J Clin Pharmacol
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ARTICLES

Rationale for Combination Therapy With Galantamine and Memantine in Alzheimer's Disease

George T. Grossberg, MD, Keith R. Edwards, MD and Qinying Zhao, PhD

From the Division of Geriatric Psychiatry, Saint Louis University, St. Louis, Missouri (Dr Grossberg); the Department of Neurology, Beth Israel Deaconess Medical Center, Boston (Dr Edwards); and Johnson & Johnson Pharmaceutical Research & Development LLC, Titusville, New Jersey (Dr Zhao).

ABSTRACT

A combination of cholinergic and glutamatergic dysfunction appears to underlie the symptomatology of Alzheimer's disease. Therefore, one hypothesis is that treatment strategies should address impairments in both systems. Galantamine is an acetylcholinesterase inhibitor that, unlike other acetylcholinesterase inhibitors, has a postulated dual mode of action as a nicotinic receptor modulator. Galantamine has demonstrated long-term efficacy in improving or maintaining cognition, functionality, and behavior in patients with mild to moderate Alzheimer's disease. Memantine, a noncompetitive N-methyl-D-aspartate-receptor antagonist, reduces deterioration in cognition and function in patients with moderate to severe Alzheimer's disease. Pharmacokinetic and pharmacodynamic as well as ongoing observation studies support the concept of adjunctive therapy with memantine in patients with advanced moderate Alzheimer's disease currently treated with an established galantamine regimen. The potential to modulate both acetylcholine and glutamate pathways in Alzheimer's disease presents a novel treatment strategy for the management of mild to moderately severe Alzheimer's disease.

Key Words: Alzheimer's disease • combination therapy • galantamine • memantine • donepezil

Address for reprints: George T. Grossberg, MD, Division of Geriatric Psychiatry, Department of Psychiatry, Saint Louis University, 1221 S. Grand Boulevard, St. Louis, MO 63104; e-mail: grossbgt{at}slu.edu.






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