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.