Genetic difference predicts antidepressan...( Researchers have identified subtle g...),Health

Researchers have identified subtle genetic variations that predict the efficacy of two widely used antidepressant drugs. They found that certain variants in the gene for a protective transporter protein that pumps drugs and other substances out of the brain compromise the effectiveness of the antidepressants citalopram (trade name Celexa) and venlafaxine (Effexor).

The researchers said their findings indicate that genetic testing could help predict the responses of patients to particular antidepressants. More broadly, they said, such tests could help predict the efficacy of any drugs used to treat neurological disease.

Manfred Uhr and colleagues published their findings in the January 24, 2008, issue of the journal Neuron, published by Cell Press.

Antidepressants are the first-line treatment for major depression, but their overall clinical efficacy is unsatisfactory, as remission occurs in only one-third of the patients after a trial with an adequately dosed single drug, and remission rates further decline following successive treatment failures, wrote the researchers. This situation is particularly alarming in view of the fact that major depression constitutes one of the greatest disease burdens worldwide and is anticipated to be the second leading global disease burden by the year 2020, trailing only cardiovascular disease.

One reason for such poor response rates, said the researchers, is that protective transporter proteins pump such substances as drugs and some hormones back into the bloodstream, preventing them from crossing the blood-brain barrier.

In their studies, the researchers explored the function of one such transporter protein, called P-gp, in preventing the entry of antidepressants into the brain. They first knocked out genes for the transporter protein in mice and administered the antidepressants to the animals. The researchers found that brain concentrations of citalopram and venlafaxine were regulated
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