safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2024-410safetyrisk-410Research ArticleГЛАВНАЯ ТЕМА: ТЕНЕВЫЕ СТОРОНЫ ФАРМАКОТЕРАПИИ: НЕЖЕЛАТЕЛЬНЫЕ РЕАКЦИИMAIN TOPIC: THE DARK SIDE OF PHARMACOTHERAPY: ADVERSE DRUG REACTIONSАнтипсихотик-индуцированное удлинение интервала QT и развитие Torsade de Pointes у пациентов с психическими расстройствами: обзорAntipsychotic-Induced QT Prolongation and Torsade de Pointes in Patients with Mental Disorders: A Reviewhttps://orcid.org/0000-0003-1874-9434НасыроваР. Ф.NasyrovaR. F.

Насырова Регина Фаритовна, д-р мед. наук

ул. Бехтерева, д. 3, Санкт-Петербург, 192019,

ул. Чапаевская, д. 89, г. Самара, 443099

Regina F. Nasyrova, Dr. Sci. (Med.)

3 Bekhterev St., St Petersburg 192019,

89 Chapaevskaya St., Samara 443016

regina_nmrcpn@mail.ruhttps://orcid.org/0009-0006-8999-9296КидяеваА. В.KidyaevaA. V.

Кидяева Алла Викторовна

ул. Бехтерева, д. 3, Санкт-Петербург, 1920193,

наб. реки Мойки, д. 126, Санкт-Петербург, 190121

Alla V. Kidyaeva

3 Bekhterev St., St Petersburg 192019,

126 Moika River Emb., St Petersburg 190121

alla.kid@mail.ruhttps://orcid.org/0000-0002-8493-0058ПетроваМ. М.PetrovaM. M.

Петрова Марина Михайловна, д-р мед. наук, профессор

ул. Партизана Железняка, д. 1, г. Красноярск, 660022

Marina M. Petrova, Dr. Sci. (Med.), Рrofessor

1 Partisan Zheleznyak St., Krasnoyarsk 660022

stk99@yandex.ruhttps://orcid.org/0000-0002-2840-837XШнайдерН. А.ShnayderN. A.

Шнайдер Наталья Алексеевна, д-р мед. наук, профессор

ул. Бехтерева, д. 3, Санкт-Петербург, 192019,

ул. Партизана Железняка, д. 1, г. Красноярск, 660022

Natalia А. Shnayder, Dr. Sci. (Med.), Professor

3 Bekhterev St., St Petersburg 192019,

1 Partisan Zheleznyak St., Krasnoyarsk 660022

naschnaider@yandex.ruИнститут персонализированной психиатрии и неврологии, Центр общего пользования, Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева; Международный центр образования и исследований в нейропсихиатрии, Самарский государственный медицинский университетРоссияInstitute of Personalized Psychiatry and Neurology, Shared Use Center, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; International Centre for Education and Research in Neuropsychiatry, Samara State Medical UniversityRussian FederationИнститут персонализированной психиатрии и неврологии, Центр общего пользования, Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева; Психиатрическая больница Святого Николая ЧудотворцаРоссияInstitute of Personalized Psychiatry and Neurology, Shared Use Center, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; St Nicholas Wonderworker Psychiatric HospitalRussian FederationЦентр коллективного пользования «Молекулярные и клеточные технологии», Красноярский государственный медицинский университет им. проф. В.Ф. Войно-ЯсенецкогоРоссияShared Core Facilities “Molecular and Cell Technologies”, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationИнститут персонализированной психиатрии и неврологии, Центр общего пользования, Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева; Центр коллективного пользования «Молекулярные и клеточные технологии», Красноярский государственный медицинский университет им. проф. В.Ф. Войно-ЯсенецкогоРоссияInstitute of Personalized Psychiatry and Neurology, Shared Use Center, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; Shared Core Facilities “Molecular and Cell Technologies”, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian Federation202416052024124380395Copyright © Насырова Р.Ф., Кидяева А.В., Петрова М.М., Шнайдер Н.А., 20242024Насырова Р.Ф., Кидяева А.В., Петрова М.М., Шнайдер Н.А.Nasyrova R.F., Kidyaeva A.V., Petrova M.M., Shnayder N.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/410ВВЕДЕНИЕ

ВВЕДЕНИЕ. Удлинение интервала QT является одной из наиболее значимых кардиотоксических нежелательных реакций, ассоциированных с применением антипсихотиков (АП), в связи с высоким риском развития жизнеугрожающих желудочковых аритмий, в частности пируэтной тахикардии (Тorsade de Рointes, TdP).

