Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer's Disease: Post Hoc Analyses From a Randomized, Controlled, Clinical Trial of Patients Treated With Cholinesterase Inhibitors

George T Grossberg, Gustavo Alva, Suzanne Hendrix, Noel Ellison, Mary C Kane, John Edwards, George T Grossberg, Gustavo Alva, Suzanne Hendrix, Noel Ellison, Mary C Kane, John Edwards

Abstract

Memantine extended release (ER) significantly outperformed placebo on co-primary endpoints of Clinician's Interview-based Impression of Change Plus Caregiver Input (CIBIC-Plus) and baseline to endpoint changes on the Severe Impairment Battery (SIB) in a 24-week, randomized trial (NCT00322153) in patients with moderate to severe Alzheimer's disease taking a cholinesterase inhibitor (ChEI). A post hoc analysis compared patients receiving memantine ER/ChEI to placebo/ChEI for time to onset of response and if the response was maintained (achieving improvement at weeks 8, 12, or 18 and maintaining through endpoint/week 24) on the SIB, the Neuropsychiatric Inventory (NPI), CIBIC-Plus, and Activities of Daily Living (ADL) using Fisher exact test. A second post hoc analysis compared percentages of patients for all possible combinations of 2 to 4 assessments with either no decline or clinically notable response using Wald χ. Significantly greater percentages of memantine ER/ChEI patients achieved an early response that was maintained on SIB, NPI, and CIBIC-Plus (P<0.05) versus placebo/ChEI. Significantly greater percentages of memantine ER/ChEI-treated patients achieved and maintained a clinically notable response on ADL/NPI, SIB/ADL/NPI, and SIB/ADL/CIBIC-Plus, compared with placebo/ChEI (P<0.05). Memantine ER results in early, maintained improvement in patients with moderate to severe Alzheimer's disease concurrently taking ChEIs, compared with cholinesterase treatment alone.

Figures

FIGURE 1
FIGURE 1
SIB maintenance of response (OC). Fisher exact test. BL indicates baseline; ChEI, cholinesterase inhibitor; ER, extended release; OC, observed cases; SIB, Severe Impairment Battery. *P<0.05, **P<0.01.
FIGURE 2
FIGURE 2
NPI maintenance of response (OC). Fisher exact test. BL indicates baseline; ChEI, cholinesterase inhibitor; ER, extended release; NPI, Neuropsychiatric Inventory; OC, observed cases. *P<0.05, **P<0.01.
FIGURE 3
FIGURE 3
CIBIC-Plus maintenance of response (OC). Fisher exact test. BL indicates baseline; ChEI, cholinesterase inhibitor; CIBIC-Plus, Clinician’s Interview-based Impression of Change Plus Caregiver Input; ER, extended release; OC, observed cases. *P<0.05.
FIGURE 4
FIGURE 4
Response across multiple parameters: no decline. ADL indicates Activities of Daily Living; ChEI, cholinesterase inhibitor; CIBIC-Plus, Clinician’s Interview-based Impression of Change Plus Caregiver Input; ER, extended release; NPI, Neuropsychiatric Inventory; SIB, Severe Impairment Battery.
FIGURE 5
FIGURE 5
Response across multiple parameters: clinically notable response. Fisher exact test. ADL indicates Activities of Daily Living; ChEI, cholinesterase inhibitor; CIBIC-Plus, Clinician’s Interview-based Impression of Change Plus Caregiver Input; ER, extended release; NPI, Neuropsychiatric Inventory; SIB, Severe Impairment Battery. *P<0.05.

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Source: PubMed

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