Pharmacogenetics of Antidepressant Drug Metabolism and Its Clinical Implications

Abstract:

It is frequently observed in clinical practice that there is a certain variability in clinical efficacy and in the occurrence of side effects in patients treated with the same dose of a drug. This inter-individual variability also in the response to antidepressant drugs can be partly attributed to differences in plasma concentrations of the drug and/or its metabolites. One of the major factors influencing drug elimination and, thus, plasma concentration is the activity of the cytochrome P450 (CYP) enzymes. Every CYP enzyme is encoded by a separate gene; thus, each represents a monogenetic trait. A large number of these enzymes have been described and classified into 18 families. At present, CYP2D6, CYP2C19, CYP2C9, CYP1A2, and CYP3A4 have been shown to be the most important enzymes in psychopharmacology because of their implication in the metabolism of several psychotropic drugs, including antidepressants. Individuals with low enzyme activity are referred as slow or poor metabolizers, while the others are rapid or extensive metabolizers. Besides the genetic determination, environmental factors and concomitant treatment also may modify the activity of these enzymes. Another aspect is the ability of certain antidepressant drugs to inhibit the activity of specific CYP enzymes. The clinical relevance of this fact is that this inhibition may lead to higher than expected plasma concentrations of the drug and also to drug interaction with other medications metabolized by the same specific enzyme. In this review the present knowledge on the CYP enzyme-mediated metabolism of the specific antidepressant drugs and the possible clinical implications are summed up. The knowledge of the possible influence of CYP enzymes on the therapeutic efficacy of antidepressant drugs has grown remarkably recently, and in clinical practice if unexpected side effects occur or therapeutic failure is observed during antidepressant drug treatment, the possible involvement of pharmacogenetic factors should be considered and the appropriate examinations be carried out. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

Año de publicación:

2008

Keywords:

• Human body
• metabolism
• Enzyme
• Clinical implications
• Examinations

Fuente:

scopus