In several case reports proarrhythmic effects of
citalopram and
escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of
citalopram,
escitalopram or
haloperidol provokes polymorphic
ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of
citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced
potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic
ventricular tachycardia (pVT). Application of
escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with
haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes).
Citalopram and
escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast,
haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of
citalopram or
escitalopram. These results imply that application of
citalopram or
escitalopram is not as proarrhythmic as some case reports might suggest while
haloperidol is torsadogenic.