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J Psychiatr Res. 2016 Jul;78:11-23. doi: 10.1016/j.jpsychires.2016.03.001. Epub 2016 Mar 15.

Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design.

Author information

1
University of Texas, Southwestern Medical Center, Dallas, TX, USA. Electronic address: madhukar.trivedi@utsouthwestern.edu.
2
New York State Psychiatric Institute & Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
3
Massachusetts General Hospital, Boston, MA, USA.
4
Stony Brook University, Stony Brook, NY, USA.
5
University of Texas, Southwestern Medical Center, Dallas, TX, USA.
6
University of Pittsburgh, Pittsburgh, PA, USA.
7
Harvard Medical School - McLean Hospital, Boston, MA, USA.
8
Columbia University, New York, NY, USA.
9
Harvard University, Cambridge, MA, USA.
10
University of Michigan, Ann Arbor, MI, USA.
11
Stanford University, Stanford, CA, USA.
12
New York University, New York, NY, USA.

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.

CLINICAL TRIAL REGISTRATION:

Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC). Identifier: NCT01407094. URL: http://clinicaltrials.gov/show/NCT01407094.

KEYWORDS:

Antidepressant response; Biosignatures; EMBARC; Mediators; Moderators; Sertraline

PMID:
27038550
PMCID:
PMC6100771
DOI:
10.1016/j.jpsychires.2016.03.001
[Indexed for MEDLINE]
Free PMC Article

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