The safety of tricyclic antidepressants in cardiac patients. Risk-benefit reconsidered

IN 1977, we first reported the antiarrhythmic effect of imipramine hydrochloride.1Prior to that time, physicians generally believed that the tricyclic antidepressants (TCAs) caused arrhythmia. That belief stemmed from the propensity of overdoses of these drugs to provoke arrhythmias.2However, it subsequently became apparent, both from our studies3-6and the work of others,7that at plasma concentrations therapeutic for depression,8TCAs suppress arrhythmias, and their cardiac effects closely resemble those of class I antiarrhythmic drugs.9,10Until recently, it was our belief that depressed patients with preexisting arrhythmias would benefit from the antiarrhythmic effect of TCAs.11,12Unfortunately, recent studies indicate that this opinion may need to be revised. Ventricular premature depolarizations (VPDs) are a well-documented risk factor for sudden death after myocardial infarction (MI)13,14and the assumption had been that drugs that suppress VPDs would reduce this associated mortality. However, in 1983, Furberg