ЦЕЛЬ

ЦЕЛЬ. Систематизировать сведения о влиянии антипсихотиков на длительность интервала QT и риск развития пируэтной тахикардии у пациентов с психическими расстройствами и представить рекомендации по предотвращению их развития для практикующих психиатров и клинических фармакологов.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Поиск информации проводили в PubMed, eLIBRARY.RU, Google Scholar. В анализ включали полнотекстовые статьи, содержащие результаты плацебо-контролируемых исследований, перекрестных исследований, исследований типа «случай–контроль», систематических обзоров, метаанализов, Кокрейновских обзоров, опубликованных с 01.09.2013 по 30.09.2023. Основной механизм кардиотоксического действия АП заключается в ингибировании ими потенциал-зависимых ионных каналов мембраны кардиомиоцитов (прежде всего калиевых). Большинство АП 1-го поколения дозозависимо увеличивают длительность интервала QTc, наибольший риск наблюдался при применении тиоридазина, хлорпромазина и левомепромазина. Результаты проведенного анализа данных не позволили подтвердить гипотезу о том, что АП новых поколений имеют меньший риск удлинения интервала QTc по сравнению с АП 1-го поколения. Для АП 2-го и 3-го поколений в меньшей степени характерна связь между их сывороточной концентрацией и выраженностью удлинения интервала QTc. Все АП второго поколения удлиняют интервал QTc и повышают риск TdP, наибольший риск выявлен для клозапина и оланзапина. Представлено распределение АП по группам в зависимости от степени риска удлинения интервала QTc: группа низкого риска (арипипразол, луразидон, карипразин, палиперидон, зуклопентиксол), умеренного риска (кветиапин, перфеназин, флуфеназин, оланзапин, клотиапин, галоперидол) и высокого риска (хлорпромазин, промазин, клозапин, левомепромазин, зипрасидон). Обнаружено, что связь между АП-индуцированным удлинением интервала QTс и развитием TdP неоднозначна. В случае гомогенного действия АП на кардиомиоциты риск развития ТdP низкий, несмотря на значительное удлинение интервала QTс.

ВЫВОДЫ

ВЫВОДЫ. Обобщенные данные о влиянии АП на длительность интервала QT и риск развития TdP у пациентов с психическими расстройствами, предложенные рекомендации по снижению риска развития TdP могут быть востребованы психиатрами и клиническими фармакологами при подборе АП и способствовать минимизации вероятности возникновения потенциально фатальных АП-индуцированных аритмогенных кардиологических нежелательных реакций.

INTRODUCTION

INTRODUCTION. The high risk of life-threatening ventricular arrhythmias, particularly Torsade de Pointes (TdP), makes QT prolongation one of the most significant adverse drug reactions (ADRs) due to cardiotoxicity associated with antipsychotics (APs).

AIM

AIM. This study aimed to systematise information about AP effects on the QT interval duration and TdP risk in patients with mental disorders and to provide recommendations on preventive measures for practising psychiatrists and clinical pharmacologists.

DISCUSSION

DISCUSSION. The authors searched information in PubMed, eLIBRARY.RU, and Google Scholar. The analysis included full-text articles on the results of placebo-controlled studies, crossover studies, case–control studies, systematic reviews, meta-analyses, and Cochrane reviews published from 1 September 2013 to 30 September 2023. The main mechanism of AP cardiotoxicity is the inhibition of voltage-gated ion channels (primarily potassium channels) in the cardiomyocyte membrane. Most first-generation APs are associated with dose-dependent QTc prolongation; thioridazine, chlorpromazine, and levomepromazine pose the highest risk of QTc prolongation and TdP. The results of this review do not support the hypothesis of a lower risk of QTc prolongation with next-generation APs than with first-generation APs. The correlation between serum AP levels and QTc prolongation severity is less characteristic of secondand third-generation APs. However, all second-generation APs lengthen the QTc interval and increase the risk of TdP, with clozapine and olanzapine posing the highest risk. Depending on the risk of QTc prolongation, APs can be divided into 3 groups: low-risk products (aripiprazole, lurasidone, cariprazine, paliperidone, and zuclopentixol), moderate-risk products (quetiapine, perphenazine, fluphenazine, olanzapine, clothiapine, and haloperidol), and high-risk products (chlorpromazine, promazine, clozapine, levomepromazine, and ziprasidone). The relationship between AP-induced QTс prolongation and TdP is ambiguous. If an AP exerts a homogeneous effect on cardiomyocytes, the risk of TdP remains low despite significant QTс prolongation.

CONCLUSIONS

CONCLUSIONS. The summarised data on AP effects on QT interval duration and TdP risk in patients with mental disorders as well as the proposed recommendations for reducing TdP risk may be in demand by psychiatrists and clinical pharmacologists selecting AP and may help minimise the likelihood of potentially fatal AP-induced arrhythmogenic cardiac ADRs.

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The authors declare that there are no conflicts of interest present.