Cholinesterase inhibitors for Alzheimer's disease

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Examples

Brand Name Chemical Name
Aricept donepezil
Razadyne galantamine
Exelon rivastigmine


How It Works

Cholinesterase inhibitors increase the level of a brain chemical called acetylcholine. People with Alzheimer's disease and related conditions have decreased brain levels of this neurotransmitter. Increasing the amount of acetylcholine appears to slow mental decline in people with Alzheimer's disease.

These medications help the brain cells work better but do not stop or reverse the destruction of brain cells and loss of acetylcholine that occur in Alzheimer's disease. They do not prevent the disease from getting worse but may slow the progression of symptoms.


Why It Is Used

Cholinesterase inhibitors may be used to treat some symptoms of moderately severe Alzheimer's disease. They also may be used in other types of dementia, such as dementia with Lewy bodies and multi-infarct dementia.


How Well It Works

Cholinesterase inhibitors may produce small improvements in memory and general ability to function.1 For example, the person may be able to remember friends' names better and be able to dress himself or herself with less difficulty. They may also modestly improve behavioral symptoms and improve the person's ability to function.2

* Studies have shown that people with mild to moderately severe Alzheimer's who took donepezil scored somewhat higher in their doctors' evaluations of their mental and functional status than those who did not take the drug.
* Studies show that rivastigmine has beneficial effects similar to donepezil. Rivastigmine has more side effects, including nausea and possible weight loss. Rivastigmine does not appear to cause interactions with other medications, as the other cholinesterase inhibitors do.3
* Galantamine is available in the United States. It may improve memory and thinking abilities.
* Improvement with cholinesterase inhibitors usually is minimal. The person's mental status does not stabilize, but the rate of decline may be somewhat slower than it would be without the medication.
* Improvement in symptoms may be more likely at higher doses, but higher doses also may cause more side effects.
* Cholinesterase inhibitors may improve behavioral disturbances. People who have improved thinking and memory abilities may also have improved behavior, although this is not always the case.
* Cholinesterase inhibitors may have some use in other dementias, such as dementia with Lewy bodies and multi-infarct dementia.

Cholinesterase inhibitors do not help everyone who has Alzheimer's disease. It is believed that as the disease progresses, the medication eventually may stop working.

The various cholinesterase inhibitors have similar effects on memory and cognitive function, so the choice between medications may be based on side effects, dosing schedules and ease of use, individual response to a particular medication, or other factors.


Side Effects

In general, most people seem to tolerate cholinesterase inhibitors very well. The most common side effects are:

* Nausea.
* Diarrhea.
* Vomiting.
* Indigestion.
* Abdominal pain.
* Loss of appetite and weight loss.

Less common side effects include insomnia, fatigue, and muscle cramps. Side effects tend to be mild and usually go away within a few weeks after treatment with the medication is started.

See [individual drug listings] for a full list of side effects of each.


What To Think About

Cholinesterase inhibitors do not work for everyone who has Alzheimer's disease, but they are helpful for some people. They may be a reasonable option for those who understand the risks and costs and feel the possible benefits are worth it.

A study that compared the results of other studies looking at cholinesterase inhibitors for people with Alzheimer's disease found that the benefits of taking them are small.4

Side effects seem to be milder and occur less often with donepezil or galantamine than with rivastigmine.

Experts agree that reducing problems with memory loss may help people with Alzheimer's disease live better. In some cases, reducing these problems may help people live more independently for a longer period of time.

Rivastigmine (Exelon) can now be given through a skin patch. Skin patches release medicine into the blood at a steady level and may reduce side effects. And it’s easier for caregivers to make sure a person is taking the medicine properly when the person uses a skin patch.


References

Citations

1. Bentham P, et al. (2004). Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): Randomised double-blind trial. Lancet, 363(9427): 2105–2115.
2. Trinh NH, et al. (2003). Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: A meta-analysis. JAMA, 289(2): 210–216.
3. Warner J, et al. (2005). Dementia. Clinical Evidence (14): 1198–1220.
4. Kaduszkiewicz H, et al. (2005). Cholinesterase inhibitors for patients with Alzheimer's disease: Systematic review of randomised clinical trials. BMJ, 331(7512): 321–327.

Credits
Author Sabra L. Katz-Wise
Author Ralph Poore
Editor Susan Van Houten, RN, BSN, MBA
Associate Editor Pat Truman
Primary Medical Reviewer Adam Husney, MD
- Family Medicine
Primary Medical Reviewer Kathleen Romito, MD
- Family Medicine
Specialist Medical Reviewer Peter J. Whitehouse, MD
- Neurology
Last Updated November 15, 2006