Multi-matrix postmortem distribution in fatal venlafaxine-mirtazapine intoxication

We describe a fatal case of combined venlafaxine-mirtazapine poisoning in a 33-year-old man with schizoaffective disorder, who was found dead at home next to empty venlafaxine blister packs. Systematic toxicological screening (LC-MS/MS and full-scan GC-MS) identified venlafaxine, O-desmethylvenlafaxine, mirtazapine, N-desmethylmirtazapine, delorazepam and lorazepam; these analytes were subsequently quantified in central blood, peripheral blood, urine, brain and liver using a validated LC-MS/MS method, and intact venlafaxine tablets were also recovered from the gastric/duodenal content. In peripheral blood, venlafaxine measured 4.42 mg/L and mirtazapine 0.72 mg/L: both above therapeutic ranges yet below the lowest concentration reported in any published fatal case of either drug alone, pointing to an additive, likely synergistic, toxic interaction between the two compounds; delorazepam and lorazepam, by contrast, remained at therapeutic concentrations. The cause of death was attributed to acute combined venlafaxine-mirtazapine overdose, and the manner of death was classified as suicide. To the best of our knowledge, this represents the first reported fatal venlafaxine-mirtazapine co-ingestion with multi-matrix post mortem quantification, and only a handful of previous cases have documented venlafaxine concentrations in brain tissue after a fatal overdose.