MDR1 gene polymorphisms and response to acute risperidone treatment

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2010-03, Vol.34 (2), p.387-392
• Main Authors: Kastelic, Matej, Koprivšek, Jure, Plesničar, Blanka Kores, Serretti, Alessandro, Mandelli, Laura, Locatelli, Igor, Grabnar, Iztok, Dolžan, Vita
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Adverse effects; Analysis of Variance; Antipsychotic Agents - blood; Antipsychotic Agents - therapeutic use; Antipsychotics; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Female; Genetic Association Studies; Genotype; Humans; Male; Medical sciences; Middle Aged; Movement Disorders - etiology; Neuropharmacology; Pharmacogenetics; Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychotic Disorders - drug therapy; Psychotic Disorders - genetics; Risperidone - blood; Risperidone - therapeutic use; Schizophrenia; Schizophrenia - blood; Schizophrenia - complications; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenic Psychology; Slovenia; Statistics, Nonparametric; Toxicity: nervous system and muscle; Treatment response; Young Adult
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2010.01.005

Polymorphic multidrug resistant protein 1 (MDR1) transports drugs against a concentration gradient across the blood–brain barrier and reduces their accumulation in the brain. MDR1 may therefore influence antipsychotic brain availability contributing to inter-individual differences in treatment response and adverse effects, regardless of plasma concentrations. In the present study we investigated the influence of two common MDR1 polymorphisms on the improvement of psychopathological symptoms and occurrence of extrapyramidal side effects (EPS) in Slovenian schizophrenia patients acutely treated with risperidone. A total of 59 clinically well defined patients with first episode schizophrenia spectrum disorders or after tapering their maintenance treatment were genotyped for MDR1 C3435T and G2677T/A. Steady-state plasma concentrations of risperidone active moiety (sum of risperidone and the 9-hydroxyrisperidone) were determined. G2677T/A and C3435T genotypes were not associated to psychopathological symptoms, efficacy of treatment and risk for parkinsonism. Marginal associations with akathisia ( p = 0.039 and p = 0.042, respectively) and dystonia ( p = 0.013 and p = 0.034, respectively) were observed for both G2677T/A and C3435T genotypes. However, higher AIMS and BARS scores were observed only in heterozygous carriers of G2677T/A and C3435T polymorphisms and there was no tendency of gene–dose effect. The present study does not suggest a major influence of MDR1 G2677T/A and C3435T polymorphisms on treatment response during short-term risperidone therapy in patients with schizophrenia or schizoaffective disorder.