Tolerability of switching from donepezil to memantine treatment in patients with moderate to severe Alzheimer's disease

Memantine has shown cognitive, functional, and behavioural benefits in Alzheimer's disease (AD) studies. An 8-week, randomised, double-blind study in patients with moderate to severe AD (DSM-IV -TR criteria and an MMSE ≤ 18) assessed the tolerability of switching AD patients, in whom there was doubt about the continued efficacy of donepezil (10 mg OD), to memantine (10 mg BID). Patients (N=46, MMSE range 6-18, mean=13) were initiated on memantine treatment according to the labelling and simultaneously randomised to either abrupt or stepwise (5mg for 2 weeks) discontinuation of donepezil. Tolerability, measured by adverse events (AEs), was the primary endpoint and efficacy measured by the Clinician's Global Impression of Change (CGI-C) was the secondary endpoint. The number of withdrawals was low, in total 4/47 patients withdrew (1 withdrew consent before memantine treatment, 1 due to lack of efficacy, and 2 due to AEs). Eighteen patients (39%) reported one or more AE(s), with accidental injury (4 patients), vertigo (2 patients) and anxiety (2 patients) reported in more than one patient. There were no clinically important differences in AEs between the two switch schedules. The CGI-C scores either stabilised or improved in 32/43 (74%) of patients switched from donepezil to memantine. No difference between the two switch schedules was observed. In conclusion, the tolerability when switching AD patients from donepezil to memantine was good. After being switched to memantine, the majority of the patients remained stable or improved clinically. Several acetylcholinesterase inhibitors (AChEIs) are approved for the treatment of mild to moderate AD, based on the symptomatic improvements of cognitive function and global clinical state. AChEIs and memantine have different mechanisms of action, as well as different adverse event profiles. In patients on AChEI-treatment, progress in the disease and efficacy of treatment should be evaluated. Switching treatment should be considered when patients start to decline more rapidly or when they can no longer tolerate their treatment. Therefore, it is important to evaluate how AD patients respond when switched from an AChEI to memantine. The aim of this study was to evaluate tolerability, safety, and efficacy when switching AD treatment from the AChEI donepezil to memantine.