Acute cardiac effects of fluvoxamine and other antidepressants in conscious rabbits

The effects of continuous infusion of amitriptyline (0.35 mg/kg/min), mianserin (0.70 mg/kg/min) or fluvoxamine (0.70 mg/kg/min) were studied on electrocardiogram (ECG), heart contractility and temperature in conscious rabbits. Lethal doses for amitriptyline (median 13.6 mg/kg) were much lower than for mianserin (median 56.0 mg/kg) or fluvoxamine (median 59.5 mg/kg). Amitriptyline induced severe arrhythmias and ECG disturbances at relatively low doses. Mianserin induced arrhythmias and ECG disturbances at higher doses, while arrhythmias were infrequently seen with fluvoxamine. ECG disturbances were observed at fluvoxamine doses approaching lethality. Amitriptyline very much lowered contractility as assessed by LVdP/dt. With fluvoxamine a decrease in LVdP/dt was only observed at moderate doses while at nearly lethal doses neither fluvoxamine nor mianserin induced a decrease in LVdP/dt. Fluvoxamine raised body temperature significantly. Fluvoxamine seems, at least in this animal model, a drug which induces far fewer cardiac disturbances than amitriptyline and even fewer than mianserin. It is concluded that fluvoxamine is relatively free from cardiotoxicity.