¹Center for Pharmacogenomics and Clinical Pharmacology, UCLA, University of Beira Interior, University of Extremadura, Los Angeles, CA

^*Supported by NIH grants GM61394, RR017365, RR000865, RR16996 and by an award from the Dana Foundation, and by grants from Spanish Ministry of Education and Science from the Spanish Ministry of Education and Science (SAF2004.05716 and PR2004.0576).

Abstract

Background/Aims: We have found the implication of CYP2C9 in the metabolism of fluoxetine in patients. The aim of the present study was to analyze the role of CYP2C9 in the clinical response to antidepressant drugs in Mexican-American Depressive Patients (MADP).

Methods: CYP2C9 genotypes were studied in 220 MADP (at least three out of four grandparents born in Mexico) treated in an eight-week double-blind study either with fluoxetine or desipramine. They were divided in Completers (n=138) those whom terminated the study and Dropouts (n=47), those that could not finalize the study due to side effects or other medical condition. A group of 25 did not initiate the study and 10 were Placebo responders.

Results: The percentage of CYP2C9*3 was higher in Dropouts compared to Completers (6.4 vs. 2.9%; OR=2.28). In the group treated with fluoxetine this percentage was much higher among Dropouts compared to Completers (11.7 vs. 3.4%; OR=3.76). However, in the group treated with desipramine the percentages were very similar (3.3% vs. 2.3%). Interestingly all Placebo responders were CYP2C9*1/*1 (wild type).

Conclusions: The present preliminary results seem to support a role for CYP2C9*3 in the clinical outcome of MADP treated with fluoxetine, whereas during desipramine treatment seems to be less relevant.