Treatment Resistant Geriatric Depression in Primary Care
This study involves collaboration between McLean Hospital, Geriatric Medicine at the Cambridge Health Alliance (CHA) and other sites within the Partners and Harvard Medical School network. The investigators plan to recruit individuals 55 to 89 years old with treatment resistant depression. Someone with "treatment resistant" depression for this study may be someone who still has sad or low feelings and thoughts even though he/she is taking an antidepressant medication for at least 8 weeks to help relieve his/her depression. During the study, subjects will gradually add memantine hydrochloride in dosages up to 20 mg/day for 8 weeks to their standard antidepressant treatment.
The investigators are doing this research study to help answer 3 questions:
- Do older adults with treatment resistant Major Depression have lower levels of a chemical in the brain called NAAG than older adults without Major Depression?
- Do older adults with naturally low NAAG levels do better on memantine hydrochloride treatment than older adults with higher amounts of this chemical on memantine hydrochloride treatment?
- Do older adults with treatment resistant depression have more problems with memory and concentration than older adults without depression?
The investigators are also interested in looking at electrical and neuronal activity of the brain, spiritual beliefs, and fatigue in relationship to depression.
The investigators hypothesize that:
- Older individuals with treatment resistant Major Depression will have lower levels of NAAG compared with age-matched older control subjects.
- Older adults with treatment resistant depression and low NAAG levels will do better on treatment with memantine hydrochloride than older adults on memantine with higher NAAG levels.
- Older adults with depression will do better on tests of attention and executive functioning after treatment with memantine hydrochloride.
- Healthy controls will do better on tests of attention and executive functioning than older adults with depression.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Treatment Resistant Geriatric Depression in Primary Care: Is NAAG (N-Acetylaspartylglutamate), Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) at 3 Tesla, a Predictor of Treatment Response?|
- Mean Differences in NAAG Levels between Subject Groups at Baseline and Week 8 [ Time Frame: Baseline / Study Entry ] [ Designated as safety issue: No ]Are NAAG levels are lower in older adults with treatment resistant depression compared with healthy age-matched controls?
- Relationship of NAAG Levels and MADRS Scores between Subject Groups at Baseline and Week 8 [ Time Frame: 8-week trial ] [ Designated as safety issue: No ]Do subjects with low NAAG levels within the treatment resistant depression group prior to memantine hydrochloride augmentation respond better to treatment with memantine hydrochloride?
- Cognitive Impairment between Subject Groups at Baseline and Week 8 [ Time Frame: 8-week trial ] [ Designated as safety issue: No ]Do older adults with Major Depression have evidence of cognitive impairment (in particular in the realm of executive functioning and attention) compared with older healthy controls from baseline to study endpoint?
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||December 2016|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Memantine hydrochloride
Older individuals with DSM IV TR Major Depression, with persistent symptoms of depression despite at least 8 weeks of treatment with standard pharmacotherapy, will be referred for a study of memantine hydrochloride augmentation. Healthy control subjects follow similar study schedule for baseline and endpoint but do not receive memantine hydrochloride.
Dosing Form: Tablet
Dosage: 5mg, 10 mg
Memantine hydrochloride (Namenda®), a low to moderate affinity uncompetitive (open-channel) NMDA antagonist, is manufactured and supplied by Forest Laboratories, Incorporated. Only the subjects in the depression group will receive the study drug memantine HCl. Per psychiatrist's instructions, subjects may remain on the maximum dosage of memantine HCl allowed by the study protocol for a given week, or reduce the dosage if concerns regarding tolerability arise. The dosage of memantine HCl cannot be increased more rapidly than the dosing schedule listed below.
Memantine HCl Dosing Schedule:
5 mg qAM week 1 5 mg qAM and 5 mg qHS for week 2 10 mg qAM and 5 mg qHS for week 3 10 mg BID for week 4, 5, 6, 7, and 8
Other Name: Namenda (NDA # 021487)
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01392287
|United States, Massachusetts|
|Belmont, Massachusetts, United States, 02478|
|Principal Investigator:||Brent P Forester, M.D.||Mclean Hospital|