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Memantine for the Treatment of Alzheimer’s Disease

Tolerability and Safety Data from Clinical Trials

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Abstract

Background: Memantine, a moderate-affinity, uncompetitive antagonist of N- methyl-D-aspartate (NMDA) receptors, is the first non-cholinergic agent approved for the treatment of Alzheimer’s disease (AD), and the first medication approved in the US and Europe for the treatment of moderate to severe stages of the disease. The objective of this study was to analyse safety and tolerability data from phase III memantine trials and from the open-label extensions of those trials.

Method: We conducted an analysis of the pooled data for tolerability and safety from six double-blind, placebo-controlled, memantine trials with a minimum duration of 24 weeks (three trials in mild to moderate AD and three in moderate to severe AD; 20 mg/day; 2311 patients) and four open-label extensions of those trials (two in mild to moderate AD and two in moderate to severe AD; 20 mg/day, 1405 patients), for a total treatment period of up to 2 years.

Results: The analysis revealed that adverse events occurring during both short-and long-term memantine treatment were minimal, and similar in type and frequency to those reported for placebo-treated patients. The most frequently reported adverse events in placebo-controlled trials included agitation (7.5% memantine vs 12.0% placebo), falls (6.8% vs 7.1%), dizziness (6.3% vs 5.7%), accidental injury (6.0% vs 7.2%), influenza-like symptoms (6.0% vs 5.8%), headache (5.2% vs 3.7%) and diarrhoea (5.0% vs 5.6%). Discontinuations due to adverse events were similar in memantine-and placebo-treated groups (8.9% vs 9.8%, respectively).

Conclusion: Consistent with the favourable tolerability profile of memantine observed in clinical use, this analysis of pooled safety data indicates that both short-and long-term memantine treatment of patients with AD is safe and well tolerated, with an adverse event profile similar to that of placebo.

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Acknowledgements

The authors would like to thank Michael Tocco, Scott McDonald, Xinwei Daniel Jia and Hai-An Hsu of Forest Laboratories; Joanne Bell, Jason Olin and Eugene Schneider, formerly of Forest Laboratories; and Vojislav Pejovic and Michael L. Miller of Prescott Medical Communications Group for their contributions to this report. Prescott Medical Communications Group played a role in verifying the accuracy of references and data tables, adjusting the manuscript to the standards of the American Medical Association’s Manual of Style (10th Edition), coordinating the circulation of drafts and edits between authors and preparing the manuscript for journal submission.

Forest Laboratories, Inc. sponsored the design, conduct and analysis of this study and preparation of the manuscript.

Dr Martin Farlow discloses that he receives support from the NIH grant P30 AG10133, and that he has received grants from Eisai, Eli Lilly and Company, Eunoe, Forest, Novartis, Ono/Pharmanet, Pfizer, Sanofi and Syn-X. He also acted as a consultant for Abbott, Accera, Axonyx, Bayer Corporation, Bristol-Myers Squibb, Cephalon, CoMentis, Eisai, Elan Pharmaceuticals, Forest Research Institute, GlaxoSmithKline, Janssen Research Fund, Medivation, Memory Pharm, Merck, NeoTherapeutics, NeuroMolecular, Novartis, OctaPharma, Sanofi-Aventis, Schering-Plough, Talecris Biotherapy and Dr. Willmar Schwabe GmbH and Company, and received honoraria from Eisai, Forest, Novartis and Pfizer as a member of the Speakers’ Bureau. Dr Graham discloses that he is employed by Forest Research Institute. Dr Alva discloses that he has received research support from Forest, Novartis, Pfizer, Janssen, Wyeth, Eli Lilly, BMS-Otsuka, Saegis, Concept Pharmaceuticals, Medivation, Avid Radiopharmaceuticals, AstraZeneca, Organon and Takeda and has received honoraria as a consultant and speaker for Forest, Novartis, Janssen, Pfizer, Abbott, Wyeth, BMS-Otsuka and AstraZeneca.

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Authors and Affiliations

  1. Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive, Indianapolis, Indiana, 46202-5111, USA

    Martin R. Farlow

  2. Forest Research Institute, Jersey City, New Jersey, USA

    Stephen M. Graham

  3. ATP Clinical Research, Costa Mesa, California, USA

    Gustavo Alva

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  1. Martin R. Farlow
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  2. Stephen M. Graham
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  3. Gustavo Alva
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Correspondence to Martin R. Farlow.

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Farlow, M.R., Graham, S.M. & Alva, G. Memantine for the Treatment of Alzheimer’s Disease. Drug-Safety 31, 577–585 (2008). https://doi.org/10.2165/00002018-200831070-00003

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