The effect of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction

Abstract

Intracardiac conduction studies using His bundle electrography (HBE) were performed in 14 patients admitted to hospital following an overdosage of one of the tricyclic antidepressant drugs and in another 12 patients before and during administration of therapeutic doses of nortriptylline. Amongst the former group, 7 of 8 patients showed impaired distal intracardiac conduction (H-V interval) following overdosages of nortriptyline, imipramine or amitriptyline but none of the 6 patients with doxepin overdosage. The prolonged H-V interval had returned to normal at a repeat study 7 days later. In the therapeutic dose study, 5 of 12 patients showed an increase in the H-V interval by more than 10 msec during treatment with nortriptyline. Four of these 5 patients had plasma nortriptyline levels of over 200 ng/ml. Tricyclic antidepressant drugs show a quinidine-like effect in toxic, and in some patients, in therapeutic doses. This finding may having a bearing on the treatment of cardiac arrhythmias in patients following overdosage with these drugs and may provide a clue to the reported increase in the incidence of sudden deaths in 'cardiac patients' following therapeutic doses of such agents.