title: Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design.
abstract: Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (≤30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository.
  
  
  
  Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC). Identifier: NCT01407094. URL: http://clinicaltrials.gov/show/NCT01407094.
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA. Electronic address: madhukar.trivedi@utsouthwestern.edu.
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.affiliation: New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McGrath
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Benji T
authors.initials: BT
authors.lastname: Kurian
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
authors.affiliation: New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Bruder
authors.affiliation: Harvard Medical School - McLean Hospital, Boston, MA, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Pizzagalli
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Toups
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Cooper
authors.affiliation: New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Adams
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weyandt
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Morris
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Grannemann
authors.affiliation: Columbia University, New York, NY, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.affiliation: Harvard University, Cambridge, MA, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Buckner
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Melvin
authors.initials: M
authors.lastname: McInnis
authors.affiliation: Stanford University, Stanford, CA, USA.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Kraemer
authors.affiliation: New York University, New York, NY, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Petkova
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carmody
authors.affiliation: New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018579:Patient Selection; D057285:Precision Medicine; D011569:Psychiatric Status Rating Scales; D011799:Quinazolines / Q000627:therapeutic use; D012107:Research Design; D020280:Sertraline / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D011799:Quinazolines; C012675:buquineran; D020280:Sertraline
keywords: Antidepressant response; Biosignatures; EMBARC; Mediators; Moderators; Sertraline