How effective are cholinesterase inhibitors?

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Cholinesterase inhibitors can slightly delay the loss of brain function in people who have mild to moderate Alzheimer’s disease. But these medications may also cause side effects such as nausea, vomiting or dizziness.

There is no cure for Alzheimer’s, but there are a number of different medications and strategies aiming to relieve the symptoms and slow down the progression of the disease. Non-drug strategies include memory training and the encouragement of social activities. The medications available for treating Alzheimer’s include cholinesterase inhibitors and memantine, as well as the herbal medicine Ginkgo biloba.

Cholinesterase inhibitors

In people with advanced Alzheimer’s disease, certain nerve cellsare much less active. This means that it takes longer for brain signals to be sent. Cholinesterase inhibitors aim to increase communication between the nerve cells to try to improve the symptoms of Alzheimer’s. These drugs have been approved for use in mild to moderate Alzheimer’s disease. In Germany, three different cholinesterase inhibitors are currently available: donepezil, galantamine and rivastigmine. They are taken in the form of tablets. Rivastigmine is also available in a patch. Here the drug is absorbed into the body through the skin.

How well do they work?

Various systematic reviews analyzed the results of controlled studies on the effectiveness of cholinesterase inhibitors in people with Alzheimer's disease. In these studies, either one group of participants took one of the three cholinesterase inhibitors and a control group took a placebo (a dummy treatment), or the drugs were compared directly with each other. The researchers wanted to see whether the medication improved people’s mental (cognitive) performance, reduced mental health problems or made it easier for them to perform daily tasks. There are many good-quality studies on these effects, so it's possible to properly assess the short-term advantages and disadvantages. But most of these studies lasted for six months at the most, so it's difficult to see what the effects of long-term use would be.

Positive effect on cognitive performance

The studies show that the cholinesterase inhibitors donepezil, galantamine and rivastigmine can slightly delay the loss of mental abilities in people who have mild to moderate Alzheimer’s disease. For instance, some of the people with Alzheimer’s who regularly took one of these medications were able to remember things more easily.

More specifically, taking the example of galantamine: The medication has a positive effect on thinking skills and memory in about 14 out of 100 people who use it. Galantamine is just used as an example here, and this is not meant to imply that it is more effective than the other medicines. It is believed that the different drugs have a similar effect on cognitive performance.

The rivastigmine patch is available in different doses. Unlike rivastigmine capsules, there is only weak suggesting that the patch improves cognitive performance. And this weak effect was only observed with the higher dose of 9.5 mg of rivastigmine released every 24 hours.

Benefits are unclear regarding many of the other therapy goals

So far, the research hasn't shown that cholinesterase inhibitors help people with Alzheimer’s cope better in everyday life. It's also not clear whether these medications can help with mental health problems associated with Alzheimer's, such as depression or anxiety.

It hasn't yet been possible to tell whether the drugs can improve disease-related quality of life and delay the move to a nursing home. It is also not known whether age, sex or accompanying conditions might influence the effects of the drugs.

None of the three substances can be said to be better than the others. All three cholinesterase inhibitors were found to have a stronger effect when taken in moderate to high doses than when taken in very low doses. However, donepezil already has an effect in smaller doses, whereas small doses of galantamine and rivastigmine probably don't.

Side effects

All three medications can cause side effects like nausea, vomiting, loss of appetite, dizziness or diarrhea. Some people might stop taking them as a result. Higher doses are more likely to cause side effects. Depending on which medication they take, about 1 to 3 out of 10 people feel nauseous or vomit.

Rivastigmine patches do not generally have fewer side effects than the rivastigmine capsules, but the patch causes fewer gastrointestinal problems. It can cause skin redness and itching, though:

  • About 13 out of 100 people have skin redness due to the patch.
  • About 10 out of 100 people have itching due to the patch.

The medications didn't cause any serious side effects. The data from the studies didn't provide any information about rare side effects or side effects that only occur after long-term use.

It is also not clear what sort of long-term benefits cholinesterase inhibitors may have, or how they compare to other medications or non-drug treatment options.

Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Cholinesterase inhibitors in Alzheimer's disease: Final report; commission A05-19A. February 07, 2007. (IQWiG reports; Volume 17).

Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Update search on report A05-19A (cholinesterase inhibitors in the treatment of Alzheimer's Disease) 2009.

Strohle A, Schmidt DK, Schultz F, Fricke N, Staden T, Hellweg R et al. Drug and Exercise Treatment of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Effects on Cognition in Randomized Controlled Trials. Am J Geriatr Psychiatry 2015; 23(12): 1234-1249.

IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. informedhealth.org can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

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Updated on June 29, 2017
Next planned update: 2021

Authors/Publishers:

Institute for Quality and Efficiency in Health Care (IQWiG, Germany)

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