Adjustment for dispensed doses does not explain higher antidepressant concentrations in post‐mortem toxicology

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.