Strategies for managing patients with moderate to severe Alzheimer’s disease: high‐dose donepezil vs. memantine combination

Abstract

AbstractBackgroundsWhen dementia patients who took already a maintenance dose of 10mg donepezil get worse to advanced stage, clinicians would consider and select which one is better between higher‐dose donepezil (23 mg/day) and memantine combination.ObjectivesTo compare the clinical benefits between high‐dose donepezil and memantine (20 mg/day) combination in moderate to severe Alzheimer’s diseaseMethodsA single center, retrospective, observational study was conducted. Patients with moderate to severe AD who were treated with a stable dose of donepezil were included. They started further treatments such as higher‐dose donepezil or memantine combination because they showed poor or waning response to a maintenance dose. After 6 months follow‐up, clinical efficacy and safety were compared between two groups, higher‐dose donepezil and memantine combination.ResultsA total of 108 patients, 35 with higher‐dose donepezil and 75 with memantine combination, were included. Baseline characteristics such as age, sex, education, MMSE, and CDR were similar between groups. After follow‐up, changes of MMSE and CDR were not different. Treatment responses measured as CGI‐C were as follows: 41.3% (improved 31, not changed 25, and worse 9) of patients improved after memantine combination and 22.9% (improved 8, not changed 12, and worse 15) improved after higher‐dose donepezil (p = 0.069). Adverse events were not different. Among patients with memantine combination, those who had no benefits to the initial donepezil showed better responses (27 vs. 48). Patients who had benefits to lower dose of donepezil showed better responses (24 vs. 11) after higher‐dose.ConclusionBoth of higher‐dose donepezil and memantine combination, which are approved as effective in moderate to severe AD, were not different in clinical benefits and safety. Although not statistically significant, treatment responses showed some differences. Patients who had shown good response at the time of the initial therapy of donepezil preferred higher‐dose donepezil over memantine combination, whereas those who did not respond to the initial donepezil had more effective after memantine was added. Further studies including randomized blind trials could strengthen these findings.