Personalized Approach to Prediction and Prevention Clozapine-Induced QT Prolongation

Background: antipsychotics are widely used in psychiatry. Clozapine remains an indispensable antipsychotic due to its effectiveness. However, it has a wide range of undesirable effect, including an increased risk of QT prolongation, a potentially fatal complication that can lead to Torsade de Pointes (TdP) and sudden cardiac death. Objective: to systematize information for practicing psychiatrists about a personalized approach to the prevention of QT interval prolongation in patients with mental disorders when taking clozapine. Methods: a search for full-text articles published from 02/01/2014 to 02/01/2024 was carried out in PubMed, eLIBRARY.RU, Google Scholar. Results: this review analyzed and summarized the results of studies on the effect of clozapine on the QT interval, the role of risk factors and hereditary predisposition in the development of clozapine-induced prolongation of the QT interval and Torsade de Pointes in patients with mental disorders. The main mechanism of clozapine’s cardiotoxic effect is dose-dependent inhibition of potassium channels in the cardiomyocyte membrane. Clozapine is extensively metabolized in the liver, which may cause significant interindividual variability in its pharmacokinetics. A decrease in the rate of metabolism of clozapine may lead to an increase in its concentration in the blood, and thereby increase the risk of developing cardiotoxic adverse reactions. To reduce the risk of clozapine-induced QT prolongation, it is advisable to use predictive pharmacogenetic testing. Conclusion: Generalized data on the effect of clozapine on the duration of the QT interval and the risk of developing TdP in patients with mental disorders may be needed by psychiatrists when selecting the dose and duration of clozapine. Predictive pharmacogenetic testing can help reduce the incidence of potentially fatal ventricular arrhythmias.