Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy

Pharmacogenetics studies the genetic basis of an individual's ability to re spond to pharmacotherapy. Variability of this response is a major problem. Fatal adverse drug reactions have been reported to be the fourth leading ca use of death in the US. In depression. 30-40% of all patients do not respon d sufficiently to the initial treatment and it can take up to 6 weeks for t hem to be identified. Much knowledge has been gathered throughout the last 3 decades about the genetic basis of pharmacokinetic variability. Generic t ests suitable for the routine laboratory are now available for some importa nt metabolizing enzymes (e.g., CYP2D6, CYP2C19) identifying those individua ls who are slow or fast metabolizers of certain drugs, many of which are wi dely used in the treatment of depression (e.g., tricyclic antidepressants). The possible use of these tests in the clinical practice of monitoring ant idepressant therapy is discussed in relation to older phenotyping methods a nd therapeutic drug monitoring. Less well studied than the genetics of pharmacokinetics is the genetic basi s of pharmacodynamic variability. As: selective serotonin reuptake inhibito rs (SSRI) have a wide therapeutic index. pharmacokinetic variability usuall y does nor explain insufficient response to therapy. Recently. some excitem ent was caused by reports on serotonin transporter gene polymorphisms and t heir influence on the response to antidepressive therapy with SSRIs as this could provide an interesting diagnostic tool in assessing the chances of r esponse to the: most popular group of antidepressants at present. Current k nowledge in this young field of research is summarized. (C) 2001 Elsevier S cience B.V. All rights reserved.