Objective: Pharmacogenetic studies have identified genetic variants associated with fluoxetine response in patients with major depression disorder (MDD). The serotonin transporter gene is the principal site of action of selective serotonin reuptake inhibitors. Previous studies analyzing SLC6A4 gene variants are inconsistent and differ among populations. The aim of the present study was to analyze the association between 5-HTTLPR/rs24531 triallelic polymorphism and fluoxetine response in Mexican patients with MDD.
Methods: We analyzed a sample of 150 patients with MDD. Fluoxetine response was assessed according to a reduction in the Hamilton Depression Rating Scale and Montgomery Depression Rating Scale scores of 50% or more at 8 weeks from baseline. In addition, we analyzed the genotype and allele distribution between responder and nonresponder patients in a subgroup of very severe depression patients.
Results: We did not find association between fluoxetine responders and 5-HTTLPR/rs25531 variants (P = 0.0637). However, in the analysis of severe depression at baseline (Hamilton Depression Rating Scale ≥ 25), we observed a high frequency of low activity alleles (S/LG) in nonresponders patients (P = 0.0102).
Conclusions: Our findings showed an association between low activity alleles of SLC6A4 gene and fluoxetine nonresponse in patients with severe depression.