Clinical implications of pharmacogenetics of antidepressants

Several antidepressants, i.e., desipramine, fluvoxamine, maprotiline, mianserin, nortriptyline and paroxetine, are metabolised predominantly by the polymorphic cytochrome P450 (CYP) 2D6. This metabolic characteristic leads to CYP2D6-mediated drug interactions. Except fluvoxamine and maprotiline, significant relationships have been reported between the steady-state plasma concentrations (Css) of these drugs and the CYP2D6 polymorphism. There have been very few studies on the relationship between therapeutic effects of antidepressants and the CYP2D6 polymorphism, and to date a significant relationship has been reported for mianserin, but not for desipramine. Meanwhile, severe side effects of desipramine and nortriptyline have been associated with deficient CYP2D6 activity. The CYP2D6 phenotyping and genotyping appear to be useful for the prediction of the Css and prevention of side effects of some antidepressants. However, further systematic studies are necessary to prove the usefulness of these techniques for the optimization of antidepressant effects. (C) 2002 Elsevier Science B.V All rights reserved.