Archive for the ‘ABCB1’ Category

An assortment of drugs, including 150mg Effexo...Image via Wikipedia Recent meta-analytical research, “Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy” (N Engl J Med 2008;358:252-60) reveals that while 94% of published antidepressant drug trials show positive findings, only 51% of all such (published and unpublished) trials show positive effects (with a range of effect sizes from 11-69%). This is probably not surprising to patients and physicians (investors? … well, maybe) who often search in vain, using trail and error, for a medication that can provide relief from major depression, one the the top disease burdens world-wide. Many have suggested that pharmacogenetics may provide a key to understanding the tremendous variability in medication response. For example, variations in the ABCB1, ATP-binding cassette sub-family B member 1, gene seem to predict who may show a response to certain antidepressants (citalopram, paroxetine, amitriptyline, and venlafaxine) medications, that are shuttled across the blood-brain-barrier endothelial membrane by ABCB1. In a pharmacogenetic medication trial involving 443 inpatients with depression who were treated at the Max Planck Institute of Psychiatry, the SNPs 2032583, rs2235015, rs2032583 and rs2235015 predict significantly different time course of response to treatment over 6 weeks. The paper, “Polymorphisms in the Drug Transporter Gene ABCB1 Predict Antidepressant Treatment Response in Depression” (doi: 10.1016/j.neuron.2007.11.017) is an example of pure and applied science at is best. The results pose a vexing dilemma for “really big” pharma however since the market size of genetic responders is obviously much smaller than market at large. Nevertheless, it seems inexorable change is underway.

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