Antidepressants and drug-metabolizing enzymes--expert group report.
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.
Meyer
U A
UA
University of Basel, Department of Pharmacology, Switzerland.
Amrein
R
R
Balant
L P
LP
Bertilsson
L
L
Eichelbaum
M
M
Guentert
T W
TW
Henauer
S
S
Jackson
P
P
Laux
G
G
Mikkelsen
H
H
Peck
C
C
Pollock
B G
BG
Priest
R
R
Sjöqvist
F
F
Delini-Stula
A
A
D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases; D002986:Clinical Trials as Topic; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy / Q000201:enzymology* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004798:Enzymes / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008657:Metabolic Clearance Rate / Q000502:physiology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics
D000928:Antidepressive Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004798:Enzymes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6