Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)

Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)

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).

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.

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.