Newswise — Sometimes less is more: Lower doses of an Alzheimer's drug delivered via skin patches improve cognition with fewer serious side effects than higher doses, researchers have found in an updated review.

"Is there any advantage of giving patients higher doses of rivastigmine? There doesn't seem to be any," said lead review author Jacqueline Birks, senior medical statistician for the University of Oxford, in England.

Previous studies had shown that high daily doses of rivastigmine (also known by its brand name, Exelon) of between 6 and 12 milligrams improved cognitive functions, such as memory, language and ability to perform simple daily living tasks, in patients with mild to moderate Alzheimer's disease.

However, adverse events often accompany high doses of rivastigmine.

Rivastigmine is part of the drug class called acetylcholinesterase inhibitors. These drugs work by improving transmission of electrical signals across certain areas of the brain.

Manufactured by Novartis, rivastigmine typically causes gastrointestinal side effects such as nausea, vomiting, diarrhea, abdominal pain and lack of appetite, as well as dizziness, fainting and weakness. In the United States, the drug costs about $160 per month.

Previous studies indicated that smaller, more frequent doses of rivastigmine might reduce the incidence of adverse events. Based on that evidence, a new study, the results of which are included in the update, began testing the safety and effectiveness of two strengths of the rivastigmine skin patch.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The current review examined nine studies involving 4,775 patients with Alzheimer's disease. Research in five of the studies took place in the United States.

"What I was really interested in was how the [smaller 9.6 milligram/day] patch compared to the [larger 17.4 milligram/day] patch. What I found was that there didn't seem to be any differences in efficacy, but the patch in higher doses has more adverse events associated with it," Birks said.

Patients taking the larger patch scored similarly on cognitive function tests, compared to those taking the smaller patch, but two-thirds of patients taking the larger patch had at least one adverse event, compared to only half of patients taking the smaller patch.

For example, 19 percent of those taking the larger patch reported vomiting, whereas only 6 percent of patients taking the smaller patch reported this side effect.

"Gastrointestinal adverse events are associated with acetylcholinesterase inhibitors, but we see fewer with the smaller patch compared with the larger patch," Birks noted.

Patients taking the smaller rivastigmine patch also had lower rates of adverse events when compared to patients taking a 6- to 12-milligram daily dose of rivastigmine capsules, Birks said.

"It seems to show that they have improved the method of administering rivastigmine. We seem to get the same efficacy but we have a better adverse event profile" with the smaller dose patch, Birks said.

"This review has confirmed what we knew about the drug — that it provides cognitive improvements similar to other Alzheimer's medications, said Piero Antuono, M.D., a professor of neurology, pharmacology and toxicology at the Medical College of Wisconsin.

He has no affiliation with the review.

"Over a period of six months, people with Alzheimer's who take this drug improve by two points on a cognitive scale of zero to 70. If untreated, people with Alzheimer's lose an average of seven points per year," Antuono said.

Although acetylcholinesterase inhibitors such as rivastigmine do affect cognitive function in people with Alzheimer's, patients and their caregivers should understand that these drugs do not change the ultimate progression of this degenerative disease, he said.

"It's changing a little bit of the journey of the disease. You either take the expressway from point A to point B, or with this medication, you slow down and take the country road. It doesn't really make a difference long term, and it doesn't prolong life," Antuono said.

"Although these medications do provide symptomatic intervention for some time, they have to be used with non-pharmacological interventions, meaning that one needs to counsel the caregiver in managing the patient and provide social support so that the drug gets to work," Antuono said.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit for more information.

Birks J, et al. Rivastigmine for Alzheimer's disease. The Cochrane Database of Systematic Reviews 2009, Issue 2.

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