PHARMACOGENETICS AND DRUG-METABOLISM OF NEWER ANTIDEPRESSANT AGENTS

A wide variety of drugs are metabolized by the human cytochrome P450 s ystem, including antidepressants such as tricyclic antidepressants and serotonin selective reuptake inhibitors (SSRIs). Each P450 isoenzyme is the product of a separate gene; a number of genes have multiple all eles that result in genetic polymorphism in the population. Both CYP2D 6 and CYP2C gene families are polymorphic; both families are important in antidepressant metabolism. A number of polymorphisms results in dy sfunctional or inactive enzymes. The clinical importance is highly dep endent upon the patient's clinical state, coadministered drugs, therap eutic index, and the relative importance of the defective pathway in t he total process of drug elimination. In addition, a number of drugs c an also act as P450 enzyme inhibitors, which have the potential of cau sing drug interactions. In patient management, it is important to cons ider the fact that most antidepressants can also act as enzyme inhibit ors. A number of adverse reactions resulting from coadministration of tricyclic antidepressants and SSRIs have been described. Such drug int eractions can be minimized or avoided by following simple clinical log ic.