Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis

• Published in: International journal of geriatric psychiatry Vol. 23; no. 5; pp. 537 - 545
• Main Authors: Gauthier, S., Loft, H., Cummings, J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-05-2008; Wiley; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; agitation; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; Alzheimer's disease; Antiparkinson Agents - therapeutic use; Behavioral Symptoms - drug therapy; behaviour; Biological and medical sciences; Clinical trials; Data analysis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Excitatory Amino Acid Antagonists - therapeutic use; Female; Fundamental and applied biological sciences. Psychology; Geriatric psychiatry; Geriatrics; Humans; Male; Medical sciences; Medical treatment; memantine; Memantine - therapeutic use; Neurology; Neuropsychiatric Inventory; Neuropsychological Tests; pooled data; Psychoanalysis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychotropic drugs; Randomized Controlled Trials as Topic; Treatment Outcome; Agitation; Questionnaire; Neuropsychiatric Inventory; Alzheimer disease; Glutamate receptor; Metaanalysis; Amantadine derivatives; Improvement; pooled data; Degenerative disease; Pool; Antagonist; Behavior; Alzheimer's disease; Human; Nervous system diseases; Patient; Psychometrics; Antialzheimer agent; Antiparkinson agent; Cerebral disorder; Symptomatology; Gerontology; Memantine; Central nervous system disease; Mental disorder; behaviour; NMDA receptor; Severe; Elderly; Inventory; Geriatrics
• ISSN: 0885-6230; 1099-1166
• DOI: 10.1002/gps.1949

Introduction
Behavioural disturbances are a common and distressing aspect of Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of memantine on behavioural disturbances in patients with moderate to severe AD.
Methods
Data were pooled from six 24/28‐week, randomised, placebo‐controlled, double‐blind studies. Of the 2,311 patients included in these studies, 1,826 patients with moderate to severe AD (MMSE <20) were included in this analysis, corresponding to the extended indication for memantine in Europe. In this subgroup, 959 patients received memantine 20 mg/day and 867 received placebo. Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total and single‐item scores at weeks 12 and 24/28.
Results
At weeks 12 and 24/28, ITT analysis demonstrated that memantine treatment produced statistically significant benefits over placebo treatment in NPI total score (p = 0.001 and p = 0.008), and in NPI single items: delusions (p = 0.007 week 12, p = 0.001 week 24/28), hallucinations (p = 0.037 week 12), agitation/aggression (p = 0.001 week 12, p = 0.001 week 24/28), and irritability/lability (p = 0.005 week 24/28), LOCF population. Analysis of the patients without symptoms at baseline indicated reduced emergence of agitation/aggression (p = 0.002), delusions (p = 0.047), and disinhibition (p = 0.011), at week 12, and of agitation/aggression (p = 0.002), irritability/lability (p = 0.004), and night‐time behaviour (p = 0.050) at week 24/28 in those receiving memantine. OC analyses yielded similar results.
Conclusions
The data suggest that memantine is effective in treating and preventing the behavioural symptoms of moderate to severe AD. Specific persistent benefits were observed on the symptoms of delusions and agitation/aggression, which are known to be associated with rapid disease progression, increased caregiver burden, early institutionalisation, and increased costs of care. Copyright © 2007 John Wiley & Sons, Ltd.