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Update in General Internal Medicine

John V.L. Sheffield, MD; and Eric B. Larson, MD, MPH
[+] Article, Author, and Disclosure Information

From Harborview Medical Center and Group Health Cooperative, Seattle, Washington.

Potential Financial Conflicts of Interests: None disclosed.

Requests for Single Reprints: Eric B. Larson, MD, MPH, Group Health Cooperative, Center for Health Studies, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.

Current Author Addresses: Dr. Sheffield: Harborview Medical Center, Box 359782, 325 Ninth Avenue, Seattle, WA 98104.

Dr. Larson: Center for Health Studies, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.

Ann Intern Med. 2005;143(3):212-221. doi:10.7326/0003-4819-143-3-200508020-00007
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Our goal for this Update in General Internal Medicine is to update practicing internists on the past year's clinically important research papers. We compiled these articles with the help of general internists and subspecialists from the University of Washington, along with the editors of ACP Journal Club.

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Memantine for moderate to severe Alzheimer's dementia
Posted on September 12, 2005
Sujoy Khan
St. Bartholomew's Hospital
Conflict of Interest: None Declared

Sheffield and Larson*s article *Update in General Internal Medicine* [1] was a good synopsis but new drugs for dementia especially memantine deserved mention. The Cochrane Database Systematic Review is an invaluable source and a recent review on memantine has been published [2]. The New England Journal of Medicine had an important message on memantine: *For the first time, a treatment has been shown to slow the mental and physical decline of patients with moderate to severe Alzheimer's disease (AD) by about six months**[3]. Interestingly, memantine had been marketed in Germany for a decade for neurodegenerative diseases including Parkinson's disease and has recently been approved in both Europe and the USA for the treatment of AD. The daily dose of memantine is 20mg and is an extremely tolerable drug with around 100% bioavailablity. Since its metabolism does not involve the cytochromeP-450 system, the side effects (reported side effects<2%) and interactions are minimal which is advantageous in these patients who already have significant co-morbid medical conditions [4].

Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate and continuous Ca2+influx is implicated in neurodegenerative disorders. This continuous mild activation leads to neuronal damage and impairment of synaptic plasticity (which is important for learning processes) as in AD. Memantine, an adamantine derivative, offers neuroprotection by preferentially blocking excessive NMDA receptor activity without disrupting normal synaptic transmission. Memantine thus serves as a filter blocking *synaptic noise* and allowing detection of relevant signal, which helps to restore synaptic plasticity.

Recent phase III clinical trials have shown that memantine is also effective in the treatment of vascular or multi-infarct dementia and other conditions such as depression, glaucoma and severe neuropathic pain [5]. With increasing robust evidence for memantine, current treatment strategies for dementia will soon undergo major changes.

1. Sheffield and Larson. Update in General Internal Medicine. Ann Intern Med.2005; 143: 212-221. 2. Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev. 2005 Jul 20;(3): CD003154. 3. Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ, Memantine Study Group. Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine 2003 Apr 3; 348(14): 1333-41. 4. Winblad B, Poritis N. Memantine in severe dementia: results of the 9M- Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry. 1999 Feb; 14(2): 135- 46. 5. Lipton SA. Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer's disease and other neurologic disorders. J Alzheimers Dis. 2004 Dec; 6(6 Suppl): S61-74.

Conflict of Interest: None declared

Conflict of Interest:

None declared

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