Fluoxetine pharmacogenetics in child and adult populations

Abstract

Although fluoxetine is useful in the treatment of major depression, 30-40 % of the patients do not respond to therapy. The response seems to be influenced by certain genes which are involved in the drug's pharmacodynamics and pharmacokinetics. The present study reviews the literature on genetic contributions to fluoxetine response in children and adults, and concludes that the different polymorphisms of CYP2D6 and CYP2C9 may influence the blood concentrations of fluoxetine. If the childhood dose is adjusted for weight, differences between children and adults are unlikely. As regards the genes that influence the drug's pharmacodynamics, polymorphisms of SLC6A4, HTR1A and MAO-A seem to be involved in the response to fluoxetine, while the genes COMT, CRHR1, PDEA1, PDEA11 GSK3B and serpin-1 also seem to play a role. Comparison of different studies reveals that the results are not always consistent, probably due to methodological differences. Other factors such as gender or ethnicity may also influence treatment response.