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The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study

Published online by Cambridge University Press:  23 July 2013

Barbara Breitenstein ,
Sandra Scheuer ,
Hildegard Pfister ,
Manfred Uhr ,
Susanne Lucae ,
Florian Holsboer ,
Marcus Ising  and
Tanja M. Brückl
Barbara Breitenstein
Affiliation:
HolsboerMaschmeyer NeuroChemie, Munich, Germany Max Planck Institute of Psychiatry, Munich, Germany
Sandra Scheuer
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
Hildegard Pfister
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
Manfred Uhr
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
Susanne Lucae
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
Florian Holsboer
Affiliation:
HolsboerMaschmeyer NeuroChemie, Munich, Germany Max Planck Institute of Psychiatry, Munich, Germany
Marcus Ising
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
Tanja M. Brückl*
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
*
*Address for correspondence: Dr. Tanja Brückl, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804 München, Germany. (Email brueckl@mpipsykl.mpg.de)
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Abstract

Background

The gene product of the ABCB1 gene, the P-glycoprotein, functions as a custodian molecule in the blood–brain barrier and regulates the access of most antidepressants into the brain. Previous studies showed that ABCB1 polymorphisms predicted the response to antidepressants that are substrates of the P-gp, while the response to nonsubstrates was not influenced by ABCB1 polymorphisms. The aim of the present study was to evaluate the clinical application of ABCB1 genotyping in antidepressant pharmacotherapy.

Methods

Data came from 58 depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project, whose ABCB1 gene test results were implemented into the clinical decision making process. Hamilton Depression Rating Scale (HAM-D) scores, remission rates, and duration of hospital stay were documented with dose and kind of antidepressant treatment.

Results

Patients who received ABCB1 genotyping had higher remission rates [χ2(1) = 6.596, p = 0.005, 1-sided] and lower Hamilton sores [t(111) = 2.091, p = 0.0195, 1-sided] at the time of discharge from hospital as compared to patients without ABCB1 testing. Among major allele homozygotes for ABCB1 single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015 (TT/GG genotype), an increase in dose was associated with a shorter duration of hospital stay [rho(28) = –0.441, p = 0.009, 1-sided], whereas other treatment strategies (eg, switching to a nonsubstrate) showed no significant associations with better treatment outcome.

Discussion

The implementation of ABCB1 genotyping as a diagnostic tool influenced clinical decisions and led to an improvement of treatment outcome. Patients carrying the TT/GG genotype seemed to benefit from an increase in P-gp substrate dose.

Conclusion

Results suggest that antidepressant treatment of depression can be optimized by the clinical application of ABCB1 genotyping.

Keywords

ABCB1antidepressant treatment outcomemajor depressionP-glycoproteinpharmacogenetic testing

Information

Type
Original Research
Information
CNS Spectrums , Volume 19 , Issue 2 , April 2014 , pp. 165 - 175
Copyright
Copyright © Cambridge University Press 2013 

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Footnotes

Regardless of the order of the authors’ listed names, B. Breitenstein and S. Scheuer are joint first authors.

We thank Gertrud Ernst-Jansen, Karin Hofer, Elisabeth Kappelmann, Beate Siegel, Melanie Huber, Maik Ködel, and Susann Sauer for excellent technical assistance. Parts of the study were supported by a grant of the German Federal Ministry of Education and Research (BMBF), project no. 01KG0709.

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