Although the three drugs work in slightly different ways, the few head-to-head studies of the drugs -- all funded by pharmaceutical companies -- found them equally effective, according to review author Jacqueline Birks of the University of Oxford.
The review appears in the January issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Birks' review included 13 high-quality studies involving 7,298 patients from North America, Europe and Australia. The studies compared the three drugs against placebo treatment, with 2,228 patients in the Aricept studies, 2,267 in the Razadyne studies and 2,803 in the Exelon studies.
The effects of the drugs were not very large when measured across the 13 studies, Birks found. In one measure of how well the drugs worked, for instance, patients across the studies improved by an average of less than three points on a 70-point scale that tracks mental functioning.
"There is nothing to suggest the effects are less for patients with severe dementia, although there is very little evidence for other than mild to moderate dementia," she said.
Side effects caused about 29 percent of the patients taking the drugs to leave the studies, compared with 18 percent dropout among the patients taking a placebo. The most common side effects were nausea, vomiting and diarrhea.
Birks found fewer reported side effects among patients taking Aricept, but she suggests that this may have to do with the way Aricept and the other two drugs are prescribed.
Razadyne and Exelon have a "ramp-up" period in which patients take increasingly higher doses to get to a therapeutic level of treatment. Birks says the two drugs may be as tolerable as Aricept if they are gradually introduced over a course of three months.
In a second review focusing on Aricept only, Birks and researcher Richard Harvey found that a 5 milligram a day dose of the drug was only slightly less effective than a 10 milligram a day dose, with fewer side effects.
In another, newly updated Cochrane review, Dr. Clement Loy of Garvan Institute of Medical Research in Australia and colleagues concluded that Razadyne can improve or maintain mental functioning at a 16 milligram a day dose.
The three drugs are from a class of medicines called cholinesterase inhibitors. They boost chemical signaling in a group of brain neurons that are typically destroyed during the course of Alzheimer's disease.
Birks said there is no way to know ahead of time whether the inhibitors will work on a particular Alzheimer's patient, but some researchers recommend starting the treatment as soon as possible after a diagnosis.
George Grossberg, M.D., a specialist in Alzheimer's treatment at the Saint Louis University School of Medicine, said there is ample evidence that "the earlier one starts the better" for slowing the progression of the disease.
"In fact, patients who come to drugs later, even as little as six months later, never catch up with those who were on drug from the outset," of their diagnosis, Grossberg said.
Although the review of Aricept showed that the drug can be effective even 52 weeks after the start of treatment, Birks says more long term studies of the medicines are needed.
"As Alzheimer's disease generally progresses slowly and clinical course of five to 10 years is not unusual, clinical trials of six or 12 month duration are of limited use," she noted.
Longer trials could also provide more information on whether these drugs are cost-effective treatments. For the moment, there is only limited data on how these drugs affect the overall cost of care for Alzheimer's patients, Birks found.
The review of Aricept was supported by the British National Health Service, University of Melbourne and Barwon Health, Australia.
INTERVIEWS
Contact Jacqueline Birks at +44 1865 224451 or jacqueline.birks@geratol.ox.ac.uk.
Birks J. Cholinesterase inhibitors for Alzheimer's disease. The Cochrane Database of Systematic Reviews 2006, Issue 1.
Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. The Cochrane Database of Systematic Reviews 2006, Issue 1.
Loy C, Schneider L. Galantamine for Alzheimer's disease and mild cognitive impairment. The Cochrane Database of Systematic Reviews 2006, Issue 1.
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 http://www.cochrane.org for more information.