Therapy response prediction in major depressive disorder: current and novel genomic markers influencing pharmacokinetics and pharmacodynamics.

Abstract

Major depressive disorderis connected withhigh rates of functional disability and mortality. About athird of the patients are at risk of therapy failure. Several pharmacogenetic markersespecially located in CYP450 genes such as CYP2D6 or CYP2C19 are of relevance for therapy outcome prediction in major depressive disorder but a further optimization of predictive tools is warranted. The article summarizes the current knowledge on pharmacogenetic variants, therapy effects and side effects of important antidepressive therapeutics, and sheds light on new methodological approaches for therapy response estimation based on genetic markers with relevance for pharmacokinetics, pharmacodynamics and disease pathology identified in genome-wide association studyanalyses, highlighting polygenic risk score analysis as a tool for further optimization of individualized therapy outcome prediction.