P.2.a.004 The clinical utility of ABCB1 genotyping in antidepressant treatment

Abstract

Objective: The gene product of the ABCB1 gene, the P-glycoprotein (P-gp), functions as a custodian molecule in the blood brain barrier and regulates the access of most antidepressants into the brain. Studies showed that ABCB1 polymorphisms predict the response to antidepressants that are substrates of the P-gp, whereas the response to non-substrates was not influenced by ABCB1 polymorphisms (Uhr et al., 2008). The aim of the present study was to evaluate the clinical utility of ABCB1 genotyping in clinical depression therapy. Methods: Data came from 57 depressed inpatients from the MARS (Munich-Antidepressant-Response-Signature, www.marsdepression. de) study whose ABCB1 gene test results were implemented into the clinical decision making process. Hamilton scores, remission rates and duration of hospital stay were documented with dosage and kind of antidepressant treatment. Results: The group where ABCB1 genotyping was conducted had higher remission rates (Chi-square(1)=3.436, p=0.032, one-sided test) and lower Hamilton sores (t(22.72)=x1.780, p=0.044, one-sided test) at the time of discharge from hospital as compared to a group without ABCB1 testing. Among patients with the less favourable genotype, an increase in dosage was associated with a shorter duration of hospital stay (rho(24)=x0.364, p=0.034, one-sided test) whereas other treatment strategies (e.g., switching to a non-substrate) showed no significant associations with treatment outcome. Conclusion: Results suggest that the treatment of depression can be optimized by an application of an ABCB1 gene test. Especially patients carrying the unfavourable ABCB1 genotype that impedes brain penetrance seem to benefit from an increase in dosage. The efficacy of specific ABCB1 genotype-dependent treatment strategies is currently tested in a controlled prospective clinical study.