Clinical trial NCT01902004: Brain Aging and Treatment Response in Geriatric Depression
Official title: Treatment of Geriatric Depression With Mild Cognitive Impairment: A Double-blind Placebo-Controlled Trial of Namenda (Memantine) Augmentation of Lexapro (Escitalopram) in Depressed Patients at Least 60 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Mild Cognitive Impairment (MCI)
Depression
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
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2013-07-17
Enrollment: 115
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Hamilton Depression Rating Scale
timeFrame: Measured at 3 months; 6 months and 12 months
Secondary outcomes:
measure: Change in Montgomery Asberg Depression Rating Scale
timeFrame: Measured at 3 months; 6 months and 12 months
measure: Change in Cognitive Domain Scores
timeFrame: Measured at 6 months and 12 months
Other outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Measured at 3, 6 months and 12 months
Locations:
city: Los Angeles
country: United States
facility: UCLA Semel Institute - Neuropsychiatric Institute (NPI)
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Helen Lavretsky, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kilpatrick LA, Krause-Sorio B, Siddarth P, Narr KL, Lavretsky H. Default mode network connectivity and treatment response in geriatric depression. Brain Behav. 2022 Apr;12(4):e2475. doi: 10.1002/brb3.2475. Epub 2022 Mar 1.
citation: Krause-Sorio B, Siddarth P, Kilpatrick L, Laird KT, Milillo MM, Ercoli L, Narr KL, Lavretsky H. Combined treatment with escitalopram and memantine increases gray matter volume and cortical thickness compared to escitalopram and placebo in a pilot study of geriatric depression. J Affect Disord. 2020 Sep 1;274:464-470. doi: 10.1016/j.jad.2020.05.092. Epub 2020 May 24.
citation: Grzenda A, Siddarth P, Laird KT, Yeargin J, Lavretsky H. Transcriptomic signatures of treatment response to the combination of escitalopram and memantine or placebo in late-life depression. Mol Psychiatry. 2021 Sep;26(9):5171-5179. doi: 10.1038/s41380-020-0752-2. Epub 2020 May 7.
citation: Lavretsky H, Laird KT, Krause-Sorio B, Heimberg BF, Yeargin J, Grzenda A, Wu P, Thana-Udom K, Ercoli LM, Siddarth P. A Randomized Double-Blind Placebo-Controlled Trial of Combined Escitalopram and Memantine for Older Adults With Major Depression and Subjective Memory Complaints. Am J Geriatr Psychiatry. 2020 Feb;28(2):178-190. doi: 10.1016/j.jagp.2019.08.011. Epub 2019 Aug 22.