High-dose donepezil or memantine: Next step for Alzheimer’s disease?
Larger dosages may benefit patients who have ‘maxed out’ existing therapies
Recommendations
Because there are few FDA-approved treatments for AD, higher doses of donepezil or memantine may be an option for patients who have “maxed out” on their AD therapy or no longer respond to lower doses. Higher doses of donepezil (23 mg/d) and memantine (28 mg/d) could improve medication adherence because both are once-daily preparations. In clinical trials, donepezil, 23 mg/d, was more effective than donepezil, 10 mg/d.9 Whether memantine ER, 28 mg/d, is superior to memantine IR, 20 mg/d, needs to be investigated in head-to-head, double-blind, controlled studies.
For patients with moderate to severe AD, donepezil, 23 mg, is associated with greater benefits in cognition compared with donepezil, 10 mg/d.9 Similarly, because of potentially superior efficacy because of a higher dose, memantine ER, 28 mg, might best help patients with moderate to severe AD, specifically those who either don’t respond or lose response to memantine IR, 20 mg/d. Combining a ChEI, such as donepezil, with memantine is associated with slower cognitive decline and short and long-term benefits on measures of cognition, activities of daily living, global outcome, and behavior.7,26 However, additional clinical trials are needed to assess the safety, tolerability, and efficacy of combination therapy with higher doses of donepezil and memantine ER.
Related Resources
- Alzheimer’s Disease Education and Referral Center. www.nia.nih.gov/Alzheimers.
- Lleó A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med. 2006;57:513-533.
Drug Brand Names
- Donepezil • Aricept
- Galantamine • Razadyne
- Memantine • Namenda
- Rivastigmine • Exelon
- Tacrine • Cognex
Disclosures
Dr. Grossberg’s academic department has received research funding from Forest Pharmaceuticals and Pfizer Inc. Dr. Grossberg has received grant/research support from Baxter BioScience, Forest Pharmaceuticals, Janssen, the National Institutes of Health, Novartis, and Pfizer, Inc.; is a consultant to Baxter BioScience, Forest Pharmaceuticals, Merck, Novartis, and Otsuka; and is on the Safety Monitoring Committee for Merck.
Dr. Singh reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
