A comparative pharmacodynamic study of the arrhythmogenicity of antidepressants, fluvoxamine and imipramine, in guinea pigs

Among several classes of antidepressants, tricyclic antidepressants are kno wn to prolong QTe intervals (QT interval corrected by heart rate) in electr ocardiograms, while selective serotonin uptake inhibitors (SSRI) are consid ered to be devoid of arrhythmogenicity, In this study, H e aimed to compare the arrhythmogenic potencies of imipramine (IMI), a typical tricyclic anti depressant, and fluvoxamine (FLV), an SSRI, at therapeutic and supratherape utic concentrations using guinea pigs in vivo. Guinea pigs were anesthetized, and IMI (10 and 20 mg/kg/h) or FLV (20 mg/kg /h) was intravenously administered for 90 minutes to obtain the time-course s of drug concentrations in plasma and thr changes in thp QTc intervals dur ing and after the drug administration, IMI induced distinct QTe prolongation in a dose-dependent manner, while FLV prolonged QTe intervals only; slightly, A pharmacokinetic-pharmacodynamic analysis revealed that the potency for QTc prolongation of IMI was 1.7-fold higher than that of FLV Taking the therapeutic concentration into account, the clinical risk of FLV for QTc prolongation was suggested to be 5-fold l ower than that of IMI, Therefore, this SSRI agent was suggested to be safer than the tricyclic antidepressant for patients with cardiac risk factors, including arrhythmia, or for those taking other arrhythmogenic drugs concom itantly.