In a double-blind RCT of patients with moderate to severe AD (MMSE scores of 5 to 14), already receiving donepezil, 404 participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n=203) or placebo (n=201) for 24 weeks.
The change in total mean scores favored memantine vs placebo treatment for SIB (Severe Impairment Battery; score range 0–100), 0.9 vs -2.5, respectively (p<0.001); for ADCS-ADL19 (19-item AD Cooperative Study-Activities of Daily Living Inventory, score range 0–54), -2.0 vs -3.4, respectively (p=0.03); and for the CIBIC-Plus (Clinician's Interview-Based Impression Change Plus Caregiver Input; score range 1–7), 4.41 vs 4.66, respectively (p=0.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.
Comment: The quality of evidence is downgraded by imprecise results (limited study size for the comparison).