Severe proarrhythmic potential of risperidone compared to quetiapine in an experimental whole-heart model of proarrhythmia.

Abstract

In several case reports, proarrhythmic effects of antipsychotic drugs have been reported. The aim of the present study was to investigate if application of risperidone or quetiapine has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In 24 isolated rabbit hearts, risperidone (5 and 10 μM, n = 12) or quetiapine (5 and 10 μM, n = 12) was infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of risperidone as compared with baseline (5 μM: +29 ms, 10 μM: +35 ms, p < 0.01) accompanied by an increase of action potential duration. Administration of risperidone also significantly increased spatial dispersion of repolarization (5 μM: +16 ms, 4 μM: +19 ms; p < 0.05) as well as temporal dispersion of repolarization. Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 8 of 12 hearts and polymorphic ventricular tachycardia resembling torsade de pointes in 6 of 12 hearts (10 μM, 49 episodes). The results were compared with hearts treated with quetiapine (5 and 10 μM). Quetiapine led to an increase in QT interval (5 μM: +10 ms; 10 μM: +28 ms; p < 0.05) and a similar increase of APD90. However, treatment with quetiapine did not result in significant alterations of spatial and temporal dispersion of repolarization. No ventricular arrhythmias were observed in this group. In the present study, quetiapine demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, risperidone led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization.

• Authors: Gerrit Frommeyer, Henning von der Ahe, Benedict Brücher, Dirk G Dechering, Philipp S Lange, Florian Reinke, Kristina Wasmer, Julia Köbe, Christian Pott, Gerold Mönnig, Lars Eckardt
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 389 Issue 10 Pg. 1073-80 (Oct 2016) ISSN: 1432-1912 [Electronic] Germany
• PMID: 27405774 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antipsychotic Agents
• Quetiapine Fumarate
• Risperidone
• Potassium

Topics

• Action Potentials (drug effects)
• Animals
• Antipsychotic Agents (toxicity)
• Atrioventricular Block (physiopathology)
• Bradycardia (physiopathology)
• Cardiac Pacing, Artificial
• Electrocardiography
• Electrophysiologic Techniques, Cardiac
• Heart Rate (drug effects)
• Heart Ventricles (drug effects, metabolism, physiopathology)
• Isolated Heart Preparation
• Potassium (metabolism)
• Quetiapine Fumarate (toxicity)
• Rabbits
• Risk Assessment
• Risperidone (toxicity)
• Tachycardia, Ventricular (chemically induced, metabolism, physiopathology)
• Time Factors
• Torsades de Pointes (chemically induced, metabolism, physiopathology)