TY - JOUR
T1 - Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC)
T2 - Rationale and design
AU - Trivedi, Madhukar H.
AU - McGrath, Patrick J.
AU - Fava, Maurizio
AU - Parsey, Ramin V.
AU - Kurian, Benji T.
AU - Phillips, Mary L.
AU - Oquendo, Maria A.
AU - Bruder, Gerard
AU - Pizzagalli, Diego
AU - Toups, Marisa
AU - Cooper, Crystal
AU - Adams, Phil
AU - Weyandt, Sarah
AU - Morris, David W.
AU - Grannemann, Bruce D.
AU - Ogden, R. Todd
AU - Buckner, Randy
AU - McInnis, Melvin
AU - Kraemer, Helena C.
AU - Petkova, Eva
AU - Carmody, Thomas J.
AU - Weissman, Myrna M.
N1 - Funding Information:
The EMBARC study was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (Trivedi, M.H.) and U01MH092250 (McGrath, P.J., Parsey, R.V., Weissman, M.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Valeant Pharmaceuticals donated the Wellbutrin XL used in the study. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center, Madhukar H. Trivedi, M.D., Coordinating PI, and the Data Center at Columbia and Stony Brook Universities.
Funding Information:
This study was supported in part by Valeant Pharmaceuticals who donated the Wellbutrin XL used in this study. We would also like to thank the EMBARC National Coordinating Center at UT Southwestern Medical Center, Madhukar H. Trivedi, M.D., Coordinating PI, and the Data Center at Columbia University. We also thank Carol A. Tamminga, M.D., Communities Foundation of Texas, Inc. Chair in Brain Science, and Chair, Department of Psychiatry, University of Texas Southwestern Medical Center for administrative support and Cassandra Hatt for assistance with manuscript preparation and submission.
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Antidepressant response
KW - Biosignatures
KW - EMBARC
KW - Mediators
KW - Moderators
KW - Sertraline
UR - http://www.scopus.com/inward/record.url?scp=84962220007&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962220007&partnerID=8YFLogxK
U2 - 10.1016/j.jpsychires.2016.03.001
DO - 10.1016/j.jpsychires.2016.03.001
M3 - Review article
C2 - 27038550
AN - SCOPUS:84962220007
SN - 0022-3956
VL - 78
SP - 11
EP - 23
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -