Abstract
Objective: To evaluate the effect of memantine added to cholinesterase inhibitors (ChEIs) on agitation by analyzing score shifts on the agitation subscale of the Neuropsychiatric Inventory (NPI) in patients with Alzheimer’s disease (AD).
Background: Agitation is a common neuropsychiatric symptom associated with AD. Previous studies suggest that memantine added to ChEIs provides benefits for neuropsychiatric symptoms in moderate-to-severe AD patients.
Design/Methods: Data were pooled from three phase 3, randomized, double-blind, placebo-controlled trials (RCT); two in moderate-to-severe AD and one in mild-to-moderate AD; all receiving ChEIs. Shifts from baseline in NPI-agitation subscale scores were evaluated post hoc at weeks 12 and 24 using baseline score cutoffs of 0, >0, <4 and ≥4. Score shift distributions for memantine/ChEI vs placebo/ChEI were analyzed by Chi-Square test.
Results: 1140 patients were included (576 memantine/ChEI, 564 placebo/ChEI), with mean age 75.72 (SD=8.194), mean MMSE 11.05 (SD=3.007); and mean NPI-agitation score 1.29 (SD=2.208). At week 24, in patients without baseline agitation (NPI-agitation score=0; n=656), 88.8% memantine/ChEI vs 81.0% placebo/ChEI remained without agitation; 11.2% vs 19.0% developed agitation (P=0.0058). In patients with agitation at baseline (NPI-agitation score >0; n=381), the percentage who experienced improvement (NPI-agitation score=0) numerically favored memantine/ChEI over placebo/ChEI (43.6% vs 35.6%, P=0.1102). When baseline NPI-agitation score <4 was evaluated (n=883), 94.4% memantine/ChEI vs 88.7% placebo/ChEI patients remained at score <4, while 5.6% and 11.3% had increased agitation to score ≥4 (P=0.0022) at week 24. For baseline NPI-agitation score ≥4 (n=154), 70.2% memantine/ChEI and 54.3% placebo/ChEI patients had decreased agitation to score <4, while 29.8% and 45.7% remained at score ≥4 (P=0.0412) at week 24. Similar results were observed at week 12.
Conclusions: In this large AD RCT pooled analysis, the combination of memantine and ChEIs significantly decreased the emergence of agitation, reduced agitation severity, and stabilized agitation symptoms over 12 and 24 weeks compared with ChEIs alone.
Study Supported by:
Allergan plc
Disclosure: Dr. Atri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Atri has received honoraria for consulting, educational lectures/programs/materials or advisory boards from Allergan, Alzheimer’s Association, Axovant, Biogen, Grifols, Harvard Medical School Graduate Continuing Education, Lundbeck, Merck, Oxford Univ. Dr. Atri has received research support from Dr. Atri’s institution has contracts or received investigational clinical trial related funding from The American College of Radiology, Avid, Biogen, Lilly, Lundbeck, Merck, and vTV. Dr. Agronin has nothing to disclose. Dr. Grossberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Grossberg has served as a consultant for Acadia, Allergan, Avanir, Axovant, GE, Genentech, Lundbeck, Novartis, Otsuka, Roche, and Takeda, and for the Speaker’s Bureau for Acadia. Dr. Grossberg has received research support from Dr. Grossberg has received research support and funds from Cognoptix, Janssen, and NIH. Dr. Hendrix has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pentara Corporation employee. Dr. Ellison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pentara Corporation employee. Dr. Edwards has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan employee. Dr. Kerolous has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan employee.
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.