Brain Aging and Treatment Response in Geriatric Depression
Condition: Mild Cognitive Impairment (MCI); Depression
MeSH terms: Depression; Depressive Disorder; Cognitive Dysfunction
Intervention: Escitalopram; Memantine; Placebo
Intervention description: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion.; Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.; Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
Intervention MeSH terms: Memantine; Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 115.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Major Depression; Geriatric Major Depression; Executive Cognitive Dysfunction; Mild Cognitive Impairment; Older Adults; Geriatric; Executive Cognitive Impairment; Quality of Life; Disability; Comorbidity; Medical Burden; Safety; Candidate Genes

Summary:

      The proposed project will evaluate the role of neuroimaging biomarkers of brain aging (i.e.,
      neurodegenerative and vascular brain changes) and mild cognitive impairment in the patterns
      of treatment response to memantine combined with escitalopram compared to escitalopram and
      placebo.
    

Eligibility criteria:

        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