Memantine for dementia.

BACKGROUND: Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting 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, or vascular or mixed dementia.

SEARCH STRATEGY: Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 15 April 2003 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: Effect of memantine in patients with moderate to severe Alzheimer's disease: analysis of the change from baseline at 28 weeks gave statistically significant results in favour of memantine for 20 mg/day on cognition (MD: 6.1. 95% CI 2.99 to 9.21, P=0.0001) activities of daily living (MD 2.10, 95% CI 0.46 to 3.74, p=0.01) and in the global clinical impression of change measured by the CIBIC-Plus at 28 weeks (MD -0.30, 95% CI -0.58 to -0.02, p=0.04), in all cases the analysis was the ITT-LOCF population (Reisberg 2000). There were no significant differences between memantine and placebo for the number of drop-outs and total number of adverse effects, but a significant difference in favour of memantine for the number who suffer agitation. Effect of memantine in patients with mild to moderate vascular dementia: analysis of the change from baseline at 28 weeks gave statistically significant results in favour of memantine ( 20 mg/day ) for cognition (MD -2.19, 95% CI -3.16 to -1.21, P<0.0001) but there was no benefit for the clinical impression of change, or for global measures of dementia (MMM300, and MMM500). There were no significant differences between memantine and placebo for the number of drop-outs and total number of adverse effects, but a significant difference in favour of memantine for the number who suffer agitation. Effect of memantine in patients with Alzheimer's disease and vascular dementia at 12 weeks: there was no statistically significant difference between memantine (10 mg/day) and placebo in activities of daily living. There was a benefit in favour of memantine (10 mg/day) compared with placebo at 12 weeks, for the numbers improved in terms of clinical impression of change (60/82 compared with 38/84 - OR 3.30, 95% CI 1.72 to 6.33, P=0.0003) (Winblad 1999). Effect of memantine in patients with vascular dementia, Alzheimer's disease and dementia of non-specified type at 6 weeks: there were beneficial effects on cognition (Ditzler 1991), activities of daily living (Ditzler 1991, Pantev 1993), behaviour (Pantev 1993) and global scales (Gortelmeyer 1992; Pantev 1993; Ditzler 1991) and in global impression of change (Gortelmeyer 1992; Ditzler 1991). There were no significant differences between memantine and placebo for the number of drop-outs and total number of adverse effects, but a significant difference in favour of placebo for the number who suffer restlessness.

REVIEWER'S CONCLUSIONS: There is a beneficial effect of memantine (20 mg/day) for patients with moderate to severe Alzheimer disease on cognition and functional decline but not in the clinical impression of change. Patifor patients with moderate to severe Alzheimer disease on cognition and functional decline but not in the clinical impression of change. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but again this effect was not clinically discernible. There is a possible beneficial effect on cognition, function and global scales for memantine at 6 weeks in mixed populations. The drug is well tolerated and the incidence of adverse effects is low. More studies are needed.