Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression

Inclusion Criteria: * Age \> 60 years * Diagnosis of major depressive disorder, single or recurrent episode (DSM5) * Symptom Severity: MADRS ≥ 15 * Seeking antidepressant treatment * Cognition score of MoCA \>24 * Fluent in English or Spanish Exclusion Criteria: * Other Axis I psychiatric disorders, except for simple phobia or anxiety disorders present uniquely during the depressive episode (e.g., generalized anxiety disorder (GAD) or panic disorder symptoms) * History of alcohol or drug dependence or abuse in the last year * History of a developmental disorder or history of IQ (intelligence quotient) \<70 * Acute suicidality ideation within the past month as determined by the Columbia Suicide Severity Rating Scale (C-SSRS) * Acute grief (\<1 month) * Current or past psychosis * Primary neurological disorder, including dementia, clinical stroke, brain tumor, epilepsy, etc. * Presence of unstable medical illness requiring urgent treatment * Any MRI contraindication * Electroconvulsive Therapy (ECT) in last 6 months