International Study to Predict Optimized Treatment - Depression: iSPOT-D
About iSPOT-D

Why depression?

Worldwide, major depressive disorder (MDD) is the leading cause of disability and lost productivity (Whiteford et al., 2013). Over 60 million Americans will gain improved mental health insurance coverage under the Affordable Care Act and a further 50 million will do so under recent Medicare reforms.

Despite this high prevalence and enormous impact of MDD, we still do not understand the cause of MDD and treatments continue to rely on trial-and-error processes.

iSPOT-D and Biomarkers 

iSPOT-D is currently the largest biomarker study for MDD, aimed at improving treatment outcomes for MDD. The 20 sites contributing to iSPOT-D span 5 countries. Dr. Leanne Williams was the academic lead investigator for iSPOT-D. Her role spanned these sites, and also spanned the design, implementation, recruitment and publication planning phases of the study (2008 – 2013).

Our aim
Our aim is to improve outcomes for depression. iSPOT-D is about personalized neuroscience. Since we currently do not know who is likely to respond to which treatment, iSPOT-D is designed to test how each individual person’s brain function and genetics are matched to commonly used treatments. We can then discover which biomarkers (or combination of biomarkers) predict which people respond to treatments and which people do not.

What is involved? 

We are assessing outcomes for 3 commonly used antidepressants (Escitalopram, Venlafaxine, Sertraline).  

Clinical measures are combined with multiple biomarkers:

  • Computerized behavioral tests of cognition and emotion
  • Physiological measures such as event related potentials (ERPs)
  • Brain imaging measures such as functional MRI
  • A blood sample for genotyping

Who is taking part?

A total of 2,016 adult patients meeting DSM-IV criteria for MDD (nonpsychotic) and 672 age and sex-matched healthy controls will participate in this international, multi-site study. Approximately 10% of participants complete brain imaging sessions at the Sydney or Stanford sites. Participants are first tested prior to medication. At the end of this testing session, patients are given a letter addressed to their treating clinician with their randomized medication. After 8 weeks, participants return for on-medication testing. We also undertake a total of 8 short phone call interviews at assess their symptoms (day 4, week 2, week 4, week 6, week 12, week 16, week 24, and week 52).

Each patient’s referring doctor will be sent a detailed, evidence-based off and on medication report comparing their patient’s performance on the clinical interview (depression diagnosis and severity), symptoms and cognitive test battery compared to age and sex-matched controls. Participants who complete the MRI scan will also receive an MRI report. Results can be used as part of the doctor’s assessment of treatment response.

iSPOT-D Registration and Sponsor

Sponsor:  Brain Resource Company Operations Pty Ltd. 
Registry Name:
Registration Number: NCT00693849
Clinical Trials site link can be found 
here .

More about the protocol and measures can be found in these papers:

Williams LM, Rush AJ Koslow SH, Wisniewski SR, Cooper N, Nemeroff CB, Schatzberg AF, Gordon E. International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol. Trials, 2011.  Link here .

Grieve SM, Korgaonkar MS, Etkin A, Harris AWF, Koslow SH, Wisniewski S, Schatzberg AF, Nemeroff CB, Gordon E, Williams LM. Brain imaging predictors and the International Study to Predict Optimized Treatment for Depression, a randomized controlled trial. Trials, 2013. 
Link here .

Some of the first results are in these papers:

Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., Williams, L. M. Using Standardized fMRI Protocols to Identify Patterns of Prefrontal Circuit Dysregulation that are Common and Specific to Cognitive and Emotional Tasks in Major Depressive Disorder: First Wave Results from the iSPOT-D Study. Neuropsychopharmacology. 2013; 38 (5): 863-871.  Link here .

Grieve, S. M., Korgaonkar, M. S., Koslow, S. H., Gordon, E., Williams, L. M. Widespread reductions in gray matter volume in depression. NeuroImage. Clinical. 2013; 3: 332-339. 
Link here .

Korgaonkar, M. S., Cooper, N. J., Williams, L. M., Grieve, S. M. Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: a whole-brain diffusion tensor imaging tractography study. Neuroreport. 2012; 23 (9): 566-571. 
Link here .

Korgaonkar, M. S., Grieve, S. M., Koslow, S. H., Gabrieli, J. D., Gordon, E., Williams, L. M. Loss of White Matter Integrity in Major Depressive Disorder: Evidence Using Tract-Based Spatial Statistical Analysis of Diffusion Tensor Imaging. Human Brain Mapping. 2011; 32 (12): 2161-2171. 
Link here .