Effects of Combined Memantine (Namenda) Plus Escitalopram (Lexapro) Treatment in Elderly Depressed Patients With Cognitive Impairment
Overview
- Phase
- Phase 2
- Intervention
- es-citalopram
- Conditions
- Mild Cognitive Impairment
- Sponsor
- New York State Psychiatric Institute
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in Selective Reminding Test - Total Immediate Recall (SRT-IR)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Alzheimer's disease (AD), the most common dementing disorder of later life, is a major cause of disability and death in the elderly. Although a number of theoretical causes exist, the etiology of AD is still unknown. Consequently, the focus of treatments has been palliative, designed to ameliorate AD symptoms. Recent efforts, however, have revealed some surprising data suggesting that cholinesterase inhibitors (AchEIs), used over the last decade, and recently released memantine (an N-methyl-D-aspartate (NMDA) receptor antagonist), may confer protection to neurons. Thus, they may offer a slowing of cognitive decline and/or improvement in behavioral symptoms associated with memory impairment.
Over the last decade, it has been well documented that mild cognitive impairment (MCI) increases the risk of conversion to AD and that coincident depression and MCI (Dep-MCI) further increases the risk 2 to 3 fold. The primary focus of this line of investigation is to treat the very high risk to dement patient population with Dep-MCI, before they develop AD, in the hopes of delaying AD onset.
Memantine had not been studied in DEP-MCI patients. Since treatment of these patients with combined antidepressant and AChEIs has been associated with cognitive improvement in pilot studies, we explore whether treatment of DEP-MCI with memantine in addition to antidepressant treatment would benefit cognitive performance and lead to a low rate of conversion to dementia. We evaluate the cognitive and antidepressant benefit of combined open-label es-citalopram and memantine treatment over 48 weeks in a DEP-CI sample.
Detailed Description
The study is conducted in a sample of 35 elderly (50-90 years old) outpatients who meet study inclusion criteria for depression (DEP) (DSM-IV criteria for major depression, dysthymic disorder, or depression NOS) and mild cognitive impairment (MCI; e.g. operationally defined as between "normal" and "dementia"), i.e., Dep-MCI. The research plan includes: i) Obtaining a baseline psychiatric and neuropsychological test profile, ii) If currently on an ineffective antidepressant, having a one week washout (3 weeks for fluoxetine), iii) A treatment trial beginning with a two-week es-citalopram lead-in period. At two weeks, memantine (Namenda) is added starting at 5 mg/day and increased until the maximum dose of 20 mg/day is reached by six weeks. The study psychiatrist administers: the 24-item Hamilton Depression Rating Scale (HAM-D); the Clinical Global Impression (CGI, 1-7 scale) initial severity and subsequent change ratings separately for depression, cognition, and overall clinical status; the Treatment Emergent Symptom Scale (TESS) for somatic side effects. A trained technician administers the neuropsychological battery at baseline, 12, 24 and 48 weeks. If the patient is an antidepressant non-responder during the first 12-weeks, the es-citalopram is changed to an alternative antidepressant, as clinically indicated by the treating psychiatrist. The patient remains on the memantine for the entire 48-weeks, irrespective of antidepressant response. This will tell us about the efficacy and tolerability of es-citalopram+memantine on both cognitive and depressive symptoms in Dep-MCI patients and will potentially have broader public health implications because Dep-MCI is a wide-spread clinical problem where management needs to be improved.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Of either sex, age greater than 49 years old
- •Meets criteria for both "depression" and "cognitive impairment".
- •Study Criteria for "depression":
- •i. Patients who meet DSM-IV criteria for Major Depression, Dysthymic Disorder, or Dysthymia symptoms criteria of minimum 6 month duration (not the 2 year DSM-IV criteria). ii. 24-item HAM-D greater than 13; and iii. Clinical Global Impression (CGI) for severity of Depression greater than 2 (absolute score at least mild to moderate depression on a 7-point scale)
- •Study Criteria for "cognitive deficit":
- •i. Subjective memory complaint ii.Mini Mental Status Exam (MMSE) greater than 24; and at least one of a, b, or c:
- •less than 3 on MMSE 5 min delay on recall
- •scores on 2 neuropsychological tests greater than 1 Standard Deviation (SD) below standardized norms, or
- •score on 1 neuropsychological tests greater than 2 SD below standardized norms.
- •Neuropsychological tests for inclusion criteria (subset of larger battery):
Exclusion Criteria
- •Meets Criteria for dementia (DSM-IV) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria (NINCDS-ADRDA criteria)
- •Meets criteria for:
- •schizophrenia
- •alcohol or substance dependence or abuse within the last 6 months.
- •Suicidal attempt in last 6 months or current suicidal intent.
- •Patients currently on an effective antidepressant medication
- •Use of cholinesterase inhibitors in the last year.
- •Neurological disease including stroke, epilepsy, or other neurodegenerative disorders.
- •An acute, severe or unstable medical condition such as metastatic or active cancer, hepatic disease, or primary renal disease requiring dialysis.
- •Patients who can not tolerate being tapered off antidepressant medication (i.e. greater than a 25% incr. in baseline HAM-D) or has a history indicating patient is unlikely to tolerate psychotropic washout.
Arms & Interventions
es-citalopram and Memantine Treatment
concurrent es-citalopram plus memantine were administered for 48 weeks.
Intervention: es-citalopram
es-citalopram and Memantine Treatment
concurrent es-citalopram plus memantine were administered for 48 weeks.
Intervention: Memantine
Outcomes
Primary Outcomes
Change in Selective Reminding Test - Total Immediate Recall (SRT-IR)
Time Frame: baseline, 48 weeks
Change in Selective Reminding Test-Total Immediate Recall (SRT-IR) scores from baseline to Week 48: Measures word recall (maximum 12 words per trial, across 6 trials). Maximum total recall score across 6 trials is 72; minimum recall is 0 across 6 trials. The higher the raw score, the better the patient did at recalling the target words. The unit of measure is the raw score, or the sum of the number of words recalled across all 6 trials.
Secondary Outcomes
- Change in Wechsler Memory Scale-III (WMS-III)(Baseline, Week 48)
- Change in Selective Reminding Test - Delayed Recall (SRT-DR)(Baseline, Week 48)
- Change in Trails B(Baseline, Week 48)
- Change in Trails A(Baseline, Week 48)