Acta Psychiatr zyxwvutsrqponmlkj Scand 1996: 93: 71-79 Printed in UK zyxwvutsrqponm - all rights reserved Copyright zyxw 0 Munksgaard 1996 zy ACTA PSYCHIATRICA SCANDINAVICA ISSN zyxw 000149oX zyx Review article Antidepressants and drug-me t abolizing enzymes - expert group report Meyer UA, Amrein R, Balant LP, Bertilsson L, Eichelbaum M, Guentert TW, Henauer S, Jackson P, Laux G, Mikkelsen H, Peck C, Pollock BG, Priest R, Sjoqvist F, Delini-Stula A. Antidepressants and drug-metabolizing enzymes - expert group report. Acta Psychiatr Scand 1996: 93: 71-79. 0 Munksgaard 1996. Antidepressant drugs are extensively metabolized. Consequently, the biotransformation pattern of antidepressants has an important influence on their clinical properties, i.e., pharmacokinetics, toxicity, drug-drug interactions, side-effect profile and last but not least therapeutic efficacy. It was against this background that a multidisciplinary group of experts discussed the clinical relevance of the rapidly increasing body of knowledge of antidepressant-metabolizing enzymes. The variability of the response of a given individual to an antidepressant is determined genetically and by the environment. Genetic polymorphism of drug- metabolizing enzymes and inhibition by other substrates may affect the enzymatic biotransformation of antidepressants. In vitro assay techniques allow an estimation of the potential variability in clinical response to antidepressants and a reasonable prediction of the drug-drug interaction patterns. The results of in vitro tests should therefore be considered early in the development of an antidepressant as a background for designing clinical studies (treatment schedules and dosing). Physicians should have an understanding of the relevance of genetic polymorphism for clinical practice. Education is needed in order to fill the existing gaps in knowledge about antidepressant-enzyme interactions and their application in daily treatment practice. The information on potential drug interactions determined by genetic polymorphism and based on studies with enzymes should be increasingly contained in drug compendia. Antidepressant agents are extensively metabolized by the cytochrome P450 enzyme family. Recently, great progress has been made in the understand- ing of drug-metabolizing enzymes. It was against this background that a multidisciplinary group of experts discussed the clinical relevance of this increasing body of knowledge. The aim was to arrive at a consensus view about the importance of the interaction of antidepressants with drug- metabolizing enzymes for clinical practice and to make it available to the medical profession in order to improve patient care through better knowledge of variability in metabolism and response to antide- zyxwv U. A. Meyer', R. Amrein', L. P. Balanf, L. Bettilsson4, M. Eichelbau~n~, T. W. Guented, S. Henauef, P. Jackson', G. Laux', H. Mikkelsen', C. Peck', B. G. Pollock", R. Priest", F. Sjoqvist", A. Delini-Stula' 'Biozentrum. University of Basel. Department of Pharmacology, Basel. *Hoffmann- La Roche AG. Basel. 'Clinical Research Unit, Psychiatric University Institutions. Geneva, Switzerland, 4Karolinska Institute, Department of Clinical Pharmacology, Huddinge University Hospital, Sweden, 5Dr. Margarete Fischer-Bosch- lnstitut fur Klinische Pharmakologie, Stuttgart, Germany, 6PharmaPart. Zurich, Switzerland, 7University Department of Medicine and Pharmacology, Section of Pharmacology and Therapeutics, Royal Hampshire Hospital, Sheffield, United Kingdom, 'Psychiatrische Universitatsklinik. Bonn, Germany, 'Center of Bio- Pharmacological Sciences, Clinical Pharmacology, Leiden. the Netherlands, 'Western Psychiatric Institute & Clinic, University of Pittsburgh, Pennsylvania, USA, "St. Mary Hospital, Medical School, London, United Kingdom, "Huddinge University Hospital, Department of Clinical Pharmacology, Sweden Key words: antidepressant drug; pharmacogenetics; drug-metabolizing enzyme Alexandra Delini-Stula, Hoffmann-La Roche AG, Postfach. CH-4002 Basel, Switzerland Accepted for publication July 9. 1995 pressants, side effects and drug-drug interactions. Guidelines of this type may also help the pharma- ceutical industry and regulatory authorities to decide on the design of rational programs for the development of new drugs. Although this confer- ence focused on antidepressant agents, many of the conclusions are equally valid for other classes of therapeutic agents, such as neuroleptics. Scope Discussion centered on what was known about genetic polymorphisms and their effects on metabol- 71