ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression

Singh, A. B., Bousman, C. A., Ng, C. H., Byron, K. and Berk, M. 2012, ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression, Translational psychiatry, vol. 2, no. Article no. 198, pp. 1-6.

Attached Files
Name Description MIMEType Size Downloads

Title ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression
Author(s) Singh, A. B.
Bousman, C. A.
Ng, C. H.
Byron, K.
Berk, M.
Journal name Translational psychiatry
Volume number 2
Issue number Article no. 198
Start page 1
End page 6
Total pages 6
Publisher Nature Publishing Group
Place of publication London, England
Publication date 2012-11-27
ISSN 2158-3188
Keyword(s) ABCB1
pharmacogenetics
antidepressant
major depression
blood–brain barrier
P-glycoprotein
Summary The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood–brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N=113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P=0.0001). This equates to a 2.0- (95% confidence interval=1.5–3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio=6.69; 95% confidence interval=1.72–25.9, P=0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD.
Language eng
Field of Research 110399 Clinical Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, Macmillan Publishers Limited
Persistent URL http://hdl.handle.net/10536/DRO/DU:30050605

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in TR Web of Science
Scopus Citation Count Cited 12 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 95 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Mon, 18 Feb 2013, 09:20:16 EST by Jane Moschetti

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.