Optimizing antidepressant treatment dosage based on ABCB1 gene variants – Results from a randomized clinical study

The gene product of the ABCB1 gene, the P-glycoprotein (P-gp), functions as a custodian molecule in the blood-brain barrier extruding its substrates and thereby limiting their passage to the brain. ABCB1 polymorphisms rs2032583 and rs2235015 predicted the response to antidepressants with P-gp substrate properties (Uhr et al., 2008). The aim of this study was to evaluate an ABCB1 genotype-dependent efficacy of a quick dose-escalation strategy. Depressed inpatients (n = 73) treated with antidepressant that are P-gp substrates were randomly assigned to a standard or high dose condition for 28 days. HAM-D scores, adverse effects and plasma levels were measured weekly and tested among two intronic ABCB1 SNPs rs2032583 and rs2235015. A treatment as usual (TAU) control sample (n = 128) was retrospectively matched by gender, age, diagnosis. There was an interaction of genotype x plasma group: Minor allele carriers of rs2032583 whose plasma levels were within the recommended range had a greater symptom reduction than the TAU group [for rs2032583:F(1,163) = 4.366,p = 0.038]. Minor allele carriers in the high plasma group had more sleep disturbances than those in the normal plasma group and noncarriers. The treatment of MDD can be optimized by ABCB1 genotyping combined with monitoring of plasma drug concentration: For minor allele carriers of rs2032583 and rs2235015, antidepressant plasma levels should not exceed the recommended range in order to obtain optimal treatment outcome. This study was supported by HMNC GmbH