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Antipsychotikainduzierte QT-Verlängerung

Lengthening of QT interval by antipsychotic drugs

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Zusammenfassung

Antipsychotika gehören zu den Medikamenten, die eine Verzögerung der myokardialen Erregungsrückbildung und damit eine Verlängerung des QT-Intervalls im Oberflächen-EKG bewirken können. In Zusammenhang hiermit kann es im Einzelfall, bei prädisponierten Patienten, zu einer abnormen, überschießenden QT-Verlängerung und schwerwiegenden ventrikulären Herzrhythmusstörungen vom Typ der „torsade de pointes“ (TdP) kommen. Meist ist ein Pharmakon nicht die einzige Ursache, sondern weitere Faktoren sind an der Entstehung der resultierenden Arrhythmien beteiligt. Hierzu gehören z. B. eine Serumhypokaliämie, Bradykardien, Medikamentenkombinationen, Medikamentenüberdosierungen oder Intoxikationen, beispielsweise durch Metabolisierungs- oder Ausscheidungsstörung. TdP können auch auftreten, wenn lediglich eine schwerwiegende Hypokaliämie und/oder ausgeprägte Bradykardie vorliegen. Eine Verzögerung der myokardialen Erregungsrückbildung lässt sich unter experimentellen Bedingungen bei fast allen Antipsychotika nachweisen. Das Ausmaß der QT-Verlängerung im Oberflächen-EKG ist unterschiedlich. Gut belegt ist der Zusammenhang zwischen überschießender QT-Verlängerung und TdP für Thioridazin. Fallberichte liegen auch für andere Antipsychotika vor. Auch wenn es sich bei TdP um eine seltene Nebenwirkung von Antipsychotika handelt, sollten die Charakteristika dieser besonderen unerwünschten Arzneimittelwirkung demjenigen bekannt sein, der Antipsychotika verschreibt. Es gilt, die Risikofaktoren für das Auftreten solcher Effekte zu erkennen und vor und während Therapie mit Antipsychotika zu kontrollieren.

Summary

Prolongation of myocardial repolarisation, i.e. lengthening of the QT interval on surface electrocardiogram, has been recognised as a side effect of many drugs, including antipsychotics. In predisposed individuals, abnormal excessive QT prolongation and severe ventricular arrhythmias (the ventricular tachycardia type ‘torsade de pointes’, or TdP) may occur. In almost all cases, additional factors are present that increase the propensity of patients to develop TdP, such as serum hypokalemia, the combination of drugs prolonging repolarisation, overdosing, intoxication, and factors interfering with drug metabolism and excretion. Serum hypokalemia and/or bradycardia may induce TdP alone, in the absence of drugs prolonging the QT interval. Experimental studies demonstrate that prolongation of myocardial repolarisation is a class effect of neuroleptics. Clinically, the extent to which individual drugs prolong the QT interval varies. Among the antipsychotics, thioridazine has the greatest propensity to induce abnormal QT prolongations and TdP. Case reports of TdP with other antipsychotics have been published. Physicians prescribing phyicians these drugs must be aware that they can induce proarrhythmia in individual cases. They should also be aware of the circumstances which are necessary for abnormal QT prolongation and TdP to develop. Patients should be monitored with regard to these risk factors before and during drug treatment.

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  1. Medizinische Klinik mit Schwerpunkt Kardiologie, Campus Virchow-Klinikum, Charité — Universitätsmedizin Berlin

    W. Haverkamp

  2. Zentralinstitut für Seelische Gesundheit, Mannheim

    M. Deuschle

  3. Medizinsche Klinik mit Schwerpunkt Kardiologie, Campus Virchow-Klinikum, Charité — Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    W. Haverkamp

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Correspondence to W. Haverkamp.

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Haverkamp, W., Deuschle, M. Antipsychotikainduzierte QT-Verlängerung. Nervenarzt 77, 276–288 (2006). https://doi.org/10.1007/s00115-005-1966-x

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