The electrocardiographic effects of imipramine hydrochloride at therapeutic plasma concentrations were determined in 44 depressed patients during a 6-week clinical outcome study of depression. During each week of the protocol, i.e., 2 weeks of control and 4 weeks of drug treatment, a standard 12-lead ECG, high-speed, high-fidelity ECG tracings, and a 24-hour continuous ECG recording were obtained. PR, QRS, and QTc intervals, T-wave amplitude, heart rate and frequency of ventricular premature depolarizations (VPDs) were measured. The plasma concentration of imipramine and desmethylimipramine was measured three times a week. Imipramine prolonged the PR (p less than 0.001), QRS (p less than 0.001) and QTc (p less than 0.001) intervals, increased the heart rate (p less than 0.001) and lowered T-wave amplitude (p less than 0.05) during the 4 weeks of treatment. No patient developed high-grade atrioventricular block or severe intraventricular conduction abnormalities. In addition, imipramine had a potent antiarrhythmic action in patients who were recovering from depression. Ten of 11 patients who had more than 10 VPDs/hour had 90% or greater arrhythmia suppression during antidepressant treatment with imipramine at plasma concentrations ranging from 100--302 ng/ml.

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A review of the abundant literature concerning the distinction between delusional and non-delusional depressions, especially of the work of Aubrey Lewis, reveals that before the introduction of specific therapies most in-patients with major depressive illness eventually recovered; the small percentage who did not almost all came from the delusional group. The dichotomy lost its clinical significance after the introduction of ECT, as both groups were equally responsive. However, accumulating evidence indicates that unipolar delusional depressives are significantly less responsive to tricyclic anti-depressant therapy than non-delusional depressives. The presence or absence of delusional thinking should be considered as a significant criterion in the classification of depressive disorders, and the presence or absence of delusional thinking should influence the choice of treatment for severely depressed patients.