The Clinical Impact of ABCB1 Polymorphisms on the Treatment of Psychiatric Diseases

Marcus      C. Rosenhagen; Manfred      Uhr

Abstract

Polymorphisms in the drug transporter gene ABCB1 account for differences in the clinically efficacy of the most drugs, most likely by influencing their access to the brain. The majority proportion of depressed patients, given a regular dose, do not respond properly or experience severe side effects. One explanation may be the polymorphisms in the drug transporter gene ABCB1, which account for differences in the clinical efficacy of antidepressants, neuroleptics or mood stabilizers most likely by influencing their access to the brain. If patients are treated with a substrate of P-gp, functionally relevant genetic variants in the ABCB1 transporter could influence intracerebral drug concentrations and, thereby, clinical response. The review shows recently investigated clinical impact of ABCB1 variants including the three most important SNPs rs1045642, rs2032582, and rs2032583. In the paper, with respect not to go beyond the scope of this review, we will focus on these three SNPs. The final goal of pharmacogenetics is to help clinicians to choose the best treatment for each individual patient. From the evidence reviewed in this publication, it is likely that combination of metabolizing and drug target polymorphisms will produce the best prediction for the selection of the optimal dose and optimal drug as a function of the individual s genetic profile.

Keywords: ABCB1 transporter, P-glycoprotein, single nucleotide polymorphism, pharmacogenetic, amitriptyline, nortriptyline, antipsychotics, sulpiride, antidepressants, antiepileptics