Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression

Neuron. 2008 Jan 24;57(2):203-9. doi: 10.1016/j.neuron.2007.11.017.

Abstract

The clinical efficacy of a systemically administered drug acting on the central nervous system depends on its ability to pass the blood-brain barrier, which is regulated by transporter molecules such as ABCB1 (MDR1). Here we report that polymorphisms in the ABCB1 gene predict the response to antidepressant treatment in those depressed patients receiving drugs that have been identified as substrates of ABCB1 using abcb1ab double-knockout mice. Our results indicate that the combined consideration of both the medication's capacity to act as an ABCB1-transporter substrate and the patient's ABCB1 genotype are strong predictors for achieving a remission. This finding can be viewed as a further step into personalized antidepressant treatment.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Depression / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Statistics, Nonparametric

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antidepressive Agents
  • Abcb1b protein, mouse