The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study. (23rd July 2013)

• Record Type: Journal Article
• Authors: Breitenstein, Barbara; Scheuer, Sandra; Pfister, Hildegard; Uhr, Manfred; Lucae, Susanne; Holsboer, Florian; Ising, Marcus; Brückl, Tanja M.
• Is Part Of: CNS spectrums. Volume 19:Number 2(2014:Apr.)
• Page Start: 165
• Page End: 175
• Publication Date: 2013-07-23
• Subjects: Neuropsychiatry -- Periodicals; Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1017/S1092852913000436
• Languages: English
• ISSNs: 1092-8529

Abstract

<abstract abstract-type="normal"> <title> <x content-type="archive" xml:space="preserve">Abstract</x> </title> <sec id="abs1" sec-type="general"> <title>Background</title> <p>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.</p> </sec> <sec id="abs2" sec-type="methods"> <title>Methods</title> <p>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.</p> </sec> <sec id="abs3" sec-type="results"> <title>Results</title> <p>Patients who received ABCB1 genotyping had higher remission rates [χ<sup>2</sup>(1) = 6.596, <italic>p</italic> = 0.005, 1-sided] and lower Hamilton sores [<italic>t</italic>(111) = 2.091, <italic>p</italic> = 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 [<italic>rho</italic>(28) = –0.441, <italic>p</italic> = 0.009, 1-sided], whereas other treatment strategies (eg, switching to a nonsubstrate) showed no significant associations with better treatment outcome.</p> </sec> <sec id="abs4" sec-type="discussion"> <title>Discussion</title> <p>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.</p> </sec> <sec id="abs5" sec-type="conclusion"> <title>Conclusion</title> <p>Results suggest that antidepressant treatment of depression can be optimized by the clinical application of ABCB1 genotyping.</p> </sec> </abstract>