The drug memantine can benefit patients with moderate to severe Alzheimer's disease, according to a study reported in the April 3 New England Journal of Medicine.

Memantine has been used for more than a decade to treat dementia in Germany. Last year, it was approved for treatment of moderate to severe Alzheimer's in other European countries (see ARF related news story), and the manufacturers sought approval for its use in the U.S. (see ARF related news story) and other ARF news story).

The use of memantine for Alzheimer's is based on the theory that excessive activation of N-methyl-D-aspartate (NMDA) receptors may underlie the degeneration of cholinergic cells, leading to cognitive, social, and motor deficits. Memantine, a fast, voltage-dependent NMDA receptor antagonist, blocks the NMDA receptor in the presence of sustained release of low glutamate concentrations, and thus attenuates NMDA receptor function. Theoretically, memantine might protect vulnerable neurons, thus slowing the progression of the disease rather than just providing temporary symptomatic relief, as is thought to be the case with cholinesterase inhibitors.

In the present study, funded by Merz Pharmaceuticals, researchers found benefits after 28 weeks of the double-blind, parallel-group, placebo-controlled study. Relative to the placebo group, patients on memantine had significantly higher scores on a primary test of daily living ability (ADCS-ADLsev) and several secondary tests of function and cognitive performance (FAST and SIB). The authors noted the lack of gastrointestinal side effects seen with cholinesterase inhibitors as another advantage of memantine.

The study design did not provide evidence on whether the symptomatic improvement reflected a slowing of the underlying neurodegeneration. Also, it is impossible to reliably compare the efficacy of memantine directly to that of cholinesterase inhibitors, as studies of the latter drugs have primarily been done in patients with milder disease.-Hakon Heimer.

Reference:
Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ. Memantine in moderate to severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14):1333-41. Abstract

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  1. I read this article in NEJM. Today , is necessary clear some aspects related to aproval by FDA in USA.In EU approved.

    References:
    NEJM april 2003

  2. If memantine was helpful in Germany for over 10 years, then the FDA should speed up its approval for use in the US for Alzheimer's disease. Memantine had no side effects in Germany so how can it have side effects in the US? Let's make memantine available for Alzheimer's patients in the US.

  3. What can we do to hurry FDA along?

    I have sent this info to my Congressman and we are also exploring direct importation.

  4. If you are looking for this drug, it might be available for import with the help of your doctor or you can also get a British doctor to prescribe it through an online pharmacy.

Comments on Primary Papers for this Article

  1. Any glutamate excess in Alzheimer's may be of glial origin. Aldehydic products of lipid peroxidation apparently inactivate glial glutamate uptake transporters. The correct approach to the problem is at a primary level, by correcting the lipid peroxidation with vitamin E, a measure which renders memantine trials completely unnecessary. Long-chain n-3 EFA are also recommended, to replace the marked oxidative loss of these vital synaptic membrane lipids seen in moderate to advanced disease. Primary prevention of the disease itself will first take place in Australia, where the National Institute of Good Health has plans to produce the world's first vitamin E-replete canola oil on a large scale. No mother using such oil in pregnancy will bear an ADHD child, and neither parent will develop Vegetable Oil Syndrome and eventual fullblown AD.

    References:
    Peers RJ (1993) Alzheimer's Disease and Vegetable Oils. NZ Med J, 106;481

    View all comments by Robert Peers

References

News Citations

  1. Memantine Claimed to Augment Donepezil's Effects

Paper Citations

  1. . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14) PubMed.

Other Citations

  1. ARF related news story

Further Reading

Papers

  1. . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14) PubMed.

Primary Papers

  1. . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14) PubMed.