Personalized Medicine: Pharmacogenetics in Psychiatry

Jan   van der   Weide; John   W.J.   Hinrichs

Abstract

Pharmacogenetics has made its entrance in psychiatry since the discovery of the first polymorphism directly correlated to individual variability in Cytochrome P450 (CYP) metabolism. Currently, most of the major drugmetabolizing CYP enzymes, their specific CYP-drug relationships and many of their gene variants are known. This has led to the development of elegant models predicting individualized dose recommendations. This has however not yet resulted in a widespread implementation of CYP genotyping in daily practice, mainly due to unfamiliarity and lack of prospective data. Recently it has been shown that therapeutic drug monitoring with additional CYP genotyping improved the treatment with antidepressants of patients in the general practice setting. Considerable effort has been put into developing a FDA approved DNA microarray, identifying multiple clinical relevant CYP polymorphisms at once. This could pave the way for a wide implementation of pharmacogenetic testing in the clinical environment. Individual variability in drug response is not explained by variation of drug metabolism alone. Polymorphisms in neurotransmitter-receptor genes are gaining more interest since they are at the end of the line in determining psychotropic drug effects. Several studies have already shown that the response of antipsychotic drugs and antidepressants can be predicted by genotyping polymorphisms in serotonin receptors and transporter genes. The increased predictability of the different determinants in drug efficacy brings us a step closer to personalized medicine in psychiatry.

Keywords: Antidepressant, antipsychotic, cytochrome P450, polymorphism, dose adjustment, serotonin, dopamine