ECG effects of comparable plasma concentrations of desipramine and amitriptyline

To compare the electrocardiographic effects of therapeutic doses of desipramine and amitriptyline, weekly electrocardiograms (ECGs) were obtained from 46 depressed outpatients treated blindly for 3 weeks to a maximum of 200 mg/day. There was no difference in mean weekly plasma tricyclic antidepressant levels achieved for the two drugs. Compared to baseline measures, treatment with both drugs was associated with an increase in heart rate and a reduction in T wave amplitude, whereas prolongation of the QRS and QTc intervals was significant only for desipramine patients. Comparisons between drugs revealed a greater prolongation of QRS interval duration with desipramine treatment. Changes in ECG measures were not correlated with plasma tricyclic antidepressant levels. The absence of QRS interval prolongation among amitriptyline patients is additional evidence for the importance of distinguishing between the ECG effects of therapeutic and toxic doses of the tricyclic antidepressant.