Long-term Efficacy and Safety of Donepezil Dose Escalation for Patients with Alzheimer?s Disease in a Clinical Setting

Background: Donepezil is a routinely prescribed cognitive enhancer for patients with Alzheimer’s disease (AD), however the effectiveness and safety of long-term high doses remains largely unexplored. Objective: We investigated the long-term efficacy and safety of Donepezil dose escalation in reducing global cognitive decline for patients with AD in a clinical setting. Method: In a naturalistic, open-label, controlled study design, 71 mild to moderate AD patients from a tertiary clinic were prescribed Donepezil 5mg/day for 12 months (phase 1), while 9 AD patients received no treatment. Patients who showed limited benefits (N=30) with Donepezil 5mg/day were titrated up to 10mg/day for a subsequent 12 months (phase 2) and the remaining (N=41) patients continued on 5mg/day. The primary outcome was global cognition, indexed using the Mini-Mental State Examination (MMSE). Results: Phase 1 trends confirmed Donepezil 5mg/day was better than no treatment at reducing cognitive decline (p = .09, f=.18). Phase 2 trends indicated that for patients who showed limited response to Donepezil 5mg/day, Donepezil 10mg/day was more effective in reducing slope of cognitive decline (p = 0.13, f= .42). Additionally, the patients that were titrated up to 10mg/day had comparable treatment benefits to those patients that remained on 5mg/day during phase 2 (p = .32, f =.12). Side effects in the 10mg/day group were not significantly different from the side effects in the 5mg group (t (67)=-1.27, p=.21). Conclusion: Donepezil dose escalation in patients with AD is safe and may result in large noticeable effects on cognition, with effects comparable to patients who initially responded well to 5mg/day.