Only five medications have been approved by the U.S. Food and Drug Administration (FDA) for treating Alzheimer's disease (AD). Four of these are called cholinesterase (pronounced ko-lin-ES-tur-ays) inhibitors, and they have been approved for mild to moderate AD. In October 2006, donepezil was also approved for severe AD. The fifth medication is memantine, approved in 2003 for moderate to severe AD.

• Tacrine (Cognex) approved 1993
• Donepezil (Aricept) approved 1996
• Rivastigmine (Exelon) approved 2000
• Galantamine (Reminyl) approved 2001
• Memantine (Namenda) approved in 2003

The cholesterinase inhibitors (donepezil, galantamine, rivastigmine and tacrine) inhibit the metabolism of acetylcholine, a major neurotransmitter (brain messenger) important for memory and thinking. These medications help delay progression of Alzheimer's disease. Cholinesterase inhibitors may also help control some behavioral symptoms. Effective treatment of symptoms of Alzheimer's disease preserves patients' dignity and increases their comfort and independence. These improvements are also appreciated by family members and other caregivers.

Tacrine is very rarely prescribed today because it can cause liver injury, a problem unlikely to occur with the other three cholinesterase inhibitors.

Choosing among the other three cholinesterase inhibitors (donepezil, rivastigmine and galantamine) is a more difficult decision than bypassing tacrine. Choice may be based on physician experience with these medications, the amount of evidence supporting their benefit, side effects, ease of use, individual benefits and cost. When one cholinesterase inhibitor is ineffective, another may still be beneficial. Once improvement is obvious, medication should almost always be continued. Medication discontinuation has been associated with rapid progression of Alzheimer's disease symptoms to the point the person would have reached without treatment.

Compared to placebo, all four cholinesterase inhibitors have been shown to improve memory, thinking and overall functioning. Additional benefits include fewer behavioral disturbances and temporary stabilization of activities of daily living, both of which decrease demands on caregivers. Nursing home placement has also been delayed. Overall, the goals of cholinesterase inhibitor treatment are improvement in thinking and behavior, temporary stabilization of these functions and slowing of the rate of decline.

Memantine, a medication with a different mechanism of action than cholinesterase inhibitors, is approved for the treatment of moderate to severe Alzheimer's disease. It is a partial NMDA receptor blocker that seems to restore a proper balance in the glutamate-NMDA system when it has become too stimulated by glutamate (visit How do medications work in Alzheimer's disease?). Memantine is similar to the cholinesterase inhibitors in that it slows the progression of AD, allowing patients to maintain their overall functioning for a longer period of time. Optimistically, as memantine works on a different brain chemical than cholinesterase inhibitors, doctors may be able to combine it with other AD medications for better results.

Studies in animals show protective effects of memantine against excess glutamate stimulation. In a study of patients with moderate to severe Alzheimer's disease, memantine improved cognitive function and memory significantly more than placebo and memantine had few side effects. Additional studies are underway and are investigating the use of memantine in combination with cholinesterase inhibitors.

• Dosing of FDA-approved Alzheimer’s disease medications
• Side effects of FDA-approved Alzheimer's disease medications

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