ANTIDEPRESSANTS AND DRUG-METABOLIZING-ENZYMES - EXPERT GROUP-REPORT

Antidepressant drugs are extensively metabolized. Consequently, the bi otransformation pattern of antidepressants has an important influence on their clinical properties, i.e., pharmacokinetics, toxicity, drug-d rug interactions, side-effect profile and last but not least therapeut ic efficacy. It, was against this background that a multidisciplinary group of experts discussed the clinical relevance of the rapidly incre asing body of knowledge of antidepressant-metabolizing enzymes. The va riability of the response of a given individual to an antidepressant i s determined genetically and by the environment. Genetic polymorphism of drug-metabolizing enzymes and inhibition by other substrates may af fect the enzymatic biotransformation of antidepressants. In vitro assa y techniques allow an estimation of the potential variability in clini cal response to antidepressants and a reasonable prediction of the dru g-drug interaction patterns. The results of in vitro tests should ther efore be considered early in the development of an antidepressant as a background for designing clinical studies (treatment schedules and do sing). Physicians should have an understanding of the relevance of gen etic polymorphism for clinical practice. Education is needed in order to fill the existing gaps in knowledge about antidepressant-enzyme int eractions and their application in daily treatment practice. The infor mation on potential drug interactions determined by genetic polymorphi sm and based on studies with enzymes should be increasingly contained in drug compendia.