A postmortem paroxetine concentration of 3.3 mg/L supported poisoning in a reported mixed-drug fatality, but did not diagnose serotonin syndrome. The authors specifically stated that they could neither document nor exclude serotonin syndrome or an arrhythmic mechanism. Their cause-of-death conclusion combined toxicology with the scene, history and examination.
The specimen was external iliac blood
Florou and colleagues described a 22-year-old man found dead after treatment for psychiatric illness. The scene included empty or partly empty medication packages. Death was estimated at 18–24 hours before discovery; transfer to the mortuary occurred eight hours after discovery, and autopsy 12 hours after transfer. These were estimated and documented intervals, not a precisely known ingestion-to-death timeline.
Autopsy specimens were blood from the left external iliac vein, bladder urine and gastric contents. The blood was not femoral blood and not serum. It was collected in a 2 mL tube containing 5 mg sodium fluoride and 4 mg potassium oxalate. Samples remained at 4°C while analyses were completed within two weeks, then were retained at −20°C for possible reanalysis.
Early putrefactive changes were present. Histology was not performed because of the tissue condition. Cerebral and pulmonary edema and lung congestion were described, without a specific structural finding establishing serotonin toxicity.
Screening and quantification were different procedures
The investigation included immunoassay screening, full-scan GC–MS toxicological screening and headspace GC–FID for ethanol. Paroxetine was quantified by LC–MS/MS, with the blood procedure modified for urine and gastric-content work. Analyses were performed in triplicate.
The reported paroxetine concentration was 3.3 mg/L in blood and approximately 1.6 mg/L in urine; the abstract gives the more precise urine value of 1.58 mg/L. Table 1 expresses concentrations in µg/mL, numerically equivalent to mg/L. This unit equivalence does not make blood, urine and serum biologically interchangeable.
The case report did not reproduce numerical detection limits, quantitation limits, calibration ranges or precision data for the modified analyses. Triplicate testing is useful but does not, by itself, establish every aspect of quantitative validation in each matrix.
What else was detected?
Table 1 reports alprazolam at 0.038 µg/mL, alpha-hydroxy-alprazolam at 0.0056 µg/mL and quetiapine at 0.0013 µg/mL in blood. Norclozapine was reported in urine at 0.0165 µg/mL, without a corresponding positive blood entry. Gastric drug findings were qualitative, not a measured recovered dose.
The authors described alprazolam as within a referenced therapeutic range and quetiapine as below it, while considering them possible contributors in combination with paroxetine. Neither a therapeutic-range comparison nor detection alone establishes the magnitude of a drug interaction in one deceased person.
Why mechanism remained unresolved
Serotonin syndrome is not established by identifying an SSRI or by assigning a concentration to it. This report lacked the clinical observations needed to demonstrate that syndrome before death. The authors also could not document QT prolongation or ventricular arrhythmia as the mechanism.
They attributed the death to mixed-drug intoxication with paroxetine as the primary toxicant and described additive or synergistic contributions from other medications. That was an integrated case interpretation, not an experimentally quantified interaction or a statistical comparison between exposed groups.
Postmortem change prevents an exact reconstruction
The authors acknowledged that putrefaction and redistribution could have altered concentrations in either direction. Peripheral collection reduced some concerns but did not establish an unchanged antemortem concentration. There was no paired predeath specimen or serial postmortem study from which to calculate the individual’s change.
The case therefore supplies no universal lethal cutoff, ingested dose, ingestion time or impairment threshold. The appropriate conclusion preserves the measured result and specimen history while separating the authors’ poisoning attribution from the unproven mechanism.
Related interpretation issues appear in clozapine detection and causal attribution and matrix-dependent parent/metabolite ratios.
Primary source
Florou D, et al. Poisoning suicide due to paroxetine overdose toxicity aided by benzodiazepine and antipsychotic drugs. International Journal of Legal Medicine. 2025;139:2713–2719. doi:10.1007/s00414-025-03570-7.
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