title: Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.
abstract: The purpose of this study was to determine whether the baseline metabolic profile (that is, metabotype) of a patient with major depressive disorder (MDD) would define how an individual will respond to treatment. Outpatients with MDD were randomly assigned to sertraline (up to 150 mg per day) (N=43) or placebo (N=46) in a double-blind 4-week trial. Baseline serum samples were profiled using the liquid chromatography electrochemical array; the output was digitized to create a 'digital map' of the entire measurable response for a particular sample. Response was defined as ≥50% reduction baseline to week 4 in the 17-item Hamilton Rating Scale for Depression total score. Models were built using the one-out method for cross-validation. Multivariate analyses showed that metabolic profiles partially separated responders and non-responders to sertraline or to placebo. For the sertraline models, the overall correct classification rate was 81% whereas it was 72% for the placebo models. Several pathways were implicated in separation of responders and non-responders on sertraline and on placebo including phenylalanine, tryptophan, purine and tocopherol. Dihydroxyphenylacetic acid, tocopherols and serotonin were common metabolites in separating responders and non-responders to both drug and placebo. Pretreatment metabotypes may predict which depressed patients will respond to acute treatment (4 weeks) with sertraline or placebo. Some pathways were informative for both treatments whereas other pathways were unique in predicting response to either sertraline or placebo. Metabolomics may inform the biochemical basis for the early efficacy of sertraline.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA. rima.kaddurahdaouk@duke.edu
authors.forename: R
authors.initials: R
authors.lastname: Kaddurah-Daouk
authors.forename: S H
authors.initials: SH
authors.lastname: Boyle
authors.forename: W
authors.initials: W
authors.lastname: Matson
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: S
authors.initials: S
authors.lastname: Matson
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: M B
authors.initials: MB
authors.lastname: Bogdanov
authors.forename: E
authors.initials: E
authors.lastname: Churchill
authors.forename: R R
authors.initials: RR
authors.lastname: Krishnan
authors.forename: A J
authors.initials: AJ
authors.lastname: Rush
authors.forename: E
authors.initials: E
authors.lastname: Pickering
authors.forename: M
authors.initials: M
authors.lastname: Delnomdedieu
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D020280:Sertraline / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline