Death after probable misuse of several stimulants: Ethylphenidate (ETH), methylphenidate (MTH) and modafinil (MODA)

Objectif Prescription stimulant medications may be misused with consumption of illegal drugs of the same pharmacologic class. We describe the case of a man presenting at the time of his death blood impregnation of several stimulants: ethylphenidate, methylphenidate and modafinil. Case history A 37-year-old man, who presented bipolar disorders with psychiatric follow-up, was found dead at home. His usual treatment included MTH, MODA, clorazepate, amisulpride, sertraline and lamotrigine. The autopsy findings were nonspecific with only an acute asphyxia syndrome with a possible toxicological contribution, and no macroscopic heart abnormalities. Methods Large screenings of drugs and toxics were performed on autopsy peripheral blood samples. Results Blood alcohol content was 0.37 g/L. Three stimulants, pharmacologically related to amphetamines were detected: ETH (7.2 ng/mL), MTH ( Discussion ETH is an emergent illicit psychoactive substance that is an analogue of the prescription drug MTH (Ritalin ® ), both registered on the list of narcotics. Interestingly, ETH is produced as a metabolite from the co-ingestion of MTH and ethanol [1] . The hypothesis of a specific intake of ETH was retained because of its very high concentration compared to MTH. The therapeutic concentrations are between 5 and 80 ng/mL for MTH with a toxic level greater than 500 ng/mL, which can be extrapolated to ETH. Therefore we can exclude a toxic impregnation at the time of death. MODA, not classified as narcotic but with restricted prescription, is used in the treatment of excessive daytime sleepiness, and had also been used for working late and/or improved concentration [2] . The blood concentration is compatible with the expected concentration 2 hours after the administration at a dosage of 400 mg. A toxic concentration of MODA may be excluded at the time of death. The pharmacological activity of MODA can be described as comparable to that of MTH and ETH. These molecules potentiate their actions in case of combined consumptions, but the concentrations present are not in favour of cumulative impregnation intoxication. The cumulative concentrations of nordiazepam and oxazepam compatible with consumption of clorazepate are in the therapeutic level at the time of death. The measured blood concentration of amisulpride is much lower than the concentrations usually expected in therapy (100–320 ng/mL) and the activity of amisulpride at the time of sampling may be considered negligible. The concentration of sertraline is in the therapeutic range (10–150 ng/mL) and the measured blood concentration of lamotrigine is at least nontoxic. The combination of these treatments is not contraindicated. Conclusion The patient presented at the time of his death a blood impregnation of several stimulants: MODA in high therapeutic zone, traces of MTH, and ETH (narcotic without authorized therapeutic use) in nontoxic zone. The concentrations present are not in favour of a cumulative impregnation intoxication. MODA and MTH may be misused for their stimulant effects and can occur aggressive states or psychotic pathologies, which requires a reinforced monitoring. Uncontrolled consumption of these compounds can also induce cardiac pathologies as arrhythmias with lethal evolution that may constitute a toxicological hypothesis of death for this patient in absence of other cause of death.