Drug-metabolizing enzymes and therapeutic drug monitoring in psychiatry.

The multiplicity of the drug-metabolizing cytochrome P450 system was discovered 20 years ago. During the past 10 years the complementary DNAs of the most important P450 enzymes have been cloned and sequenced, and much has been learned about their substrate specificities, selective inhibitors, and functional characteristics. Cytochrome P4501A2 (CYP1A2), CYP2C19, CYP2D6, and CYP3A4 are the most important P450s catalyzing the biotransformation of psychotropic drugs. Assessment of the activity of individual P450 enzymes makes it possible to forecast an appropriate initial dose in a patient. At present, this strategy can be recommended only for CYP2D6 before treatment with tricyclic antidepressants and certain neuroleptics. Important drug-drug interactions can be predicted if two substrates or a substrate and an inhibitor of a particular P450 are co-administered. Therapeutic drug monitoring is of invaluable help in discovering and handling this type of interaction.