Персонализированный подход к прогнозированию и профилактике клозапин-индуцированного удлинения интервала QT

Обоснование: антипсихотики широко используются в психиатрии. Клозапин остается незаменимым антипсихотиком в силу своей эффективности. Однако он обладает достаточно широким спектром нежелательных эффектов, в том числе повышает риск развития удлинения интервала QT — потенциально фатального осложнения, которое может привести к развитию пируэтной желудочковой тахикардии Тorsade de Рointes (TdP) и внезапной сердечной смерти. Цель: систематизировать информацию для практикующих психиатров о персонализированном подходе к профилактике удлинения интервала QT у пациентов с психическими расстройствами при приеме клозапина. Методы: поиск полнотекстовых статей, опубликованных с 01.02.2014 по 01.02.2024, проведен в PubMed, eLIBRARY.RU, Google Scholar. Результаты: в обзоре проанализированы и обобщены результаты исследований, посвященных влиянию клозапина на интервал QT, роли факторов риска и наследственной предрасположенности в развитии клозапин-индуцированного удлинения интервала QT и тахикардии Тorsade de Рointes у пациентов с психическими расстройствами. Основной механизм кардиотоксического действия клозапина заключается в дозозависимом ингибировании калиевых каналов мембраны кардиомиоцитов. Клозапин активно метаболизируется в печени, что может вызывать значительную индивидуальную вариабельность его фармакокинетики. Снижение скорости метаболизма клозапина может привести к росту его концентрации в крови и тем самым повысить риск развития кардиотоксических эффектов. Для снижения риска развития клозапин-индуцированного удлинения интервала QT целесообразно использовать предиктивное фармакогенетическое тестирование. Заключение: обобщенные данные о влиянии клозапина на длительность интервала QT, риск развития TdP у пациентов с психическими расстройствами могут быть востребованы психиатрами при подборе дозы и длительности приема клозапина. Предиктивное фармакогенетическое тестирование может способствовать снижению вероятности возникновения потенциально фатальных желудочковых нарушений ритма.

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