Post Hoc Evidence for an Additive Effect of Memantine and Donepezil: Consistent Findings from DOMINO-AD Study and
S Hendrix1, N Ellison, S Stanworth
1Suzanne Hendrix, Pentara Corporation, Salt Lake City, UT, USA, Telephone: ++1-801-898-724, Fax: ++1-801-486-7467, shendrix@pentaracorp.com.
Background:
Several randomized trials have demonstrated superiority of memantine-cholinesterase inhibitor combination therapy in patients with moderate to severe Alzheimer's disease, yet a recent publication reported no additional benefit of add-on memantine therapy compared to donepezil alone.
Objectives:
In this post hoc analysis, we sought to re-evaluate the results from the DOMINO study using common statistical tools and to apply the statistical models used in the DOMINO study to a pooled data set of 24- to 28-week randomized trials of memantine in patients with moderate to severe AD in order to explore the robustness of the primary findings from the DOMINO study.
Design:
DOMINO study: Randomized, double-blind, placebo-controlled trial (Current Controlled Trial number, ISRCTN49545035); Memantine Clinical Trial Program: Pooled analysis from four randomized, double-blind, placebo-controlled trials.
Setting:
DOMINO study: United Kingdom; Memantine Clinical Trial Program: Multinational.
Participants:
DOMINO study: 295 participants enrolled during the period of February 2008 to March 2010; Memantine Clinical Trial Program: 1417 participants enrolled between August 1998 and January 2008.
Measurements:
In the DOMINO study, the co-primary outcome measures were scores on the Standardized Mini-Mental State Examination and the Bristol Activities of Daily Living Scale; Neuropsychiatric Inventory was a secondary measure. In the Memantine Clinical Trial Program, outcome measures included the Severe Impairment Battery, the 19-item Alzheimer's Disease Cooperative Study - Activities of Daily Living scale, Neuropsychiatric Inventory, and a 4-Domain Composite Index (Z-score; a post hoc assessment).
Results:
Both the pooled analysis of the Memantine Clinical Trial Program and the re-assessment of the DOMINO study with common statistical tools showed that adding memantine to donepezil therapy is associated with benefits across multiple clinical domains.
Conclusions:
The current analyses suggest that the results of the DOMINO study do not contradict previous studies which investigated the combined effects of memantine-cholinesterase inhibitor treatment.
Insights
Adding memantine to donepezil therapy offers benefits for moderate to severe Alzheimer's disease patients. This analysis confirms previous findings, supporting combination therapy for improved clinical outcomes.
Area of Science:
- Neuroscience
- Pharmacology
- Geriatrics
Background:
- Previous trials indicated memantine-cholinesterase inhibitor combination therapy is superior for moderate to severe Alzheimer's disease (AD).
- A recent study reported no additional benefit of add-on memantine compared to donepezil alone.
- This discrepancy necessitates re-evaluation of existing data.
Purpose of the Study:
- To re-evaluate the DOMINO study results using standard statistical tools.
- To apply DOMINO study statistical models to pooled data from memantine trials.
- To explore the robustness of the DOMINO study's primary findings in moderate to severe AD patients.
Main Methods:
- Post hoc analysis of the DOMINO study (N=295).
- Pooled analysis of four randomized trials (N=1417) of memantine in moderate to severe AD.
- Utilized common statistical tools and models from the DOMINO study.
Main Results:
- Re-assessment of the DOMINO study showed benefits of add-on memantine to donepezil.
- Pooled analysis of memantine trials also indicated benefits across multiple clinical domains.
- Both analyses support the efficacy of combination therapy.
Conclusions:
- The DOMINO study results do not contradict previous findings on memantine-cholinesterase inhibitor combination therapy.
- Combination therapy with memantine and donepezil demonstrates benefits in patients with moderate to severe AD.
- The findings support the continued use of memantine in combination with cholinesterase inhibitors for AD management.
More Related Videos
08:27Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by Intracerebroventricular Injection of Composited Amyloid Beta Protein
Published on: July 29, 2018
05:54Author Spotlight: Exploring Acupuncture in Alzheimer's Research from Thread-Embedding Techniques to Clinical Trials
Published on: May 10, 2024
Related Concept Videos
01:22Alzheimer's Disease: Treatment
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
01:30Combined Effects of Drugs: Antagonism
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
01:14Agonism and Antagonism: Quantification
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
01:27Combined Effects of Drugs: Synergism
Such synergistic combinations...
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...