The effects of memantine on behavioral disturbances in patients with Alzheimer’s disease: A meta-analysis

Background: Memantine is effective in the treatment of behavioral disturbances in patients with Alzheimer’s disease. It has not yet been fully determined which behavioral disturbances respond best to memantine. Methods: We conducted a meta-analysis of memantine vs control (placebo or usual care) for the treatment of individual behavioral disturbances (delusion, hallucination, agitation/aggression, dysphoria, anxiety/phobia, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity/activity disturbances, nighttime disturbance/diurnal rhythm disturbances, and eating disturbances). Randomized controlled studies of memantine in patients with Alzheimer’s disease were included in this study. To evaluate these outcomes, standardized mean difference (SMD), with 95% confidence intervals (95% CIs), based upon a random-effects model was evaluated in the meta-analysis. Results: A total of 11 studies (n=4,261; memantine vs placebo: N=4, n=1,500; memantine + cholinesterase inhibitors [M + ChEIs] vs ChEIs: N=7, n=2,761) were included in the meta-analysis. Compared to control, memantine showed significant improvement in agitation/aggression (SMD =-0.11; 95% CIs =-0.20, -0.03; P=0.01; I²=47%), delusion (SMD =-0.12; 95% CIs =-0.18, -0.06; P=0.0002; I²=0%), disinhibition (SMD =-0.08; 95% CIs =-0.15, -0.00; P=0.04; I²=0%), and nighttime disturbance/diurnal rhythm disturbances (SMD =-0.10; 95% CIs =-0.18, -0.02; P=0.02; I²=36%). Memantine was also marginally superior to control in hallucination (SMD =-0.06; 95% CIs =-0.12, 0.01; P=0.07; I²=0%) and irritability/lability (SMD =-0.09; 95% CIs =-0.19, 0.01; P=0.07; I²=42%). Memantine is similar to control in dysphoria, anxiety/ phobia, euphoria, apathy, and eating disturbance. Conclusion: The meta-analysis suggest that memantine has benefits for the treatment of most of the behavioral disturbances in patients with Alzheimer’s disease. Memantine does not deteriorate negative symptoms as behavioral disturbances in patients with Alzheimer’s disease.