Depressed patients develop symptomatic and fatal ischemic heart disease at a higher rate than nondepressed patients, even after studies are controlled for known cardiovascular risk factors. Changes in sympathetic and parasympathetic tone appear to make depressed patients more vulnerable to ventricular fibrillation. Tricyclic antidepressants share the electrophysiologic profile of type 1A antiarrhythmic compounds and therefore may carry a risk of increased mortality when given to patients with ischemic heart disease. Serotonin reuptake inhibitors have shown no antiarrhythmic effect in depressed patients with serious cardiovascular disease, but studies to date have been small and short-term.