Memantine for dementia

Memantine has a beneficial effect on cognitive function and functional decline measured at 6 months in patients with moderate to severe Alzheimer's disease or vascular dementia.

A Cochrane review included 15 studies with a total of 3 731 subjects.

• Moderate to severe AD, 20 mg/day, 24 to 28 weeks. Pooled data (3 studies, n=1 006) indicated a small beneficial effect at six months on cognition (2.97 points on the 100 point Severe Impairment Battery [SIB], 95% CI 1.68 to 4.26), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09) and behaviour (2.76 points on the 144 point Neuropsychiatric Inventory [NPI], 95% CI 0.88 to 4.63), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41).
• Mild to moderate AD, 20 mg/day, 24 weeks. Pooled data from three unpublished studies (n=1 305) indicated a marginal benefical effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25) but no effect on behaviour, activities of daily living or OC analysis of cognition.
• Mild to moderate vascular dementia, 20 mg/day, 28 weeks. Pooled data from two six month studies (n=900) indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83), and behaviour (0.84 95% CI 0.06 to 0.91) but this was not supported by clinical global measures.
• Severe vascular dementia, Alzheimer's disease or mixed dementia, 10 mg/day, 12 weeks. One study (n=167) showed a large benefit in favour of memantine compared with placebo in global impression (CGI 60/82 [73%] vs. 38/84 [45%]: OR 3.30, 95% CI 1.72 to 6.33). BGP care dependence subscore indicated a significant difference in favour of memantine in function.
• Pooled analysis (8 trials): memantine in mild to severe Alzheimer's disease and vascular dementia at 24 to 28 weeks. There was a significant benefit of memantine on global impression apparent on 7-point clinical global measures of change (WMD 0.15, 95% CI 0.07 to 0.23), on cognitive function (SMD 0.24, 95% CI 0.17 to 0.30), on patients' ability to perform activities of daily living (SMD 0.08, 95% CI 0.01 to 0.15), and on patient's mood and behaviour as assessed by the NPI or the 'disturbed behaviour' subscale of the NOSGER (SMD 0.11, 95% CI 0.04 to 0.19).

Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). Memantine was well tolerated.

A systematic review including 5 RCTs with a total of 1 944 subjects was abstracted in DARE. Significant improvement on the ADAS-cog was found for patients with mild to moderate vascular dementia (VD) receiving memantine (WMD –2.20, 95% CI –3.24 to –1.15; 2 RCTs) as compared to placebo. A significant difference in favour of memantine was found on the NOSGER-mood (VD, all severity levels) and the NPI (Alzheimer's disease, all severity levels).

Ədəbiyyat

1. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev 2006;(2):CD003154.
2. Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 2008 Mar 4;148(5):379-97.