. We hypothesized that the predictive value of these concentrations and the separation between poisoning and non-poisoning concentrations would improve by adjusting for dose dispensed to the decedent. METHODS: We analysed post-mortem toxicology results from suicides in Australia, July 2013 to October 2019, linked to the individual's dispensing history. Suicides were classified as poisoning- or non-poisoning-related by coroners. We analysed the distribution of concentrations through descriptive statistics, precision-recall curves and quantile regression to compare poisoning and non-poisoning concentrations. We adjusted concentrations by estimated daily dose and total drug quantity dispensed in 90 days and re-assessed model performance. RESULTS: We had sufficient sample size to analyse nine antidepressants: amitriptyline (n = 149), mirtazapine (n = 399), citalopram (n = 116), escitalopram (n = 297), fluoxetine (n = 183), sertraline (n = 253), duloxetine (n = 122), venlafaxine (n = 261), desvenlafaxine (n = 194). Selective Serotonin Reuptake Inhibitor non-poisoning and poisoning concentrations were similar, with no high certainty threshold for poisoning for citalopram and sertraline. Amitriptyline had the best separation between poisoning and non-poisoning concentrations. Adjustment by estimated daily dose improved the separation of lower quantiles through quantile regression but did not help identify thresholds that separated poisonings and non-poisonings. CONCLUSIONS: Dose adjustment generally did not improve the separation of poisoning vs non-poisoning suicides, indicating that post-mortem concentrations may not have clear dose-concentration relationships.
Br+J+Clin+Pharmacol 2025 ; ? (?): ?
