11 Feb 2008

Genes key to antidepros?

German researchers have discovered that genetic factors play a role in the effectiveness of anti-depressant medications, explaining why some individuals take well to anti-depressants and others complain of bad side-effects.

The researchers at the Max Planck Institute of Psychiatry said their findings indicate that genetic testing could help predict the responses of patients to particular anti-depressants.

More broadly, they said, such tests could help predict the effectiveness of any drugs used to treat neurological disease.

Dr Manfred Uhr and colleagues published their findings in the January 24 issue of the journal Neuron.

Treatment not that effective
"Anti-depressants 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.

How the study was conducted
The Max Plank scientists knocked out genes for the transporter protein in mice and administered the anti-depressants to the animals.

They found that P-gp regulated brain concentrations of Forest laboratories' Celexa and Wyeth Pharmaceuticals' Effexor. The researchers explain that the antidepressants were thus substrates of the transporter.

Studying 443 patients on the anti-depressants, they next searched for variants in the human gene that correlated with reduced efficacy of the drugs. Their genetic analysis identified 11 such variants.

"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 anti-depressants, most likely by influencing their access to the brain," they wrote. – (Sapa-dpa)