title: Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder: the result of two pooled RCTs.
abstract: Pharmacogenetics may allow for a personalized treatment, but a combination with clinical variables may further enhance prediction. In particular, in the present paper, we investigated early partial improvement (EPI) defined as 20% or more improvement by rating scales 2  weeks after treatment, in combination with selected gene variants as a predictor of treatment outcome in patients with major depressive disorder. Two randomized controlled trials with 168 Japanese depressed patients were used. A stepwise multiple linear regression model with HAM-D score change at week 6 as the dependent variable and genotypes, EPI, baseline HAM-D score, age and sex as independent variables was performed in paroxetine, fluvoxamine and milnacipran, respectively, to estimate the prediction of HAM-D change at week 6. In the paroxetine sample, only EPI (P<0.001) was significantly associated with HAM-D change (n=81, R(2)=0.25, P<0.001). In the fluvoxamine sample, 5-HTTLPR La/Lg, S (P=0.029), FGF2 rs1449683C/T (P=0.013) and EPI (P=0.003) were associated with HAM-D change (n=42, R(2)=0.43, P<0.001). In the milnacipran sample, HTR-1A-1019C/G (P=0.001), ADRA2A-1297C/G (P=0.028) and EPI (P<0.001) were associated with outcome (n=45, R(2)=0.71, P<0.001). EPI in combination with genetic variants could be a useful predictor of treatment outcome and could strengthen the practical use of pharmacogenetic data in clinical practice.
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Serretti
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nonen
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: Y
authors.identifier: 0000000324354033
authors.initials: Y
authors.lastname: Takekita
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Wakeno
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Azuma
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000367:Age Factors; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D003521:Cyclopropanes / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics; D016666:Fluvoxamine / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D017374:Paroxetine / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: C547768:ADRA2A protein, human; D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D003521:Cyclopropanes; C416003:FGF20 protein, human; C583518:HTR1A protein, human; D018341:Receptors, Adrenergic, alpha-2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D017374:Paroxetine; D005346:Fibroblast Growth Factors; D000078764:Milnacipran; D016666:Fluvoxamine