Letters

Drugs for Alzheimer's disease

BMJ 2001; 323 doi: http://dx.doi.org/10.1136/bmj.323.7321.1127/a (Published 10 November 2001) Cite this as: BMJ 2001;323:1127

More effective agents are needed

  1. James Warner, senior lecturer in old age psychiatry,
  2. Rob Butler, consultant in old age psychiatry
  1. Faculty of Medicine, Imperial College of Science, Technology and Medicine, London W10 6DZ
  2. St Margaret's Hospital, Epping CM16 6TN
  3. Department of Geriatric Medicine, Royal Perth Hospital, Perth, WA 6000, Australia

    EDITOR—O'Brien and Ballard in their editorial outlined the approval by the National Institute for Clinical Excellence of cholinesterase inhibitors for the treatment of mild to moderate Alzheimer's disease.1 We believe, however, there are limitations in the evidence of the efficacy of cholinesterase inhibitors that should be considered.

    Pharmaceutical companies have sponsored most of the studies so far, which may lead to overestimation of the effect size.2 Many studies have been conducted in selected samples in secondary care, and the drugs may be less effective in the wider population. Most studies used “intention to treat” analyses (all randomised cases are included in the results, whether they completed the study or not) with “last observation carried forward” (including the last observation as the final result). Since people with dementia tend to get worse over time, those leaving a study early will carry forward artificially “better” results. People taking effective doses of cholinesterase inhibitors tend to drop out more often than those in the placebo arm, which leads to overestimation of the treatment effect.

    The current standard measure of efficacy in dementia studies is the 70 point cognitive subsection of the Alzheimer's disease assessment scale (ADAS-cog). This and similar measures of cognition may miss some of the effects of the cholinesterase inhibitors and underestimate the true effects of these drugs. The current evidence suggests the numbers needed to treat for a 4 point improvement on the ADAS-cog subscale are four for donepezil, seven for galantamine, and 17 for rivastigmine.3

    We agree that these drugs have led to a new mood of optimism, but more effective agents may be necessary to deliver the results.

    References

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    Guidelines for prescribing cholinesterase inhibitors in Australia are similar to those in UK

    1. Jane M Noble, specialist registrar in geriatric and general medicine (jane.noble{at}health.wa.gov.au)
    1. Faculty of Medicine, Imperial College of Science, Technology and Medicine, London W10 6DZ
    2. St Margaret's Hospital, Epping CM16 6TN
    3. Department of Geriatric Medicine, Royal Perth Hospital, Perth, WA 6000, Australia

      EDITOR—O'Brien and Ballard discuss the use of cholinesterase inhibitors for the palliation of Alzheimer's disease, in particular mentioning issues of cost effectiveness and rationing.1 As a British specialist registrar in geriatric medicine currently gaining experience in Australia, I am interested in the Australian experience of prescribing cholinesterase inhibitors.

      In Western Australia geriatric physicians rather than psychogeriatricians manage patients with dementia. Two cholinesterase inhibitors, donepezil and rivastigmine, are licensed by the Pharmaceutical Benefits Scheme. Strict guidelines exist for their prescription2: a consultant geriatrician or psychogeriatrician must confirm the diagnosis of Alzheimer's disease, and patients must score between 10 and 24 on the standardised mini-mental state examination; patients who score ≥25 but have clinical features of Alzheimer's disease should be evaluated further by the cognitive subsection of the Alzheimer's disease assessment scale (ADAS-cog). The only exceptions to this rule are patients who received cholinesterase inhibitors on private prescription before December 2000; they may continue with treatment indefinitely, using the Pharmaceutical Benefits Scheme's subsidised prescriptions.

      The Pharmaceutical Benefits Scheme allows a six month prescription of donepezil or rivastigmine on a named patient basis. To continue to receive subsidised prescriptions beyond six months, patients must show improvement of ≥2 points on the mini-mental state examination (or a reduction of 4 points on the ADAS-cog), measured at any time over the initial prescription period.

      Memory clinics are being established throughout Australia to facilitate the assessment and treatment of patients with cognitive impairment. Although the primary aim of these clinics is to evaluate patients' eligibility for cholinesterase inhibitors, they may also result in a fuller multidisciplinary assessment of patients with dementia.

      The Australian guidelines are similar to those outlined by the National Institute for Clinical Excellence. Both guidelines address the question of how to measure response and ensure that patients with advanced dementia and non-responders are not treated unnecessarily. The United Kingdom's guidelines also tackle the problem of when to stop treatment. With time, experience will be gained in the management of other difficult issues, such as how to manage patients who report a clinical response (or whose family does) but who fail to show the required improvement on the mini-mental state examination.

      References

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      View Abstract