Genes May Determine Antidepressant Success Rates
> 1/30/2008 8:39:21 AM

A common mutation in a gene responsible for repelling foreign substances from the central nervous system may be to blame for the failure of antidepressant medications in a large portion of the affected population.

A near-majority of patients who suffer from depression and receive relevant prescriptions fail to reap the full benefits of traditional medications; many do not witness any sort of improvement, and a great many more report only minor incremental shifts in mood even after taking said medicines for several weeks or months. Any single antidepressant facilitates full recovery in only 1/3 of affected patients. Previous genetic tests designed to predict antidepressant success rates have proven less than reliable, but new research seems more promising; neurologists have identified the particular genotype responsible for a large share of the treatment-resistant depression that is, unfortunately, the most common variety.

The ABCB-1 (or multidrug resistance 1) gene activates a certain chemical transportation mechanism responsible for moving given substances across the "blood brain barrier" and into the central nervous system (CNS); it also acts to push them back out of the CNS and around the circulatory system, moderating their presence in the brain and the body at large. If the gene reacts adversely to a certan chemical, it will bar that substance from entering the brain - a very effective defense mechanism designed to keep potentially damaging chemicals out. But unidentified drugs meant to counteract depression symptoms may, erroneously, be identified as antagonists in those individuals bearing a particular malformation of the ABCB-1 gene. By hindering the drug's ability to enter the CNS and alter the functions therein, this polymorphic gene prevents certain affected SSRIs from doing their job.

In order to determine which medications were ABCB-1 substrates (substances against which the enzyme responds negatively), German researchers administered the medications to a group of control rats as well as a group bred to lack the rodent equivalent of the human ABCB-1 gene. The problem drugs, including the popular Celexa and Effexor SSRIs, were identified by greater representative quantities in the brains of the genetically polymorphic rats than in those whose nervous systems developed without human interference; the genetic abnormalities present in the test rats prevented these meds from being distributed evenly throughout the brain and the body. After completing these tests, researchers performed the same on a group of 443 human patients, separating them into groups based on whether their antidepressants had been classified as ABCB-1 substrates. They found more than ten specific variations on this one gene, two of which were deemed particularly influential in the regulation of brain chemicals and proteins relating to AD meds.

The most significant implications of this study, of course, involve a greater ability to determine which medications will prove most effective for individual patients. Expanding our general knowledge of the related processes will also allow for the future development of more effective medications specifically tailored for individuals with these abnormalities. Patients who are frustrated by a lack of results from their prescribed meds should not grow too anxious; their genetic makeup might simply mean that other meds will ultimately prove more effective.

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