Memantine

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Memantine

Purpose

Memantine HCl (trade name Namenda) is an N-methyl-D-aspartate (NMDA) receptor antagonist used to treat moderate to severe Alzheimer’s disease (AD).

A recent theory concerning the mechanism underlying AD is that abnormal glutamate activity in the brain causes overexcitation of NMDA receptors, which may play a role in the development and progression of AD. Memantine is a NMDA-receptor antagonist, which hypothetically allows the continued physiological activation of NMDA receptors for continued learning and memory. However, memantine does not appear to prevent or slow the degeneration of brain cells in patients with AD.

Randomized, double-blind, placebo-controlled clinical trials of memantine have demonstrated significant improvement of day-to-day functioning in moderate to severe AD.

Recommended dosage

Memantine is available in tablet form, or as an oral solution for patients who have difficulty swallowing tablets. Typically, patients are gradually put on mematine by taking 5 mg once a day for the first week, 5 mg twice a day for the second week (10 mg total per day), and 10 mg in the morning and 5 mg in the evening for the third week (15 mg total per day). After that, the maintenance dosage of memantine is 10 mg twice a day (20 mg total per day). Memantine can be taken with or without food.

Precautions

Clinical trials of memantine found it to be safe and well tolerated. However, anyone with a known hyper-sensitivity to memantine HCl or any of the inert substances used as a vehicle for the drug should not take memantine. The dosage of memantine should be reduced for patients with severe kidney impairment.

Side effects

No significant difference has been found between patients taking memantine and patients taking a placebo in vital signs, electrocardiogram values, or laboratory values (serum chemistry, hematology, and urinalysis). The most common adverse reactions to memantine are:

dizziness
confusion
headache
constipation
agitation
falling
accidental injury Compared with placebo, memantine showed a lower level of gastrointestinal side effects (such as constipation, diarrhea, vomiting, or nausea).

Interactions

Studies have revealed that the use of memantine in combination therapy with donepezil, a cholinesterase inhibitor, is frequently more effective than the use of donepezil alone in the treatment of moderate to severe AD. Using memantine and donepezil in combination therapy does not affect the actions of either drug. Memantine has been shown to be both safe and effective in such combination therapy.

Studies on memantine have shown low potential for negative interaction with other drugs.

KEY TERMS

Alzheimer ’s disease—Alzheimer’s disease (AD) is a progressive neurologic disease in which dementia results from the degeneration of brain cells through the formation of senile plaques and neuro-fibrillary tangles. AD is the most common cause of dementia.

Clinical trial —A controlled scientific experiment designed to investigate the effectiveness of a drug or treatment in curing or lessening the symptoms of a disease or disorder.

Control group —A group in a research study that does not receive the experimental treatment. For example, in an experiment testing the effectiveness of a new drug, the control group might receive the current drug of choice while the experimental group receives the new drug under investigation.

Double-blind study —A research study in which neither the participants nor the professional giving them the drug or treatment know whether they are receiving the experimental treatment or a placebo or control treatment.

Placebo —A preparation without pharmacological effect that is given in place of a drug in clinical trials to determine the effectiveness of the drug under study; a “sugar pill.”

Randomization —The process of randomly assigning participants in an experiment to the various conditions (that is., experimental and control groups) so that each individual has an equal chance of being assigned to any of the groups. Randomization helps ensure that each of the groups is roughly the same and that the results are due to the treatment, not to the makeup of the groups.

Resources

BOOKS

Burns, Alistair, and Bengt Winblad, eds. Severe Dementia. New York: John Wiley & Sons, 2006.

VandenBos, Gary R., ed. APA Dictionary of Psychology. Washington D.C.: American Psychological Association, 2006.

PERIODICALS

Alexopoulos, G. S., D.V. Jeste, H. Chung, D. Carpenter, R. Ross, and J. P. Docherty. “Treatment of Dementia and Its Behavioral Disturbances. Introduction: Methods, Commentary, and Summary.” Postgraduate Medicine Jan. 2005: 6–22.

Cummings, Jeffrey L., Eugene Schneider, Pierre N. Tariot, and Stephen M. Graham. “Behavioral Effects of Memantine in Alzheimer Disease Patients Receiving Donepezil Treatment.” Neurology 67.1 (2006): 57–63.

Danysz, W., C. G. Parsons, J. H. Mobius, A. Stoffler, and G. Quack. “Neuroprotective and Symptomalogical Action of Memantine Relevant for Alzheimer’s Disease: A Unified Glutamatergic Hypothesis on the Mechanism of Action.” Neurotoxicity Research2 (2000):85–97.

Doody, R. S. “Refining Treatment Guidelines in Alzheimer’s Disease.” GeriatricsJune 2005: 14–20.

Doraiswamy, P. M. “Non-Cholinergic Strategies for Treating and Preventing Alzheimer’s Disease.” CNS Drugs 16 (2002): 811–24.

Fox, Chris, Ian D. Maidment, Malaz Boustani, and Cornelius Katona. “Memantine Combined with an Acetyl Cholinesterase Inhibitor—Hope for the Future?”Neuropsychiatric Disease And Treatment 2.2 (2006): 121–25.

Hartmann, S., and H. J. Möbius. “Tolerability of Memantine in Combination with Cholinesterase Inhibitors in Dementia Therapy.” International Clinical Psycho-pharmacology 18 (2003): 81–85.

Maidment, Ian, Chris Fox, Gill Livingston, and Cornelius Katona. “Drug Treatment for Alzheimer’s Disease: The Way Forward.” International Journal of Geriatric Psychiatry 21.1 (2006): 6–8.

Orgogozo, J. M., A. S. Rigaud, A. Stoffler, H. J. Mőbius, and F. Forette. “Efficacy and Safety of Memantine in Patients with Mild to Moderate Vascular Dementia.” Stroke33 (2002): 1834–39.

Reisberg, B., R. Doody, A. Stőffler, F. Schmitt, S. Ferris, and H. J. Mőbius. “Memantine in Moderate-to-Severe Alzheimer’s Disease.” New England Journal of Medicine, 348 (2003): 1333–41.

Tariot, Pierre N., Martin R. Farlow, George T. Grossberg, Stephen M. Graham, Scott McDonald, and Ivan Ger-gel. “Memantine Treatment in Patients with Moderate to Severe Alzheimer Disease Already Receiving Donepezil: A Randomized Controlled Trial.” Journal of the American Medical Association291 (2004): 317–24.

Xiong, G., and P. M. Doraiswamy. “Combination Drug Therapy for Alzheimer’s Disease: What Is Evidence-Based, and What Is Not?” Geriatrics 60.6 (2005): 22–26.