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Adjustment for dispensed doses does not explain higher antidepressant concentrations in post-mortem toxicology
Jessy S Lim1,2,3, Firouzeh Noghrehchi1, Nicholas A Buckley1,2,4
1Biomedical Informatics and Digital Health, Faculty of Medicine and Health, The University of Sydney, Australia.
British Journal of Clinical Pharmacology
|December 6, 2025
Summary
Post-mortem antidepressant concentrations in suicide cases showed limited separation between therapeutic use and poisoning. Adjusting for dispensed dose did not significantly improve the ability to distinguish between poisoning and non-poisoning suicides.
Area of Science:
- Forensic Toxicology
- Psychopharmacology
- Suicidology
Background:
- Post-mortem drug concentrations can reflect therapeutic use or poisoning in suicide cases.
- Distinguishing between these two scenarios is crucial for accurate interpretation of toxicology findings.
- Antidepressant concentrations in post-mortem samples require careful analysis to differentiate therapeutic levels from overdose-related suicides.
Purpose of the Study:
- To investigate differences in post-mortem antidepressant concentrations between poisoning-related and non-poisoning suicides.
- To evaluate whether adjusting concentrations by dispensed dose improves the distinction between these suicide types.
- To assess the predictive value of antidepressant concentrations in determining the role of the drug in suicide.
Main Methods:
- Analysis of post-mortem toxicology results from Australian suicides (July 2013-October 2019).
- Linking toxicology data with individual dispensing history.
- Classification of suicides as poisoning- or non-poisoning-related.
- Statistical analysis including descriptive statistics, precision-recall curves, and quantile regression.
- Adjustment of concentrations by estimated daily dose and total dispensed quantity.
Main Results:
- Nine antidepressants (amitriptyline, mirtazapine, citalopram, escitalopram, fluoxetine, sertraline, duloxetine, venlafaxine, desvenlafaxine) were analyzed.
- Selective Serotonin Reuptake Inhibitor (SSRI) poisoning and non-poisoning concentrations were similar; no clear poisoning threshold for citalopram and sertraline.
- Amitriptyline showed the best separation between poisoning and non-poisoning concentrations.
- Dose adjustment improved separation in lower quantiles but did not establish clear thresholds.
Conclusions:
- Dose adjustment generally did not enhance the separation between poisoning and non-poisoning suicides.
- Post-mortem antidepressant concentrations may lack clear dose-concentration relationships in suicide cases.
- Further research is needed to refine the interpretation of post-mortem antidepressant levels in suicide investigations.
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