Introduction: Antipsychotic drugs cause prolongation in the QTc interval and may cause sudden cardiac death in patients. The reason for this prolongation in QTc interval is that cardiac repolarisation is made more difficult due to the blockade of potassium channels. Therefore, antipsychotic medications predispose patients to torsades de pointes and ventricular tachychardia. The purpose of this study was to reveal the effects of metoprolol and diltiazem on drug induced (ziprasidone) prolonged QTc (QT correct) interval.
Materials-methods: The experiments performed in this study were carried out according to the rules in the Guide for the Care and Use of Laboratory Animals adopted by the National Institutes of Health (U.S.A) and received consent from Ege University Animal Ethics Committee.
In this study 18 Sprague-Dawley adult male rats were used. Before administration of the anti-psychotic under anesthesia (ketamine (40 mg/kg) and xylazine (4 mg/kg) intraperitoneally (IP)), an ECG was taken in derivation (D) I and the normal QTc interval was determined. To calculate the QTc interval, Bazett's formula was used. The rats were divided into 3 groups (n=6). For the first group, 3 mg/kg ziprasidone and saline, for the second group, 3 mg/kg ziprasidone and 1 mg/kg metoprolol and for the third group, 3 mg/kg ziprasidone and 2 mg/kg diltiazem were administered intraperitoneally. Two hours later, under anesthesia, the QTc interval was calculated by taking the ECG in derivation I.
Results: In the first group of rats, given ziprasidone and saline the QTc interval (0.161±0.01 s) was significantly (p<0.05) prolonged compared to the QTc interval (0.125±0.009 s) before the drug administration. In the second group of rats, administered ziprasidone and metoprolol, the QTc interval (0.123±0.009 s) was significantly (p<0.05) shortener than that of the group given ziprasidone and saline (the first group, QTc interval = 0.161±0.01 s) In the third group of rats, injected with ziprasidone and diltiazem, the QTc interval (0.125±0.004 s) was significantly (p<0.05) shorter than that of the group given ziprasidone and saline (the first group, QTc interval = 0.161±0.01 s).
Discussion: High dose ziprasidone causes prolongation in the QTc interval. Metoprolol and diltiazem prevent ziprasidone induced elongation of the QTc interval. The prophylactic use of these drugs may be an option for reducing the risk for ventricular arrhythmias and sudden cardiac death in patients taking antipsychotics.