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