Adding Memantine to Cholinesterase Inhibitor Regimen Improves Alzheimer Disease Neuropsychiatric Syndromes

Jeffrey L. Cummings, MD, ScD

In patients with moderate to severe Alzheimer disease, a treatment regimen combining memantine with a cholinesterase inhibitor (ChEI) may provide significant benefits for psychosis and neurovegetative behavioral syndromes compared with a ChEI alone, according to data from a post hoc analysis.

The data, pulled from 3 randomized, double-blind, placebo controlled 24-week trials, were presented at the 2019 American Academy of Neurology Annual Meeting, May 4-10, in Philadelphia.

“Neuropsychiatric symptoms negatively impact daily function and quality of life, hasten time to institutionalization, and increase overall healthcare costs,” according to the authors, led by Jeffrey L. Cummings, MD, ScD, director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health. As previous studies have shown a significant benefit for memantine on several domain scores of the Neuropsychiatric Inventory (NPI) compared with placebo, the investigators sought to assess the effect of memantine in addition to a ChEI compared with a ChEI alone in patients with Alzheimer disease.

Data was pooled from 3 trials — Tariot et al, JAMA 2004; Porsteinsson et al, Alzheimer Research 2008; and Grossberg et al, CNS Drugs 2013 — totaling 1262 patients. For this analysis, the 12 items of the NPI were grouped into 4 domains: psychosis, accounting for agitation/aggression, hallucinations, delusions, and irritability/lability; neurovegetative, accounting for aberrant motor behavior, nighttime behavior, and appetite/eating change; frontal, accounting for disinhibition and euphoria/elation; and mood, accounting for anxiety, depression/dysphoria, and apathy.

Among the total cohort, 637 patients were treated with concomitant memantine and ChEIs, while 625 received placebo and ChEIs. Mean age was 75.7±8.3 years; baseline Mini Mental State Exam score was 11.5±3.5, and baseline NPI total score was 14.9±14.6.

Across all 4 syndrome domains, favorable treatment outcomes were more apparent in the group receiving concomitant memantine and ChEIs compared with those who received placebo and ChEIs.

Statistically significant improvements in both psychosis symptoms and neurovegetative scores were recorded for patients who received concomitant memantine and ChEIs at both 12 weeks and 24 weeks (psychosis 12 weeks: LSMD &#8209;1.167, P <.0001; 24 weeks: LSMD -1.238, P <.0001; neurovegetative 12 weeks: LSMD -0.621, P =.0103; 24 weeks: LSMD -0.583, P =.0441).

No significant differences in scores for the frontal or mood domains at 12 or 24 weeks were observed.

All told, no analyses showed the placebo and ChEI treatment group superior to memantine and ChEI across any of the domains.

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REFERENCE

Cummings JL, Grossberg GT, Porsteinsson AP, Hendrix S, Ellison N, Kerolous M. The effects of memantine added to cholinesterase inhibitors on NPI behavioral domains: pooled post hoc analysis of 3 randomized controlled trials in patients with moderate to severe AD. Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA.