Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer's Disease: A Systematic Review and Meta-Analysis

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease. Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Results: Seven studies (total n = 2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference = -0.13), activity of daily living scores (standardized mean difference = -0.10), and global assessment scores (standardized mean difference = -0.15). In addition, cognitive function scores (standardized mean difference = -0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated.