Some Drug-Drug Interactions Involving Psychotropic Agents

Abstract

The idiosyncracies of drug response and drug-drug interaction are often secondary to the idiosyncracies of individual organ systems because they are affected by such factors as age, youth, disease, or genetically transmitted characteristics. With the multiplicity of psychopharmacologic agents now available, and with the tendencies of many psychiatrists toward prescription of poly-pharmacy, the frequency and variety of psychotropic drug interactions are increasing faster than our ability to discover and adequately analyze the causative components. Our knowledge of the genetic factors influencing these activities is particularly deficient, and the necessary body of animal data upon which to base careful human studies has not yet been suitably developed. Reports of unanticipated psychotropic drug-drug interactions in which genetic factors appear to figure significantly are few and tentative. Some cases of genetically influenced responses involving singly administered agents interacting with organ systems have been reported (Kalow, 1971). Well documented instances of one drug altering the activity of another as a result of genetic factors, such as the inhibition of diphenylhydantoin metabolism by iproniazid in slow acetylators (Kutt and McDowell, 1968) are particularly scarce. Rather than attempt a compendium of annecdotal reports of such cases here, we will devote this brief chapter to an outline of some of the broader mechanisms which we can state with some assurance are fairly consistent components in the interactivity of multiple drugs within living organisms. As further information concerning the role of genetics in these processes is developed in the future, it will probably have to be done with reference to the patterns with which we have thus far seen drug-drug interactions occur when they are influenced by advanced age, disease or trauma to effected organs and tissues, or matters of biochemical compatibility. The following information is presented, therefore, as a construct of both established and theoretically possible occurrences.

This work was supported in part by a grant from the Veterans Administration.