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Rivastigmine for Alzheimer's diseaseBirks J, Grimley Evans J, Iakovidou V, Tsolaki M,
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SummaryRivastigmine is beneficial for people with Alzheimer's disease.Alzheimer's disease (AD) is the commonest cause of dementia affecting older people, and is associated with loss of cholinergic neurons in parts of the brain subserving aspects of memory. Acetylcholinesterase inhibitors, such as rivastigmine, delay the breakdown of acetylcholine released into synaptic clefts and may enhance cholinergic neurotransmission. There is evidence that rivastigmine is beneficial for people with Alzheimer's disease, in being associated with improvements in cognitive function and activities of daily living. Adverse effects were consistent with the cholinergic actions of the drug.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2008 Issue 3, Copyright © 2008 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
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July 26. 1999 AbstractBackgroundAlzheimer's disease (AD) is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of Alzheimer's disease is to enhance cholinergic neurotransmission in relevant parts of the brain by the use of cholinesterase inhibitors to delay the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. Other cholinesterase inhibitors, including rivastigmine, with superior properties in terms of specificity of action and low risk of adverse effects, have now been introduced. Rivastigmine has received approval for use in 60 countries including all member states of the European Union and the USA. ObjectivesTo determine the clinical efficacy and safety of rivastigmine for patients with dementia of Alzheimer's type. Search strategyThe trials were identified from a last updated search of the Specialized Register (SR) of the Cochrane Dementia and Cognitive Improvement Group (CDCIG) on 2 June 2006 using the terms rivastigmine, exelon, "ENA 713" and ENA-713. The CDCIG SR is regularly updated and contains records from all major health care databases and a great many ongoing trial databases. The Internet was searched for unpublished/unreported trials. Selection criteriaAll unconfounded, double-blind, randomized trials in which treatment with rivastigmine was administered to patients with dementia of the Alzheimer's type for more than two weeks and its effects compared with those of placebo in a parallel group of patients. Data collection and analysisOne reviewer (JSB) applied study selection criteria, assessed the quality of studies and extracted data. Main resultsEight trials, involving 3660 participants, were included in the analyses. Use of rivastigmine in high doses was associated with statistically significant benefits on several measures. High-dose rivastigmine (6 to 12 mg daily) was associated with a 2.1 point improvement in cognitive function on the ADAS-Cog score compared with placebo (weighted mean difference -2.09, 95% confidence interval -2.65 to -1.54, on an intention-to-treat basis) and a 2.2 point improvement in activities of daily living assessed on the Progressive Deterioration Scale (weighted mean difference -2.15, 95% confidence interval -3.16 to -1.13, on an intention-to-treat basis) at 26 weeks. Fewer patients were graded as having severe dementia at 26 weeks (55% of patients taking rivastigmine compared with 59% on placebo; odds ratio 0.78, 95% confidence interval 0.64 to 0.94). At lower doses (4 mg daily or lower) differences were in the same direction but were statistically significant only for cognitive function. There were statistically significantly higher numbers of events of nausea, vomiting, diarrhoea, anorexia, headache, syncope, abdominal pain and dizziness among patients taking high-dose rivastigmine than among those taking placebo. There was some evidence that adverse events might be less common with more frequent, smaller doses of rivastigmine. Authors' conclusionsRivastigmine appears to be beneficial for people with mild to moderate Alzheimer's disease. In comparisons with placebo, improvements were seen in cognitive function, activities of daily living, and severity of dementia with daily doses of 6 to 12 mg. Adverse events were consistent with the cholinergic actions of the drug. Further research is desirable on dosage (frequency and quantity) in a search for ways to minimize adverse effects. This review has not examined economic data. |