title: CYP2D6 poor metabolizer status might be associated with better response to risperidone treatment.
abstract: The variability in the antipsychotic response is, to some extent, genetically determined. Several studies have attempted to establish a role for genetic variation in genes coding pharmacokinetic and pharmacodynamic targets, but to date, no definite genetic predictive marker has been identified. We aimed to explore the putative role of 19 genetic variants and risperidone clinical improvement in 76 White schizophrenic inpatients, measured as change in Positive and Negative Syndrome Scale (PANSS). CYP2D6 poor metabolism was significantly associated with greater clinical improvement in total PANSS and a trend was also found for MDR1 3435C>T to higher total PANSS scores in 3435T carriers. This study suggests the importance that genetic variability on pharmacokinetic factors may have in risperidone response and gives evidence for the need for further investigation in order to establish the actual predictive value and clinical utility that CYP2D6 genotyping might have in risperidone therapy management.
authors.affiliation: Departments of aGenetics and Genomics bPsychiatry, IIS - Fundacion Jimenez Diaz University Hospital cCIBERER ISCIII dDepartment of Biology, Autonomous University of Madrid, CBMSO, CSIC eDepartment of Clinical Pharmacology, La Princesa University Hospital, IIS Princesa fCIBEREHD ISCIII gDepartment of Preventive Medicine, Public Health and Medical Immunology and Microbiology, School of Health Sciences, Rey Juan Carlos University hCIBERSAM ISCIII, Madrid iCICAB, Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain jDepartment of Psychiatry, Columbia University, New York, New York, USA.
authors.forename: Berta
authors.initials: B
authors.lastname: Almoguera
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Jorge
authors.initials: J
authors.lastname: Lopez-Castroman
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Concepción
authors.initials: C
authors.lastname: Vaquero-Lorenzo
authors.forename: José
authors.initials: J
authors.lastname: Fernandez-Piqueras
authors.forename: Adrián
authors.initials: A
authors.lastname: Llerena
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
authors.forename: Enrique
authors.initials: E
authors.lastname: Baca-García
authors.forename: Rafael
authors.initials: R
authors.lastname: Dal-Ré
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone