A case of lacosamide and mirtazapine self-poisoning

•This report describes a case of poisoning death due to simultaneous high doses of lacosamide and mirtazapine.•Lacosamide has been widely used for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal level of blood concentrations.•LC/ESI–MS/MS method for the quantification of lacosamide and mirtazapine was developed.•Blood level of lacosamide was approximately 10 times higher than the therapeutic level.•Increased blood levels and resulting cardiac toxicity caused by the inhibition of a common drug-metabolizing enzyme of both drugs may have been the cause of death. Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization–tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 μg/mL and a mirtazapine concentration of 12.0 μg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.