ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

• Published in: Human psychopharmacology Vol. 33; no. 1
• Main Authors: Papazisis, Georgios, Goulas, Antonios, Sarrigiannidis, Alexios, Bargiota, Stavroula, Antoniadis, Diomidis, Raikos, Nikolaos, Basgiouraki, Emmanouela, Bozikas, Vasileios P., Garyfallos, Georgios
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2018
• Subjects: ABCB1; Adult; Antipsychotic Agents - therapeutic use; Antipsychotics; ATP Binding Cassette Transporter, Subfamily B - genetics; Chlorpromazine; CYP2D6; CYP2D6 protein; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P450; Female; Gene polymorphism; Genotypes; Genotyping; Humans; Male; Mental disorders; naturalistic setting; Patients; Pharmacogenomic Variants; Polymerase chain reaction; Polymorphism, Single Nucleotide; polymorphisms; Psychosis; Psychotic Disorders - drug therapy; Psychotic Disorders - genetics; Restriction fragment length polymorphism; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - genetics; Statistical analysis; Treatment Outcome; treatment response; antipsychotics; ABCB1; CYP2D6; naturalistic setting; polymorphisms; treatment response
• ISSN: 0885-6222; 1099-1077
• DOI: 10.1002/hup.2644

Objectives The aim of our study was to examine the association between ABCB1 polymorphisms G2677T/A (rs2032582) and C3435T (rs1045642) and common CYP2D6 variants, with the response to antipsychotic treatment of psychotic patients, in a naturalistic setting, in Greece. Methods One hundred patients suffering from schizophrenia and other psychotic disorders were included in the study. Dosages were normalized to chlorpromazine equivalents. Response following 1 month of treatment was assessed as either a continuous variable, using the distribution of the corrected Positive and Negative Syndrome Scale percent change, or as a dichotomous variable defined as the number of patients scoring ≥30% from the corrected baseline Positive and Negative Syndrome Scale score. Genotyping was achieved with established polymerase chain reaction–restriction fragment length polymorphism methods. Results With response treated as a continuous variable, the homozygous recessive rs2032582 genotypes (TT) who were simultaneously carriers of a loss‐of‐function CYP2D6 allele (*4 or *5) responded significantly worse than the rest of the patients. Comparison of genotype frequencies revealed a statistically significant association of the above combination. No significant association between chlorpromazine equivalents and the tested genotypes was detected. Conclusion We have detected a possible interaction between ABCB1 and CYP2D6 in affecting response of psychotic patients to drug treatment, in a naturalistic setting.