POST HOC EVIDENCE FOR AN ADDITIVE EFFECT OF MEMANTINE AND DONEPEZIL: CONSISTENT FINDINGS FROM DOMINO-AD STUDY AND MEMANTINE CLINICAL TRIAL PROGRAM
S. Hendrix, N. Ellison, S. Stanworth, V. Otcheretko, P.N. Tariot
J Prev Alz Dis 2015;2(3):165-171
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.
S. Hendrix ; N. Ellison ; S. Stanworth ; V. Otcheretko ; P.N. Tariot (2015): Post Hoc Evidence for an Additive Effect of Memantine and Donepezil: Consistent Findings from DOMINO-AD Study and Memantine Clinical Trial Program. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.66