Brain Aging and Treatment Response in Geriatric Depression

Phase 4

Completed

Conditions: Mild Cognitive Impairment (MCI)
Depression

Interventions: Drug: Escitalopram
Drug: Memantine
Drug: Placebo

Registration Number: NCT01902004

Lead Sponsor: University of California, Los Angeles

Brief 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.

Detailed Description: This study is designed to conduct a double-blind placebo-controlled trial of Namenda (Memantine) as an augmentation to Lexapro (Escitalopram) in depressed older adults 60 years of age and older. Throughout the course of the study, the investigators anticipate screening about 400 subjects to recruit 134 participants in the first four years. This study will require that the subjects complete up to 20 (twenty) visits in 12 (twelve) months to the study site during their participation. The purpose of this study is to determine whether Namenda (memantine) when taken in combination with Lexapro (escitalopram), may improve the quality of treatment response by making it faster and more complete, and also by improving thinking and memory in comparison to Lexapro taken with a placebo. Enrolled subjects will be provided with 10-20 mg of escitalopram for 12 months, and concurrently randomly assigned to either memantine or placebo groups. The investigators will also examine the safety and tolerability (how well the treatment works and the side effects) of a combination of Namenda and Lexapro as compared to placebo and Lexapro in subjects with major depressive disorder and mild cognitive impairment who are at least 60 years of age. Memantine is likely to accelerate and enhance antidepressant response to escitalopram and improve cognitive performance. Subjects with amnestic mild cognitive impairment or biomarkers of brain aging at baseline are likely to have preferential response to the combination of memantine and escitalopram compared to escitalopram and placebo, thus identifying a more personalized treatment approach in the high-risk subgroups for poor clinical outcomes.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 115

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Escitalopram and Memantine	Escitalopram	Participants will take a combination of Escitalopram and Memantine for 12 months
Escitalopram and Memantine	Memantine	Participants will take a combination of Escitalopram and Memantine for 12 months
Escitalopram and placebo	Placebo	Participants will take a combination of Escitalopram and placebo for 12 months
Escitalopram and placebo	Escitalopram	Participants will take a combination of Escitalopram and placebo for 12 months

Primary Outcome Measures

Name	Time	Method
Change in Hamilton Depression Rating Scale	Measured at 3 months; 6 months and 12 months	Clinician administered scale measures severity of depressive symptoms. This measure includes 24 items. Response options vary item to item and include the following ranges: \[0-2\], \[0-3\], and \[0-4\]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range \[0-74\], higher scores representing more severe difficulties.

Secondary Outcome Measures

Name	Time	Method
Change in Montgomery Asberg Depression Rating Scale	Measured at 3 months; 6 months and 12 months	Clinician administered item scale measures severity of depressive symptoms. The 10 items are measured on a 7-point scale ranging from 0 to 6; creating a total range of 0-60. A score of 0 suggests absence of symptoms and higher scores represent greater severity of depression.Severity gradations for the MADRS have been proposed (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe). Treatment remission is defined as an endpoint total score ≤ 10.
Change in Cognitive Domain Scores	Measured at 6 months and 12 months	Neuropsychological battery of tests which included the following domains: learning, delayed recall, and executive functioning. Raw scores were transformed to z-scores for each test score of interest for each participant, and then averaged. These z-scores were averaged within each neuropsychological domain to produce composite scores and then averaged over all tests to calculate a global performance score. Higher scores are indicative of better performance.