Failure to replicate genetic associations with antidepressant treatment response in duloxetine-treated patients.

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

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