Failure to Replicate Genetic Associations with Antidepressant Treatment Response in Duloxetine-Treated Patients

Abstract

Recent studies have identified associations of polymorphisms in several target genes with antidepressant treatment response of serotonin reuptake inhibitors and a tricyclic antidepressant. We sought to replicate these associations in a study of a serotonin-norepinephrine reuptake inhibitor. In 250 outpatients with nonpsychotic major depressive disorder, response to treatment with once-daily duloxetine (60 mg/day) over 6 weeks was examined for associations with polymorphisms in eight candidate genes previously associated with antidepressant response using mixed-effect model repeated-measures analysis. Treatment response was quantified on the basis of changes from baseline using 17-item Hamilton Depression Rating Scale total scores. Polymorphisms in PDE1A, PDE1C, PDE6A, PDE11A, ABCB1, GRIK4, SLC6A4, and OPRM1 genes showed no statistically significant associations (uncorrected, two-tailed p > .05) with duloxetine treatment response. Previously, described associations between polymorphisms in candidate genes and antidepressant treatment response were not replicated in this study. This result may suggest that previous associations are specific to serotonin reuptake inhibitors.