Recent developments in drug metabolism of relevance to psychiatrists

The discovery in 1977 of stable genetic differences (polymorphisms) in the oxidative metabolism of debrisoquine (P450 2D6) has led to an increasingly rapid growth in knowledge concerning the diversity of cytochrome P450 enzymes, their substrate-specific metabolism, and their interindividual variation. The current state of this knowledge for cytochromes P450 2D6, 2C19, 1A2, 3A3, and 2E1 is summarized, with a view toward their potential relevance to clinical psychopharmacology. To date, no prospective trials have tested the application of clinical tests of drug metabolism to treatment with psychotropics, and no guidelines have been formulated for such an application. The author reports preliminary findings from his studies of P450 2D6 phenotyping in elderly patients treated with nortriptyline and perphenazine. Research in this area may lead to earlier identification of patients at risk because of atypical drug metabolism. This might reduce drug-drug interactions, overmedication, or inadequate treatment.