German researchers have identified genetic variations that predict patient's response to two common antidepressants. Scientist at the Max Planck Institute of Psychiatry in Munich found 11 variants in the gene for a protective transporter protein called P-gp.
P-gb which removes drugs and other substances from the brain appears to negatively impact the effectiveness of certain antidepressants. Specifically the study found that citalopram (Celexa) and venlafaxine (Effexor).
In the initial part of the study the scientists rendered the genes ineffective for p-gb in mice and gave them the antidepressant. It was found that the concentrations if citalopram and venlafaxine in the brain were controlled by p-gb and that indicated that the antidepressants were substrates of the transporter protein.
The following step was verifying the genetics variants in 443 patients and determining whether the efficiency of the antidepressants was reduced.
"To our knowledge, our results provide for the first time evidence that genetic variants in the (gene for P-gp) account for differences in the clinical efficacy of antidepressants, most likely by influencing their access to the brain. The general conclusion to be drawn is that any drug treatment administered to treat CNS (central nervous system) diseases should be analyzed for its P-gp substrate status, which can be determined by using knockout mice. From a clinical point of view, the findings warrant that patients receiving a drug that is a P-gp substrate for the treatment of brain diseases are genotyped to exclude the possibility that a patient receives a drug that fails to enter the CNS to an extent required for efficacy," the researchers stated.
The researchers believe that any further development of antidepressants should establish if the drug is transported by P-gb and that drug trials should factor in the Pgb status of the participants.
[Source: YahooNews]
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