Pharmacogenomics of Antipsychotic Drugs

Abstract

Pharmacogenomic research of antipsychotic drug (APD) response continued to produce interesting findings in the past few years. Several genetic markers have been shown to be reliably associated with APD responses including efficacy and drug-induced adverse reactions. For APD treatment response, DRD2 has been shown to predict symptom reduction and APD efficacy. For APD-induced weight gain, a recent meta-analysis supports the associations with HTR2C and MC4R variants, as well as several other genetic markers. For clozapine-induced agranulocytosis, an independent sample has confirmed the association with HLA-DQB1. In addition, a multi-marker combination approach has been studied to increase the predictive power for APD response. However, these markers’ sensitivity and specificity are not high enough to be used in routine clinical practice. They may have some value in certain situations such as treatment refractory cases, and they need to be used in conjunction with other clinical predictors. Due to the polygenetic nature of drug response, the new polygenetic risk score method appears promising in combining many genetic markers in predicting clinical response. The current review focused on pharmacodynamic genes (i.e., drug target), and did not touch upon pharmacokinetic genes such as cytochrome P450 genes (e.g., CYP2D6), which have been shown to influence APD response especially adverse reactions. Future research should use a multi-marker approach to combine both pharmacodynamic and pharmacokinetic genes, as well as known clinical factors, to increase the predictive power for APD clinical response.