Phase 3 N=35 Treatment

Memantine Plus Es-citalopram in Elderly Depressed Patients With Cognitive Impairment

Mild Cognitive Impairment · Major Depressive Disorder · Alzheimer's Disease

Bottom Line

View on ClinicalTrials.gov: NCT01876823 ↗

Enrolled (actual)

Serious AEs

5.7%

Results posted

Oct 2014

Primary outcome: Primary: Change in Selective Reminding Test - Total Immediate Recall (SRT-IR) — 7.5 units on a scale

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: es-citalopram (Drug); Memantine (Drug)
Age: Adult, Older Adult · 50+ yrs
Sex: All
Sponsor: New York State Psychiatric Institute
Primary completion: Mar 2010

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Selective Reminding Test - Total Immediate Recall (SRT-IR)	7.5	—
SECONDARY Change in Wechsler Memory Scale-III (WMS-III)	9.9	—
SECONDARY Change in Selective Reminding Test - Delayed Recall (SRT-DR)	1.2	—
SECONDARY Change in Trails B	-36.3	—
SECONDARY Change in Trails A	1.9	—

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.

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):

Selective Reminding Test with delay Wechsler Memory Scale (WMS): Visual Reproduction - with delay, % savings from immed to delay Controlled Oral Word Association Test Trails B Digit symbol subtest of Wechsler Adult Intelligence Scale (WAIS)-III Continuous Performance Test iii. CGI for severity of Cognitive deficit greater than 2 (absolute score on a 7-point scale:1=no deficit to 7=severe deficit). iv. Clinical Dementia Rating (CDR) = 0 or 0.5

Willing and capable of giving informed consent

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.
Patient with a history of non-response to Citalopram or es-citalopram

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01876823). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.