TITLE: Memantine in Combination with Cholinesterase Inhibitors for Alzheimer s Disease: Clinical Effectiveness DATE: 30 October 2008 RESEARCH QUESTION: What is the evidence for using memantine in combination with a cholinesterase inhibitor for the treatment of Alzheimer s disease? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, the Cochrane Library (Issue 4, 2008), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international health technology agencies, and a focused Internet search. Results include articles published between 2003 and October 2008, and are limited to English language publications only. No filters were applied to limit the retrieval by study type. Internet links are provided, where available. RESULTS: HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports, systematic reviews, and meta-analyses are presented first. These are followed by randomized controlled trials, controlled clinical trials, and observational studies. One health technology assessment, four systematic reviews, four randomized controlled trials, one controlled clinical trial, and three observational studies were identified from the literature search results. Additional articles of interest are listed in the Appendix. Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by email or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information on available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.
Health technology assessments 1. Loveman E, Green C, Kirby J, Takeda A, Picot J, Payne E, et al. The clinical and costeffectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease. Health Technol Assess 2006;10(1):iii-iv, ix-xi, 1-160. PubMed: PM16409879 Available: http://www.hta.ac.uk/project/1398.asp. Systematic reviews and meta-analyses 2. Kirby J, Green C, Loveman E, Clegg A, Picot J, Takeda A, et al. A systematic review of the clinical and cost-effectiveness of memantine in patients with moderately severe to severe Alzheimer's disease. Drugs Aging 2006;23(3):227-40. PubMed: PM16608378 3. Forchetti CM. Treating patients with moderate to severe Alzheimer's disease: implications of recent pharmacologic studies. Prim Care Companion J Clin Psychiatry 2005;7(4):155-61. PubMed: PM16163398 4. Rossom R, Adityanjee, Dysken M. Efficacy and tolerability of memantine in the treatment of dementia. Am J Geriatr Pharmacother 2004;2(4):303-12. PubMed: PM15903287 5. Standridge JB. Pharmacotherapeutic approaches to the treatment of Alzheimer's disease. Clin Ther 2004;26(5):615-30. PubMed: PM15220008 Randomized controlled trials 6. Porsteinsson AP, Grossberg GT, Mintzer J, Olin JT. Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res 2008;5(1):83-9. PubMed: PM18288936 7. Feldman HH, Schmitt FA, Olin JT. Activities of daily living in moderate-to-severe Alzheimer disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatment. Alzheimer Dis Assoc Disord 2006;20(4):263-8. PubMed: PM17132971 8. Schmitt FA, van Dyck CH, Wichems CH, Olin JT. Cognitive response to memantine in moderate to severe Alzheimer disease patients already receiving donepezil: an exploratory reanalysis. Alzheimer Dis Assoc Disord 2006;20(4):255-62. PubMed: PM17132970 9. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291(3):317-24. PubMed: PM14734594 Controlled clinical trials 10. Cummings JL, Schneider E, Tariot PN, Graham SM. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006;67(1):57-63. PubMed: PM16832078 2
Observational studies 11. Riepe MW, Adler G, Ibach B, Weinkauf B, Tracik F, Gunay I. Domain-specific improvement of cognition on memantine in patients with Alzheimer's disease treated with rivastigmine. Dement Geriatr Cogn Disord 2007;23(5):301-6. PubMed: PM17356273 12. Dantoine T, Auriacombe S, Sarazin M, Becker H, Pere JJ, Bourdeix I. Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer's disease who failed to benefit from previous cholinesterase inhibitor treatment. Int J Clin Pract 2006;60(1):110-8. PubMed: PM16409439 13. Riepe MW, Adler G, Ibach B, Weinkauf B, Gunay I, Tracik F. Adding memantine to rivastigmine therapy in patients with mild-to-moderate Alzheimer's disease: results of a 12-week, open-label pilot study. Prim Care Companion J Clin Psychiatry 2006;8(5):258-63. PubMed: PM17235381 PREPARED BY: Keiko Asakawa, MA, MBA, PhD, Health Economist Carolyn Spry, MLIS, Information Specialist Health Technology Inquiry Service Email: htis@cadth.ca Tel: 1-866-898-8439 3
APPENDIX FURTHER INFORMATION: Review articles 14. Farlow MR, Miller ML, Pejovic V. Treatment options in Alzheimer's disease: maximizing benefit, managing expectations. Dement Geriatr Cogn Disord 2008;25(5):408-22. PubMed: PM18391487 15. Hsiung GY, Feldman HH. Pharmacological treatment in moderate-to-severe Alzheimer's disease. Expert Opin Pharmacother 2008;9(15):2575-82. PubMed: PM18803446 16. Beier MT. Treatment strategies for the behavioral symptoms of Alzheimer's disease: focus on early pharmacologic intervention. Pharmacotherapy 2007;27(3):399-411. PubMed: PM17316151 17. Schmitt F, Ryan M, Cooper G. A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer's disease. Expert Opin Drug Metab Toxicol 2007;3(1):135-41. PubMed: PM17269900 18. Bullock R. Efficacy and safety of memantine in moderate-to-severe Alzheimer disease: the evidence to date. Alzheimer Dis Assoc Disord 2006;20(1):23-9. PubMed: PM16493232 19. Robinson DM, Keating GM. Memantine: a review of its use in Alzheimer's disease. Drugs 2006;66(11):1515-34. PubMed: PM16906789 20. Doody RS. Refining treatment guidelines in Alzheimer's disease. Geriatrics 2005;Suppl:14-20. PubMed: PM16025771 21. Grossberg GT. Rationalizing therapeutic approaches in Alzheimer's disease. CNS Spectr 2005;10(11 Suppl 18):17-21. PubMed: PM16273026 22. Xiong G, Doraiswamy PM. Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not? Geriatrics 2005;60(6):22-6. PubMed: PM15948662 23. Schmitt B, Bernhardt T, Moeller HJ, Heuser I, Frolich L. Combination therapy in Alzheimer's disease: a review of current evidence. CNS Drugs 2004;18(13):827-44. PubMed: PM15521788 Additional references 24. Press D, Alexander M. Treatment of dementia. In: UpToDate [database online]. Version 16.2. Waltham (MA): UpToDate; 2008. Article available for purchase at http://www.uptodate.com See section: Memantine plus cholinesterase inhibitors 25. Shua-Haim J, Smith J, Picard F, Sedek G, Athalye S, Pommier F, et al. Steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease not affected by co-administration of memantine: an open-label, crossover, single-centre study. Clin Drug Investig 2008;28(6):361-74. PubMed: PM18479178 4
26. Herrmann N. Treatment of moderate to severe Alzheimer's disease: rationale and trial design. Can J Neurol Sci 2007;34 Suppl 1:S103-S108. PubMed: PM17469692 27. Grossberg GT, Edwards KR, Zhao Q. Rationale for combination therapy with galantamine and memantine in Alzheimer's disease. J Clin Pharmacol 2006;46(7 Suppl 1):17S-26S. PubMed: PM16809811 28. van Dyck CH. Understanding the latest advances in pharmacologic interventions for Alzheimer's disease. CNS Spectr 2004;9(7 Suppl 5):24-8. PubMed: PM15241297 29. Voisin T, Reynish E, Portet F, Feldman H, Vellas B. What are the treatment options for patients with severe Alzheimer's disease? CNS Drugs 2004;18(9):575-83. PubMed: PM15222774 5