Chronic chlorpromazine administration: Some pharmacological and psychological effects in man

Abstract

This study was undertaken to determine whether there were changes in the pharmacological profile of chlorpromazine when it was given over a long period of time and in view of these findings to examine claims that chlorpromazine is clinically useful as an antidepressant. Fifteen patients with chronic mental illness were given infusions of epinephrine, norepinephrine, histamine, and yohimbine before and at 1, 10, 30, and 90 days during a course of chlorpromazine therapy. Psychological measurements by observers unaware of drugs given indicated that the anxiety‐arousing effects of epinephrine were reduced by chlorpromazine but that the anxiety‐like effects of yohimbine were potentiated. Histamine and norepinephrine had no significant psychological effect. Treatment with chlorpromazine reduced manifestations of mental illness. Base‐line blood pressure was reduced Significantly early in chlorpromazine therapy but only slightly later on. The systolic pressor effects of epinephrine were reduced by chlorpromazine but to a lesser extent late in the 90 day period. Norepinephrine systolic blood pressure effects were not Significantly altered by chlorpromazine. The cardiovascular effects of histamine were potentiated by chlorpromazine throughout as were the cardiovascular effects of yohimbine. In a parallel dog study chlorpromazine augmented norepinephrine pressor effects. It is concluded that, in view of its tendency to potentiate yohimbine and norepinephrine, chlorpromazine has some characteristics similar to those of the antidepressant drug imipramine. These results are discussed in relation to findings that chlorpromazine and imipramine alter storage and release of catecholamines