Memantine for
dementia.
Areosa SA, Sherriff F.
c/ Mauricio Legendre 17, 5-A,
Madrid, Spain, 28046.
almudenaareosa@hotmail.com
Cochrane Database Syst Rev 2003;(1):CD003154
Abstract
BACKGROUND: Alzheimer's disease, vascular and
mixed dementia are the commonest forms of dementia in older people.
There is evidence that the excitatory activity of L-glutamate plays a
role in the pathogenesis of Alzheimer's disease and in the damage from
an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate
(NMDA) type receptors, such as memantine, may prevent excitatory amino
acid neurotoxicity without interfering with the physiological actions of
glutamate required for memory and learning.
OBJECTIVES: To determine the clinical efficacy and safety of memantine
for people with Alzheimer's disease, vascular, or mixed dementia.
SEARCH STRATEGY: Trials were identified from a search of the Trial-based
Specialized Register of the Cochrane Dementia and Cognitive Improvement
Group on 9 October 2002 using the terms: memantin*, D-145, DMAA,
DRG-0267. All major health care databases and trial databases within the
scope of the group are searched regularly to keep this Register up to
date.
SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled,
randomized and unconfounded trials in which memantine was administered
to people with dementia.
DATA COLLECTION AND ANALYSIS: Data were extracted, pooled where
possible, and weighted mean differences, standardized mean differences
or odds ratios were estimated. Intention-to-treat (ITT) and observed
cases (OC) analyses are reported, where data were available.
MAIN RESULTS: There were a total of seven trials that met inclusion
criteria, of which five had sufficient data for analysis. The analysis
of change from baseline for cognition gave statistically significant
results in favour of memantine (20 mg/day) (MD: -2,83 95% CI -4.37 to
-1.29, P=0.0003) at 28 weeks and for memantine (30mg/day) at 6 weeks
(MD: -3.04. 95% CI -5.68 to -0.40, P=0.02). Effects on Activities of
Daily living (ADL) were difficult to interpret. One study provided data
using a non-validated scale for measuring five simple instrumental tasks
under the guidance of an investigator. When pooled with another study
the analysis gave statistically significant results in favour of
memantine for 30 mg/day at 6 weeks (SMD: -1.36 95% CI -1.77 to -0.96,
P=0.0003). Mood and behaviour: One trial provided data on memantine 30
mg/day at 6 weeks using the NOSIE scale. The OC analysis found
statistically significant differences in favour of treatment (MD: 23.30
95% CI 17.83 to 28.77, P<0.00001). Global scales: The analysis
revealed a statistically significant difference in favour of memantine
(20mg/day ) at 6 weeks (MD: -12.30 95% CI -16.90 to -7.70,
P<0.00001). Similar results were found for larger doses (memantine 30
mg/day) at 6 weeks in a pooled meta-analysis of two other studies (WMD:
-10.77 95% CI -13.46 to -8.09, P<0.00001). With regard to the Global
Impression of Change three studies found statistically significant
results in favour of 10, 20 and 30 mg/day of memantine compared with
placebo at 6 or 12 weeks. There was a benefit in favour of memantine (20
mg/day) compared with placebo at 6 weeks, for the numbers improved (
24/41 compared with 11/41)(OR, 3.85, 95% CI 1.52 to 9.75, P=0.004), in
favour of memantine (30 mg/day) compared with placebo at 6 weeks, for
the numbers improved ( 20/30 compared with 8/29)(OR, 5.25, 95% CI 1.72
to 15.98, P=0.004) and in favour of memantine (10 mg/day) compared with
placebo at 12 weeks, for the numbers improved ( 60/82 compared with
38/84)(OR, 3.30, 95% CI 1.72 to 6.33, P=0.0003). In general memantine
seemed to be well tolerated. There was no statistically significant
difference between memantine and placebo for the three studies that
reported adverse events.There were some data on specific adverse events.
In one study the incidence of restlessness by the end of the treatment
at 6 weeks was statistically significantly lower in the placebo group
than in the group taking memantine 30 mg/day (15/30 compared with 2/29)
(OR 13.50, 95% CI 2.71 to 67.19, P=0.001). The number of dropouts was
similar in treatment and placebo groups at 6 or 28 weeks time for
memantine 20 mg/day and at 6 weeks for memantine 30 mg/day.
REVIEWER'S CONCLUSIONS: Memantine is a safe drug and may be useful for
treating Alzheimer's, vascular,and mixed dementia of all severities.
Most of the trials so far reported have been small and not long enough
to detect clinically important benefits. However there is a possible
benefit on cognition and global measures, and an early improvement in
behaviour in people with dementia. More studies are needed.
