Brief Report| Volume 67, ISSUE 11, P1110-1113, June 01, 2010

Download started.


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


      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.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Franchini L.
        • Serretti A.
        • Gasperini M.
        • Smeraldi E.
        Familial concordance of fluvoxamine response as a tool for differentiating mood disorder pedigrees.
        J Psychiatr Res. 1998; 32: 255-259
        • Bozina N.
        • Peles A.M.
        • Sagud M.
        • Bilusic H.
        • Jakovljevic M.
        Association study of paroxetine therapeutic response with SERT gene polymorphisms in patients with major depressive disorder.
        World J Biol Psychiatry. 2008; 9: 190-197
        • Garriock H.A.
        • Kraft J.B.
        • Peters E.J.
        • Jenkins G.D.
        • Reinalda M.S.
        • McGrath P.J.
        • et al.
        Receptor is associated with response to antidepressant treatment.
        2008 (Presented at the 7th Annual Pharmacogenetics in Psychiatry Meeting, April 4–5, 2008, New York, NY)
        • Kraft J.B.
        • Slager S.L.
        • McGrath P.J.
        • Hamilton S.P.
        Sequence analysis of the serotonin transporter and associations with antidepressant response.
        Biol Psychiatry. 2005; 58: 374-381
        • Lesch K.P.
        • Gutknecht L.
        Pharmacogenetics of the serotonin transporter.
        Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 1062-1073
        • Mrazek D.A.
        • Rush A.J.
        • Biernacka J.M.
        • O'Kane D.J.
        • Cunningham J.M.
        • Wieben E.D.
        • et al.
        SLC6A4 variation and citalopram response.
        Am J Med Genet B Neuropsychiatr Genet. 2009; 150B: 341-351
        • Nikisch G.
        • Eap C.B.
        • Baumann P.
        Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: A pilot study.
        Pharmacol Rev. 2008; 58: 344-347
        • Paddock S.
        • Laje G.
        • Charney D.
        • Rush A.J.
        • Wilson A.F.
        • Sorant A.J.
        • et al.
        Association of GRIK4 with outcome of antidepressant treatment in the STAR* D cohort.
        Am J Psychiatry. 2007; 164: 1181-1188
        • Uhr M.
        • Tontsch A.
        • Namendorf C.
        • Ripke S.
        • Lucae S.
        • Ising M.
        • et al.
        Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression.
        Neuron. 2008; 57: 203-209
        • Wong M.L.
        • Whelan F.
        • Deloukas P.
        • Whittaker P.
        • Delgado M.
        • Cantor R.M.
        • et al.
        Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response.
        Proc Natl Acad Sci U S A. 2006; 103: 15124-15129
        • Kraft P.
        Curses—winner's and otherwise—in genetic epidemiology.
        Epidemiology. 2008; 19: 649-651
        • Whitmyer V.G.
        • Dunner D.L.
        • Kornstein S.G.
        • Meyers A.L.
        • Mallinckrodt C.H.
        • Wohlreich M.M.
        • et al.
        A comparison of initial duloxetine dosing strategies in patients with major depressive disorder.
        J Clin Psychiatry. 2007; 68: 1921-1930
        • Serretti A.
        • Kato M.
        • Kennedy J.L.
        Pharmacogenetic studies in depression: A proposal for methodologic guidelines.
        Pharmacogenomics J. 2008; 8: 90-100
        • Perlis R.
        • Fijal B.
        • Adams D.
        • Sutton V.
        • Trivedi M.
        • Houston J.
        Variation in catechol-O-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder.
        Biol Psychiatry. 2009; 65: 785-791
        • Jurinke C.
        • van den Boom D.
        • Cantor C.R.
        • Koster H.
        Automated genotyping using the DNA MassArray technology.
        Methods Mol Biol. 2002; 187: 179-192
        • Owens M.J.
        • Morgan W.N.
        • Plott S.J.
        • Nemeroff C.B.
        Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites.
        J Pharmacol Exp Ther. 1997; 283: 1305-1322
        • Arias B.
        • Catalan R.
        • Gasto C.
        • Gutierrez B.
        • Fananas L.
        5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a 12-weeks follow up study.
        J Clin Psychopharmacol. 2003; 23: 563-567
        • Durham L.K.
        • Webb S.M.
        • Milos P.M.
        • Clary C.M.
        • Seymour A.B.
        The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder.
        Psychopharmacology. 2004; 174: 525-529
        • Perlis R.H.
        • Mischoulon D.
        • Smoller J.W.
        • Wan Y.J.
        • Lamon-Fava S.
        • Lin K.M.
        • et al.
        Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment.
        Biol Psychiatry. 2003; 54: 879-883