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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.

Clonidine, an alpha-2-adrenergic agonist, significantly reduces opiate withdrawal. Fifteen heavy smokers abstained from cigarettes on three separate occasions and received instead clonidine, placebo, or the benzodiazepine alprazolam. Clonidine and alprazolam diminished withdrawal symptoms. The two drugs suppressed anxiety, tension, irritability, and restlessness equally but clonidine had a greater effect than alprazolam on cigarette craving. These observations suggest that noradrenergic activity is a common feature in the pathophysiology of withdrawal and that a special relationship exists between central noradrenergic activity and craving.

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