Responses to tyramine and norepinephrine after imipramine and trazodone

Trazodone is a new antidepressive with properties which differ from those of tricyclics. In animals, trazodone seems to be devoid of catecholamine potentiating action, which is thought to be responsible for the cardiotoxicity of this tricyclic. Our study was undertaken to determine the cardiovascular effects of trazodone in man, as indicated by responses to tyramine and norepinephrine. Six normal subjects received either imipramine (25 mg) 3 times a day or trazodone (50 mg) 3 times a day according to a double‐blind randomized cross‐over protocol with a placebo washout period. Each subject was tested on placebo after the first dose and after 1 wk of each drug. The responsiveness of blood pressure to tyramine differed after placebo and imipramine but not after placebo and trazodone. The responsiveness of blood pressure to norepinephrine was increased by imipramine and seemed to be depressed by trazodone after single doses and after 7 days of treatment. Except for one case of sinus bradycardia during norepinephrine infusion, no major side effects were noted during the study. Trazodone seems to have no effect on the blood pressure response to tyramine and presumably does not affect the uptake of tyramine into the adrenergic neuron, while decreased sensitivity to norepinephrine was indicated by the blood pressure response.