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Posts Tagged ‘Antidepressant’

Relief of big pharma’s antidepressant blues is as easy as ABC ?

Posted in ABCB1, tagged , , , on February 14, 2008| Leave a Comment »

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that while 94% of published antidepressant drug trials show positive findings, only 51% of all such (published and unpublished) trials show positive effects (with a range of effect sizes from 11-69%).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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Sweatin’ to the oldies, VGF-style

Posted in Hippocampus, VGF, tagged , , , on December 18, 2007| Leave a Comment »

Richard Simmons. Cropped from a photo by Del F...Image via Wikipedia The Wall Street Journal just ran a piece on the growing use of electro-convulsive (“shock”) therapy in elderly patients suffering from severe depression. While the clinical evidence may show this approach is effective – albeit scary – it is notable that another study published on the same day by Hunsberger et al., entitled, “Antidepressant actions of the exercise-regulated gene VGF ” (DOI). This paper reveals that a number of genes possessing antidepressant-like properties are induced by exercise. Yes, good old fashioned walkin’ and sweatin’. A few clinical trials have shown that, in older people especially, exercise is just as effective as anti-depressant medications. Furthermore, exercise seems to increase neurogenesis in the hippocampus in a manner that is parallel to anti-depressants. One of the genes induced by exercise, a growth factor named VGF, produces anti-depressant responses when administered into the mouse brain, while +/- hemizygous VGF animals show increased physiological and behavioral signs of stress. The authors point to the role of structural synaptic changes in long-term relief of depression, rather than short term increases in serotonin, but -ironically – note that VGF would be a great candidate for drug development. Hmmm, seems like I’ll skip the meds and the electrodes, and get to sweatin’ with a Richard Simmons video.*

*For the record, I do not currently own a Richard Simmons video.

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AMPA receptor polymorphisms add to antidepressant – suicide puzzle

Posted in 5HTT, AMPA receptor, Glutamate, GRIA3, GRIK2, tagged , , , , on September 1, 2007| Leave a Comment »

Oil on canvasImage via Wikipedia The recent paper, “Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression” finds that among 68 candidate genes, markers for 2 AMPA-type glutamate receptors (rs4825476, rs2518224: GRIA3 and GRIK2) show significant association in 120 individuals who experienced suicidal ideation in a large medication trial for major depressive disorder. Many families with loved ones suffering from depression remain wary and confused about a possible causal relationship between selective serotonin reuptake inhibitor (SSRI) antidepressants and suicide. A current FDA-mandated black box warning advises youths on the potential risks. This recent genetic study seems to provide a meaningful step forward in better understanding the mechanism of shifts in mood and cognition that occur in some individuals. But like many brain research studies though, shining a tiny ray of light on a puzzle suddenly illuminates massive complexities, previously unseen. A great deal of research shows that SSRI exposure leads to long lasting changes in AMPA receptor expression, localization and function, – but it’s unclear where a specific link between this and changes in mood and cognition will be drawn.

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