Canadian Biomarker Integration Network for Depression Study (CAN-BIND)

• MADRS (Montgomery-Asberg Depression Rating Scale) [ Time Frame: Week 8, Week 16 ] [ Designated as safety issue: No ]
  Clinical response (≥ 50% reduction in MADRS scores from baseline)
• Integrated Biomarker Predictors of Response [ Time Frame: Week 2; Week 2 minus Week 0 ] [ Designated as safety issue: No ]
  Integrated data from clinical, neuroimaging and molecular modalities

This study is a pilot to assess feasibility of the protocol in patients and controls across six participating sites. The goal is to identify biological markers (biomarkers)that can be measured at baseline or early in treatment to predict treatment outcome in individual patients with Major Depressive Disorder (MDD). Biomarkers of interest will be clinical (using interview and self-report measures), molecular (from blood samples) and neurobiological (using neuroimaging and EEG).

This is a study to collect clinical and biomarker data which will be used to build models to predict treatment response. This is not a study to evaluate efficacy of medications, as medications in this study have been approved by Health Canada and are widely used for the treatment of Major Depressive Disorder.

This is an open label study - patients with a diagnosis of MDD and a current major depressive episode will be treated with 10-20mg of escitalopram for the first 8 weeks. At week 8, patients will be assessed for medication response (response is defined as ≥ 50% reduction in MADRS scores from baseline).

Non-responders will receive open label treatment with either aripiprazole or quetiapine as an add-on treatment while responders will continue on escitalopram until study endpoint. Healthy controls will not receive any medication over the course of the trial.

There are approximately 7 clinic visits over a 16 week period during which patients and healthy controls will undergo clinician administered scales and self reports, provide blood and urine samples (which will undergo proteomic and genomic analyses) as well as neuroimaging (fMRI and EEG).

At the end of the study, mathematical modeling methods will be used to integrate the data from the various modalities to see which features best predict treatment outcome.

• Drug: escitalopram
  Patients will be given escitalopram for the first 8 weeks of the trial. At week 8, patients who are assessed as 'responders' will continue on escitalopram until study endpoint.
  Other Name: Cipralex
• Drug: Aripiprazole
  At Week 8, patients assessed as 'non-responders' will be given either aripiprazole or quetiapine as an add-on treatment to escitalopram.
  Other Name: Abilify
• Drug: Quetiapine
  Other Names:

  • At Week 8, patients assessed as 'non-responders' will be given either aripiprazole or quetiapine as an add-on treatment to escitalopram.
  • --------------------------------------------------------------------------------

• Active Comparator: Escitalopram
  Patients are on escitalopram for 8 weeks. At Week 8, patients will be assessed as 'responders' or 'non-responders'. 'Responders' will continue on escitalopram until study endpoint.
  Intervention: Drug: escitalopram
• Active Comparator: non-responders - A
  At Week 8, patients assessed as 'non-responders' will be given either aripiprazole or quetiapine as an add-on treatment to escitalopram.
  Intervention: Drug: Aripiprazole
• Active Comparator: Non-responders - Q
  At Week 8, patients assessed as 'non-responders' will be given either aripiprazole or quetiapine as an add-on treatment to escitalopram.
  Intervention: Drug: Quetiapine

Inclusion Criteria:

• Outpatients who are 18-55 years of age
• Meet DSM-IV-TR criteria for Major Depressive Episode in Major Depressive Disorder by the MINI
• Episode duration ≥ 3 months
• Free of psychotropic medications for at least 5 half-lives (i.e. 1 week for antidepressants, 5 weeks for fluoxetine) before baseline Visit 1
• MADRS ≥ 24
• Fluency in English, sufficient to complete the interviews and self-report questionnaires

Exclusion Criteria:

• Any Axis I diagnosis other than MDD that is considered the primary diagnosis
• Bipolar I or Bipolar II diagnosis
• Presence of a significant Axis II diagnosis (borderline, antisocial)
• High suicidal risk, defined by clinician judgment
• Substance dependence/abuse in the past 6 months
• Presence of significant neurological disorders, head trauma or other unstable medical conditions
• Pregnant or breastfeeding
• Failure of 3 or more adequate pharmacologic interventions (as determined by the Antidepressant Treatment History Form)
• Started psychological treatment within the past 3 months with the intent of continuing treatment
• Patients who have previously failed escitalopram or showed intolerance to escitalopram and patients at risk for hypomanic switch (i.e. with a history of antidepressant hypomania)

• University of Toronto
• University of Calgary
• University of British Columbia
• McGill University
• Queen's University
• Centre for Addiction and Mental Health
• McMaster University