Genetics May Determine Antidepressants' Effectiveness
WEDNESDAY Jan. 23, 2008 -- Genetic variations that predict patient response to the two common antidepressant drugs citalopram (brand name Celexa) and venlafaxine (Effexor) have been identified by German researchers.
The team at the Max Planck Institute of Psychiatry in Munich found that 11 variants in the gene for a protective transporter protein called P-gp, which removes drugs and other substances from the brain, compromise the effectiveness of these two drugs.
In the first part of the study, the researchers knocked out genes for P-gp in mice and gave them antidepressants. They found that brain concentrations of citalopram and venlafaxine were regulated by P-gp, indicating that the antidepressants were "substrates" of the transporter protein.
Next, the team analyzed 443 people on antidepressants for genetic variants that correlated with reduced efficacy of the two antidepressants.
"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 researchers wrote.
The findings, published in the Jan. 24 issue of the journal Neuron, suggest that genetic testing could help predict how individual patients would react to specific antidepressants, the researchers said.
They added that genetic tests may also help predict the effectiveness of any drugs used to treat neurological diseases.
"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 study authors wrote.
Future development of antidepressants should take into account whether new drugs are transported by P-gp, and clinical trials of antidepressant drugs need to factor in the P-gp genetic status of participants, the researchers recommended.
The U.S. National Institute of Mental Health has more about depression.
Posted: January 2008
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