Cardiovascular Effects of Single Doses of the Antidepressants Amitriptyline and Lofepramine in Healthy Subjects*

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Abstract
In a placebo-controlled double blind study, single oral doses of lofepramine (140 mg and 210 mg) and amitriptyline (100 mg and 150 mg) were given to 5 healthy volunteers. Heart rate, blood pressure, systolic time intervals, and electrical impedance cardiogram were recorded in supine and upright position for 8 hours after drug administration. In addition, plasma drug concentrations were measured simultaneously. Amitriptyline caused a more pronounced increase in heart rate, especially under orthostatic stress, than did lofepramine. Both drugs reduced total peripheral resistance; amitriptyline's effect was greater. A rise in blood pressure (supine position) and shortening of the electromechanical systole under lofepramine indicated an improvement of cardiac performance. In contrast amitriptyline, particularly, in the upright position, lowered blood pressure and lengthened electromechanical systole. Since both drugs have a comparable antidepressant activity, lofepramine is suggested to induce fewer untoward cardiovascular reactions than amitriptyline.

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