Alzheimer's disease: How effective are cholinesterase inhibitors?
Cholinesterase inhibitors can slightly delay the loss of mental abilities in people who have mild to moderate Alzheimer’s disease. But these medications may also cause nausea, vomiting or dizziness.
Alzheimer’s disease is the most common cause of dementia. Nerve cells in the brain start to die and over time memory and the ability to concentrate fade away. Orientation in time and space gets worse, and it is harder to cope with everyday life independently. A person who has Alzheimer’s will need more and more support as time passes.
There is no cure for Alzheimer’s, but there are a number of different medications and other options aiming to relieve the symptoms and slow down the progression of the disease. Available medications for treating Alzheimer’s include cholinesterase inhibitors and memantine, as well as extracts from the leaves of the Ginkgo biloba tree. You can find more information about the effectiveness of these different treatment options on our website.
In people with advanced Alzheimer’s disease, certain nerve cells are 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. Three different cholinesterase inhibitors are currently available in Germany: donepezil, galantamine and rivastigmine. They are taken in the form of tablets. Rivastigmine is now also available in a patch, where it is absorbed through the skin.
Evaluating its effectiveness
Researchers at the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) analyzed controlled trials which looked at the effects of cholinesterase inhibitors in people with Alzheimer’s disease. They were supported by researchers at the universities of Freiburg and Ulm, and at the German Society for International Cooperation (GIZ). In these trials, 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. You can read about why this type of trial improves the quality of the research in our information “Evidence-based medicine.”
Positive effect on mental abilities
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. Some of the people with Alzheimer’s who regularly took one of these medications were able to remember things more easily, for example.
More specifically – taking galantamine as an example – this means that the medication had a positive effect on thinking and memory in about 14 out of 100 people who use it. Galantamine is just one example, and this is not meant to imply that it is better than the other medicines. It is assumed that these different drugs have a similar effect on mental abilities.
The rivastigmine patch is available in different doses. In contrast to the capsules, when rivastigmine is taken using a patch there is only weak evidence that it can improve mental abilities, and this is only for the higher dose of 9.5 mg of rivastigmine released every 24 hours.
Benefits are unclear for many of the other therapy goals
The research done up to now does not show that people with Alzheimer’s can better cope with everyday life by taking cholinesterase inhibitors. It is also not clear that these medications can help with symptoms of dementia such as depression or anxiety.
It has not possible to assess how these medications affect disease-related quality of life, need for nursing home care, or rate of death. It is also not known whether age, sex or accompanying conditions might influence the effects of the drugs.
The IQWiG researchers concluded that based on the latest research none of these three drugs is considered to be superior to the other two. 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 most likely have no effect.
All three medications can cause side effects like nausea, vomiting, loss of appetite, dizziness or diarrhea. These side effects may lead some people to stop the therapy. The higher the dose, the greater the likelihood of adverse effects. Depending on the drug, about 1 to 3 out of 10 people become nauseous or have to vomit.
Rivastigmine patches do not have fewer side effects than the rivastigmine capsules overall, but it causes fewer gastrointestinal problems. It can cause skin redness and itching:
- 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 did not cause any serious side effects. The data from the trials did not have any information about rare side effects or side effects caused only be long-term use.
It also remains unclear how effective cholinesterase inhibitor therapy is over the long term and how it compares to other drug and non-drug therapy options.
Published by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany)
Next planned update: July 2016. You can find out more about how our health information is updated in our text "Informed Health Online: How our information is produced."
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IQWiG health information is based on research in the international literature. We identify the most scientifically reliable knowledge currently available, particularly what are known as “systematic reviews.” These summarize and analyze the results of scientific research on the benefits and harms of treatments and other health care interventions. This helps medical professionals and people who are affected by the medical condition to weigh up the pros and cons. You can read more about systematic reviews and why these can provide the most trustworthy evidence about the state of knowledge in our information “Evidence-based medicine.” We also have our health information reviewed to ensure medical and scientific accuracy.
Institute for Quality and Efficiency in Health Care (IQWiG). Cholinesterase inhibitors in Alzheimer’s disease: Final report; Commission A05-19A. February 7, 2007 [Accessed on: February 6, 2013] (IQWiG Reports; Volume 17). [Executive summary] [Full text]
Institute for Quality and Efficiency in Health Care (IQWiG). Update search on Report A05-19A (Cholinesterase inhibitors in the treatment of Alzheimer's Disease): Rapid report; Commission A09-03. October 12, 2009 [Accessed on: February 6, 2013] (IQWiG Reports; Volume 67). [Executive summary] [Full text – in German]
Institute for Quality and Efficiency in Health Care (IQWiG). Cholinesterase inhibitors in Alzheimer’s disease: supplementary commission rivastigmine patches and galantamine: Final report; Commission A09-05. February 3, 2012 [Accessed on: February 6, 2013]. (IQWiG Reports; Volume 118). [Executive summary] [Full text – in German]