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Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial

Stuart M Grieve1234*, Mayuresh S Korgaonkar15, Amit Etkin67, Anthony Harris15, Stephen H Koslow89, Stephen Wisniewski7, Alan F Schatzberg6, Charles B Nemeroff8, Evian Gordon12 and Leanne M Williams156

Author Affiliations

1 The Brain Dynamics Centre, University of Sydney Medical School - Westmead and Westmead Millennium Institute, Sydney, NSW 2145, Australia

2 Brain Resource, Level 12, 235 Jones Street, Ultimo, Sydney, NSW 2007, Australia and Suite 200, 1000 Sansome Street, San Francisco, CA 94111, USA

3 Sydney Medical School, University of Sydney, Camperdown, NSW 2050, Australia

4 Department of Radiology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia

5 Discipline of Psychiatry, University of Sydney Medical School: Western, Westmead Hospital, Sydney, NSW 2145, Australia

6 Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA 94305, USA

7 Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, USA

8 Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA

9 BRAINnet Foundation, 71 Stephenson Street, Suite 400, San Francisco, CA 94105, USA

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Trials 2013, 14:224  doi:10.1186/1745-6215-14-224

Published: 18 July 2013



Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD.


The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (nā€‰=ā€‰102), test the findings in the second half, and then extend the analyses to the total sample.

Trial registration

International Study to Predict Optimized Treatment - in Depression (iSPOT-D)., NCT00693849.

Major depressive disorder; Antidepressant treatments; Imaging; Biomarker; iSPOT-D