Pharmacogenetics and drug metabolism of newer antidepressant agents.

Abstract

A wide variety of drugs are metabolized by the human cytochrome P450 system, 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 alleles that result in genetic polymorphism in the population. Both CYP2D6 and CYP2C gene families are polymorphic; both families are important in antidepressant metabolism. A number of polymorphisms result in dysfunctional or inactive enzymes. The clinical importance is highly dependent upon the patient's clinical state, coadministered drugs, therapeutic index, and the relative importance of the defective pathway in the total process of drug elimination. In addition, a number of drugs can also act as P450 enzyme inhibitors, which have the potential of causing drug interactions. In patient management, it is important to consider the fact that most antidepressants can also act as enzyme inhibitors. A number of adverse reactions resulting from coadministration of tricyclic antidepressants and SSRIs have been described. Such drug interactions can be minimized or avoided by following simple clinical logic.