[Clozapine intoxication: theoretical aspects and forensic-medical examination ]

This literature review is focused on diagnostics of acute clozapine intoxication with the fatal outcome. According to the Russian authors, clozapine intoxication ranks first in the structure of criminal poisoning and accounted for 99.7% of all the cases that occurred in Moscow during the period from 2003 to 2006. Toximetric investigations of clinical manifestations of clozapine intoxication revealed that the threshold clozapine concentration in blood is 0.12 ± 0.06 mg/I, the critical and lethal concentrations are 1.01 ± 0.2 mg/I and 3.5 ± 1.5 mg/I respectively. Autopsy on corpses of the victims of clozapine intoxication showed that most clozapine-induced pathological changes have a non-specific character (including largely circulatory disorders and dystrophic changes in parenchymatous organs). Clozapine poisoning is associated with the lengthening of QT-interval on ECG; at the values in excess of 500 ms, the risk of severe arrhythmia and sudden death significantly increases. Clozapine intake may lead to the development of potentially fatal myocarditis (the so-called clozapine-associated eosinophilic myocardium) in somatically healthy subjects. Foreign researchers report the possibility of a post-mortem increase of blood clozapine content compared with its antemortem level. They also showed that simultaneous use of substances stimulating activity of cytochrome P-450 enzymes (ethyl alcohol, finlepsin, fenitrin, nicotine) and clozapine accelerates metabolism and thereby reduces clozapine concentration in blood. It is concluded that comprehensive investigations of clozapine intoxication are needed taking into consideration pathomorphological changes induced by this agent, its potential interaction with other factors influencing human body, and the results of forensic chemical expertise of the fatal cases.