Memantine: A New Treatment Option for Patients with Moderate-to-Severe Alzheimer’s Disease

Ho Y and Chagan L (March 2004). P&T 29.

Alzheimer’s disease (AD) affects approximately 15 million people worldwide and more than four million Americans in the U.S. alone. This disease targets the elderly population, and the incidence increases with age. Women are at a higher risk for AD, whereas men tend to develop vascular dementia. AD progresses slowly and results in impairment of both cognitive and functional capacities. A gradual loss of neurons is responsible for the decline in memory, physical functioning, learning, behavior, and reasoning. Depending on the symptoms displayed, AD is classified as mild, moderate, or severe. In patients with AD, certain areas of the brain, including the hippocampus and the amygdala, are vulnerable to the degenerative changes. Although the pathophysiology of AD is not completely understood because of the involvement of the various neuronal pathways, it is thought that the disease’s presentation is linked to changes in catecholaminergic, serotonergic, and cholinergic transmissions. The involvement of multiple neuronal pathways acts as a barrier to selecting the appropriate treatment. Until recently, the only available drugs on the market for AD included the cholinesterase inhibitors, such as galantamine donepezil HCl (Aricept®, Esai/ Pfizer), rivastigmine tartrate (Exelon®, Novartis), and tacrine HCl (Cognex®, Pfizer). These drugs, which have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild-to-moderate disease, help to increase the concentration of acetylcholine (AcH) by inhibiting the enzyme acetylcholinesterase, which is responsible for hydrolyzing AcH. These therapies do not halt disease progression but have been shown to benefit cognition, function, and behavior in short-term and long-term placebo-controlled studies. A new approach to slow the progression of AD has been under investigation. Memantine (Namenda^TM, Forest), an N-methyl-D-aspartate (NMDA) receptor antagonist, was approved in October 2003 to treat moderate-to-severe dementia of the Alzheimer’s type and is now on the U.S. market. Memantine is not a new drug; it has been available from Merz in Germany for the treatment of dementia since 1982. Its mechanism of action has been shown to be both safe and efficacious in improving performance in patients with moderate-to-severe AD.