Brain Aging and Treatment Response in Geriatric Depression

Inclusion Criteria: * Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified) * Score of 16 or higher on the 24-item Hamilton Rating Scale for Depression (HDRS) at study entry * Score of 24 or higher on the Mini-Mental State Exam (MMSE) * Age 60 years old or older Exclusion Criteria: * History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode * Presence of psychotic symptoms * Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry * Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry * Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases * Toxic or metabolic abnormalities on laboratory examination * Medications taken or medical illnesses present that could account for depression * Active heart failure categorized as Class III or greater according to New York Heart Association criteria * Heart attack or crescendo angina within the 3 months prior to study entry * Symptomatic cardiac arrhythmias or symptomatic, hemodynamically significant mitral or aortic valvular disease * Resting heart rate less than 50 beats per minute and a corrected QT (QTc) interval greater than 0.45 seconds * Second or third degree atrioventricular block * Systolic blood pressure greater than 180 mmHg or less than 90 mmHg and diastolic blood pressure greater than 105 mmHg or less than 50 mmHg at study entry * Treated with depot neuroleptic therapy within 6 months prior to study entry * Treated with any neuroleptic, antidepressant, anxiolytic medication (other than lorazepam), or over-the-counter CNS-active medications used for treatment of depression (e.g, St. John's Wort, kava-kava, melatonin) within 2 weeks (4 weeks for fluoxetine or monoamine-oxidase inhibitors \[MAOIs\]) prior to the first administration of study medication * Known allergy to escitalopram or memantine or history of ineffective treatment with escitalopram or memantine for current depressive episode * Requires concomitant therapy with any prescription or over-the-counter medications that have potentially dangerous interactions with either escitalopram or memantine * Requires electroconvulsive therapy (ECT) or received ECT within 3 months prior to study entry * Initiated psychotherapy within 3 months prior to study entry or will be initiating or terminating psychotherapy during the study