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Topicality. Increase in the use of antipsychotics and antidepressants in many countries led to augmentation of acute poisoning amount with lethal cases. Among them, the main part is combined poisoning, including combination with other medicines, which significantly complicates the conduction of chemical-toxicological analysis.Aim. To conduct the analytical review of side effects and lethal cases of acute poisoning by antipsychotics and antidepressants, including combination with other medicines.Materials and methods. Analysis of websites and online literature sources such as: ehealthme.com, patientsville.com, Academia.edu, PubMed, ResearchGate, Scopus etc.Results and discussion. According to the results of sources analysis, in the period from 2013 to 2018, there were registered 5094 cases of side effects and 56 lethal poisonings with the use of the most commonly used antipsychotics of phenothiazine derivatives. Also 6013 cases of side effects and 675 lethal poisonings were registered with the use of tricyclic antidepressants. The main side effects and causes of fatalities have been identified. The combined use of antipsychotics and antidepressants and its simultaneous application with medicines from other pharmacological groups, increases the risk of poisoning. It greatly complicates the chemical and toxicological searches to determine the cause of poisoning.Conclusions. The conducted research determined the factors of deterioration the toxicological situation recently which has developed with the use of antipsychotics and antidepressants and substantiated feasibility of the development of methods of chemical-toxicological analysis for drugs that caused fatal poisoning.