Antidepressants, stress and cardiotoxicity

Various types of cardiomyopathies have been induced in rats, which were then subjected to a standard noise stress. This resulted in immediate death due to ventricular fibrillation in some 2 per cent of the animals. Pretreatment with tricyclic antidepressants increased this mortality dramatically to 70–90 per cent, although concomitant administration of propranolol and various anxiolytic drugs protected against this effect to varying degrees. Further experiments, using cold and exercise stressors, produced similar results, although the noise stress was by far the most lethal. Propranolol protected the animals against the effects of cold and exercise stressors but diazepam did not. Experiments with the second generation antidepressants, trazadone and nomifensine, were completely negative and it would appear that, in the context of this animal model, these drugs possess no cardiotoxic effects. There would seem to be a direct parallel between these animal experiments and tricyclic cardiotoxicity in man, the depressive illness itself or its precipitating causes constituting the stress factor. Our results suggest that the second generation antidepressants would appear to be safer from this point of view.