Antiarrhythmic effect of imipramine hydrochloride in patients with ventricular premature complexes without psychological depression.

A study was performed in cardiac patients without psychological depression to determine (1) the antiarrhythmic efficacy of imipramine, (2) its half-life of elimination and duration of action, and (3) the frequency of adverse effects. Twenty-two patients with 30 or more ventricular premature complexes/hour entered the protocol. A drug-free and a placebo day were followed by dosing with imipramine, 1 mg/kg per day, given in two divided doses. The dose was increased by 1 mg/kg per day every other day until ventricular premature complexes were suppressed by at least 80 percent, adverse drug effects were encountered or a total daily dose of 5 mg/kg per day was given. Each day a 24 hour continuous electrocardiogram was recorded to determine the frequency of ventricular premature complexes and heart rate. During the acute dose-ranging period, 18 patients (82 percent) had an antiarrhythmic effect from imipramine. Two patients received 5 mg/kg per day without any decrease in the frequency of ventricular premature complexes. The half-life of elimination of imipramine (parent compound) was 8.8 +/- 3.72 hours but its duration of action was much longer. Four patients (18 percent) had treatment discontinued because of troublesome adverse effects during a follow-up period of 19 +/- 8.8 months. It is concluded that imipramine is a potent antiarrhythmic drug with a long duration of action and relatively few major adverse effects.