Cholinesterase inhibitors for AD 2

§  Reviewer’s conclusions for donepezil: In selected patients with mild or moderate Alzheimer disease treated for periods of 12, 24 and 52 weeks, donepezil produced modest improvements in cognitive function. No improvements were present on patient self-assessed quality of life and data on many important outcomes are not available. Furthermore, the 10mg dose showed only a marginal benefit to the 5mg dose. The practical importance of these changes to patients and caregivers is unclear.[i]

§  Reviewer’s conclusions for galantamine: Patients in these trials were similar to those seen in earlier anti dementia AD trials, and consisted predominantly of mildly to moderately impaired outpatients with AD. Evidence from studies show that there was an overall positive effect for trials of 3, 5 and 6 months in duration.  Furthermore, there was evidence for efficacy of galantamine on global ratings, cognitive tests, assessments of ADLs (activities of daily living) and behaviour. Reviewers stated that the magnitude of cognitive effect was similar to other cholinesterase inhibitors including donepezil, rivastigmine, and tacrine. Also, galantamine's safety profile is similar to that of other cholinesterase inhibitors with regard to cholinergically mediated gastrointestinal symptoms. Longer-term use of galantamine has not been assessed in a RCTs (randomized controlled trials) and is desirable. [ii]

§  Reviewer’s conclusions for Rivastigmine: Studies show that rivastigmine is beneficial for people with mild to moderate AD. In comparisons with placebo, improvements were seen in cognitive function, ADL, and severity of dementia with daily doses of 6 to 12 mg. Further research is needed on dosage (frequency and quantity) in a search for ways to minimize adverse effects.  Moreover, RCTs greater than 26 weeks are needed to determine the efficacy of rivastigmine. [iii]

The cholinesterase inhibitors (donepezil and rivastigime) may not be cost effective for the management of AD [iv] but the study that reached this conclusion has been challenged by the industry which has asserted that it was under powered.  Results of this study were asserted to " … incompatible with many drug company-sponsored observational studies and advertisements claiming remarkable effects of cholinesterase inhibitors" .24  In addition, previous claims that donepezil can stabilize cognitive deterioration and delay nursing home placement by two to three years have not been validated by this study. The study also showed that the long-term use of donepezil cost the UK National Health Service more than placebo.24  The more general understanding is that these drugs do not work in the more severe states of the disease.

Improvements in cognitive functions for the first two years were significantly better than placebo. This validates industry-sponsored studies.  However, no benefits were seen in the long term endpoints of institutionalization, and the experts state that improvements in cognition does not reduce institutionalization as reported by pharmaceutical companies

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[i] Birks J S, Melzer D. Department of Geratology, University of Oxford, Oxford, UK, OX2 6HE. Donepezil for mild and moderate Alzheimer's disease. Cochrane Database Syst Rev. 2000;(2):CD001190.

[ii] Olin J, Schneider L. Adult and Geriatric Treatment and Preventative Interventions Branch, National Institute of Mental Health, NIMH, Room 7160, MSC 9635, 6001 Executive Blvd., Bethesda, Maryland 20892-9635, USA. Galantamine for dementia due to Alzheimer's disease (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.

[iii] Birks J, Grimley Evans J, Iakovidou V, Tsolaki M. Department of Clinical Geratology, University of Oxford, Oxford, UK, OX2 6HE. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2000;(4):CD001191.

[iv] www.scrippharma.com. June 30, 2004. Independent study finds Aricept not cost-effective. Last accessed August 4, 2004.