1. Faculty of Medicine, Aristotle University of Thessaloniki, Greece
Association of common ABCB1 polymorphisms with response to antipsychotic therapy in a naturalistic setting: preliminary results
G. Papazisis1, A. Goulas3, A. Sarrigiannidis2, S.Ι. Bargiota2, D. Antoniadis2, D. Mpalaris2, A. Panderi3, V.P. Bozikas4, G. Garyfallos2
1 Department of Pharmacology and Clinical Pharmacology, 2 2nd Department of Psychiatry, st Department of Pharmacology, 4 1st Department of Psychiatry,
Faculty of Medicine, Aristotle University of Thessaloniki, Greece
INTRODUCTION
Individual response rates to antipsychotic drugs are subject to wide variation which may be due to genetic factors, among others. P-glycoprotein (P-gp) is an important efflux pump which could affect the intracerebral concentration of many antipsychotic drugs, by virtue of its localization on the blood-brain barrier [1]. Common polymorphisms of the P-gp – coding gene (ABCB1) have been associated in the past with response to antipsychotic therapy [2, 3]. The degree of association may be influenced by ethnicity however, warranting the gathering of relevant data concerning Greek patients for which no such study has been performed in the past. Here we report preliminary results from a study of the association of the rs (2677G>T/A) and rs (3435C>T) ABCB1 gene polymorphisms with response to combination therapy of Greek schizophrenic patients.
RESULTS
The mean age of the sample was 42 years old and the mean duration of illness was years. 70% of the patients were considered as responders and 30 % were non-responders. The mean chlorpromazine equivalent per day was mg for the responders and mg/day for the non-responders. So far, no statistically significant differences have been detected between initial responders and non-responders, with respect the genotype distribution of either polymorphism. Patients homozygous for the G allele of rs appear to receive higher - on average - doses of chlorpromazine equivalents, but that tendency is still non-significant. No significant association was observed between chlorpromazine equivalents administered and ABCB1 genotype, sex, age or time from initial diagnosis.
MATERIALS AND METHODS
The study is undertaken in its natural setting and involves the administration of both first and second generation antipsychotic drugs to consecutive patients of the 2nd Department of Psychiatry of our Medical Faculty. 56 schizophrenic patients including seventeen females were enrolled. Written informed consent was obtained after explanation of the purpose and design of the study. Patients with a history of alcohol or drug abuse were excluded from the study as well as patients under co-medication with drugs affecting the activity and/or expression of P-gp. Antipsychotic dosages were converted to common chlorpromazine equivalents for purposes of comparison. Response following one month of treatment was assessed with the PANSS scale for efficacy and the Simpson-Angus scale for extrapyramidal adverse effects. Response was defined as a ≥30% change in the total PANSS score. ABCB1 genotyping was performed with established RFLP protocols and custom genotyping assays using a real-time PCR setup. The χ2 test of independence and ANCOVA tests were used for statistical analysis.
DISCUSSION
The ABCB1 2677G>T/A and 3435C>T polymorphisms do not appear to affect the initial response to antipsychotic drugs significantly, in our setting. Patients homozygous for the G allele of rs could be more refractory to antipsychotic drug treatment but the results need to be validated further in a larger sample size.
DISCLOSURE: This poster does not have a conflict of interest
REFERENCES
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