TY - JOUR
T1 - Pharmacogenetics of antipsychotics
T2 - Clinical utility and implementation
AU - Arranz, Maria J.
AU - Salazar, Juliana
AU - Hernández, Marta H.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/3/5
Y1 - 2021/3/5
N2 - Decades of research have produced extensive evidence of the contribution of genetic factors to the efficacy and toxicity of antipsychotics. Numerous genetic variants in genes controlling drug availability or involved in antipsychotic processes have been linked to treatment variability. The complex mechanism of action and multitarget profile of most antipsychotic drugs hinder the identification of pharmacogenetic markers of clinical value. Nevertheless, the validity of associations between variants in CYP1A2, CYP2D6, CYP2C19, ABCB1, DRD2, DRD3, HTR2A, HTR2C, BDNF, COMT, MC4R genes and antipsychotic response has been confirmed in independent candidate gene studies. Genome wide pharmacogenomic studies have proven the role of the glutamatergic pathway in mediating antipsychotic activity and have reported novel associations with antipsychotic response. However, only a limited number of the findings, mainly functional variants of CYP metabolic enzymes, have been shown to be of clinical utility and translated into useful pharmacogenetic markers. Based on the currently available information, actionable pharmacogenetics should be reduced to antipsychotics’ dose adjustment according to the genetically predicted metabolic status (CYPs’ profile) of the patient. Growing evidence suggests that such interventions will reduce antipsychotics’ side-effects and increase treatment safety. Despite this evidence, the use of pharmacogenetics in psychiatric wards is minimal. Hopefully, further evidence on the clinical and economic benefits, the development of clinical protocols based on pharmacogenetic information, and improved and cheaper genetic testing will increase the implementation of pharmacogenetic guided prescription in clinical settings.
AB - Decades of research have produced extensive evidence of the contribution of genetic factors to the efficacy and toxicity of antipsychotics. Numerous genetic variants in genes controlling drug availability or involved in antipsychotic processes have been linked to treatment variability. The complex mechanism of action and multitarget profile of most antipsychotic drugs hinder the identification of pharmacogenetic markers of clinical value. Nevertheless, the validity of associations between variants in CYP1A2, CYP2D6, CYP2C19, ABCB1, DRD2, DRD3, HTR2A, HTR2C, BDNF, COMT, MC4R genes and antipsychotic response has been confirmed in independent candidate gene studies. Genome wide pharmacogenomic studies have proven the role of the glutamatergic pathway in mediating antipsychotic activity and have reported novel associations with antipsychotic response. However, only a limited number of the findings, mainly functional variants of CYP metabolic enzymes, have been shown to be of clinical utility and translated into useful pharmacogenetic markers. Based on the currently available information, actionable pharmacogenetics should be reduced to antipsychotics’ dose adjustment according to the genetically predicted metabolic status (CYPs’ profile) of the patient. Growing evidence suggests that such interventions will reduce antipsychotics’ side-effects and increase treatment safety. Despite this evidence, the use of pharmacogenetics in psychiatric wards is minimal. Hopefully, further evidence on the clinical and economic benefits, the development of clinical protocols based on pharmacogenetic information, and improved and cheaper genetic testing will increase the implementation of pharmacogenetic guided prescription in clinical settings.
KW - Antipsychotics
KW - CYPs
KW - Implementation
KW - Personalised medicine
KW - Pharmacogenetics
KW - Pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=85098142956&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000608605700002&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.bbr.2020.113058
DO - 10.1016/j.bbr.2020.113058
M3 - Article
C2 - 33316324
AN - SCOPUS:85098142956
SN - 0166-4328
VL - 401
JO - Behavioural Brain Research
JF - Behavioural Brain Research
M1 - 113058
ER -