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.
Perlis
Roy H
RH
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Fijal
Bonnie
B
Dharia
Sweta
S
Heinloth
Alexandra N
AN
Houston
John P
JP
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride