RCT of Brain Longitudinal Biomarker Study (OPT-Neuro RCT)

Inclusion Criteria: * Men and women aged 60 and older, with approximately equal proportions aged 60-70 and 70+. * Current Major Depressive Disorder (MDD), single or recurrent, as diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. * Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length (approximately 12 weeks). * PHQ-9 score of 10 or higher. Exclusion Criteria: * Dementia; patients screened out due to possible dementia will be referred to a local Memory Clinic or back to their clinician for evaluation to clarify the presence or absence of dementia. * Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms. * High risk for suicide (e.g. active Suicidal ideations (SI) and or current/recent intent or plan)). Urgent psychiatric referral will be made in these cases. * Non-correctable, clinically significant sensory impairment (e.g., cannot hear well enough to cooperate with interview). * Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. * Moderate to severe substance or alcohol use disorder, as determined by study physician. * Seizure disorder. * Parkinson's Disease