Major Depressive Disorder
Conditions
Keywords
major depression, major depressive disorder, MDD, escitalopram, brexpiprazole, neuroimaging, genomics, proteomics, metabolomics
Brief summary
This is a study that will test a predictive biomarker algorithm based on results from a previous study. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE).
Detailed description
This is a multi-site, randomized study with two treatment phases: a double-blind primary treatment phase of 8 weeks, and an open-label secondary extension phase of 4 weeks. This study aims to test a predictive biomarker algorithm to select medication treatment for patients with major depressive disorder (MDD) based on results from the recently completed Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures from both MDD patients and healthy controls. This is not a study to evaluate efficacy of medications; medications in this study have been approved by Health Canada and are widely used for the treatment of MDD. In this study, individuals diagnosed with MDD in a current major depressive episode (MDE) will be randomly assigned to one of the two treatment groups: Personalized Assignment group or Random Assignment group. Patients in the Random Assignment group will randomly receive open-label escitalopram with the addition of either blinded placebo or brexpiprazole for 8 weeks. Patients in the Personalized Assignment group will receive open-label escitalopram with the addition of either placebo or blinded brexpiprazole for 8 weeks depending on what the predictive biomarker algorithm suggests. At Week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). All patients who initially received both open-label escitalopram and blinded brexpiprazole (regardless of treatment group) will continue to receive these medications for another 4 weeks but the brexpiprazole will no longer be blinded. For those patients who initially received open-label escitalopram and blinded placebo (regardless of treatment group), nonresponders will receive open-label escitalopram and open-label brexpiprazole for another 4 weeks and responders will receive open-label escitalopram only for another 4 weeks. Over the 12 weeks, participants will attend 7 study visits where they will complete clinical assessments (clinician administered and self-report) and cognitive tests; provide blood, urine, and stool samples; undergo neuroimaging procedures (MRI and EEG); and provide speech samples. At the end of the study, modeling methods will be used to integrate data from these measures to determine the features that best predict treatment outcome.
Interventions
DRUGEscitalopram
All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).
DRUGBrexpiprazole
Depending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders.
Sponsors
Nova Scotia Health Authority
Unity Health Toronto
Centre for Addiction and Mental Health
McMaster University
Queen's University
University of Ottawa
University of British Columbia
University of Calgary
McGill University
Dalhousie University
University of Michigan
Simon Fraser University
Ontario Shores Centre for Mental Health Sciences
University of Saskatchewan
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Patients Inclusion Criteria: * Outpatients 18 to 65 years of age. * Meet DSM-5 criteria for MDE in MDD as determined by SCID-5. * Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 (exceptions: stable use of hypnotics; stable use of stimulants for attention-deficit/hyperactive disorder). * MADRS score ≥ 24. * Fluency in English, sufficient to complete the interviews and self-report questionnaires.
Exclusion criteria
* Any 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 4 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 or brexpiprazole, and patients at risk for hypomanic switch (i.e. with a history of antidepressant induced hypomania). Healthy Comparison (HC) Participants Inclusion Criteria: * 18 to 65 years of age. * No history of psychiatric disorders (as determined by SCID-5) or significant physical conditions (e.g. arthritis, fibromyalgia). * Fluency in English, sufficient to complete the interviews and self-report questionnaires.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline | Baseline to Week 8 | Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response | Baseline to Week 8 | Defined as a decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit |
| Time to clinical response | Baseline to Week 8 | Defined as time (i.e., number of weeks) to achieve clinical response (i.e., decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit) |
| Remission at Week 8 | Week 8 | Defined as MADRS score ≤10 at Week 8 |
Countries
Canada
Contacts
CONTACTJessica B Toombs, MSc
CONTACTNicole M Stinson, BSc
PRINCIPAL_INVESTIGATORRudolf Uher, MD, PhD
Nova Scotia Health Authority
Outcome results
None listed