Investigators at the Max Planck Institute of Psychiatry report that certain variants in the gene for a protective transporter protein P-gp compromise the effectiveness of certain antidepressants.
One reason for the poor response rates of antidepressants is that protective transporter proteins pump substances such as drugs and some hormones back into the bloodstream, which prevents them from crossing the blood-brain barrier, report the researchers.
The Max Plank scientists knocked out genes for the transporter protein in mice and administered the antidepressants 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 antidepressants, 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 antidepressants, most likely by influencing their access to the brain,” they wrote in their study, which will be published in the January 24 issue of Neuron.