Drug treatments for Alzheimer's diseaseBMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7082.693 (Published 08 March 1997) Cite this as: BMJ 1997;314:693
Raise clinical and ethical problems
- Cornelius A Kelly, Consultant senior lecturera,
- Richard J Harvey, Clinical research fellowb,
- Harry Cayton, Executive directorc
- a Mental Health Care For Older People, Department of Psychological Medicine, St Bartholomew's Hospital, Homerton Hospital, London E9 6SR
- b Dementia Research Group, National Hospital For Neurology and Neurosurgery, London WC1N 3BG
- c Alzheimer's Disease Society, London SW1 1PH
Since early January a new treatment for Alzheimer's disease-the acetylcholinesterase inhibitor donepezil-has been available in the United States1 and last week was licensed in the UK. This and possibly other similar compounds will be introduced in the UK and other European countries shortly. Donepezil is the first drug to be licensed in the UK for Alzheimer's disease, and, while its benefits still appear modest, it is easily administered and its side effect profile appears favourable.2 The availability of such drugs does, however, raise clinical and ethical issues.
In 30 week clinical trials a range of cholinesterase inhibitors have been shown to have broadly similar efficacy.2 3 These trials, designed to evaluate symptomatic treatment for Alzheimer's disease, have used two outcome measures: a sensitive measure of cognitive function (ADAS-Cog5) and a global measure of change rated by a clinician independent of the study and blind to all other measures (CIBIC6). Results, on average, have been a 4-6 point difference on the ADAS-Cog scale between treatment and control groups, equivalent to about six months' delay in the course of the disease. Similarly, the independent clinical impression, after six months' treatment, was that significantly more of those treated with the drug showed either no deterioration or an improvement.
Patients included in the clinical trials had to have uncomplicated mild to moderate Alzheimer's disease. Therefore interpreting and applying these findings to the clinical setting is problematic. Only clinical experience with these compounds will indicate their true usefulness. For people with Alzheimer's disease and their carers the benefits of these drugs will be determined by their ability to improve everyday functioning and quality of life.
Cholinesterase inhibitors are a specific treatment for Alzheimer's disease, rather than dementia in general. In recent years the diagnostic challenges have increased with the recognition of dementia of the Lewy body type7 and frontal lobe dementia.8 Definitive diagnosis requires specialised skills, knowledge,9 and investigations such as neuroimaging. A survey of carers of people with dementia showed that the diagnosis of Alzheimer's disease is haphazard and may be made by the patient's general practitioner, a specialist (neurologist, geriatrician, or psychogeriatrician), or not at all.10 The availability of drugs will increase the likelihood of patients coming forward, and trial data suggest that these drugs are most likely to benefit patients early in the disease. Primary care practitioners will have to respond to these patients in new ways.
Treatment protocols will be necessary to ensure an equitable distribution of resources. Currently none exist. Those who develop protocols should ensure wide consultation, particularly with patients and carers. Without coordinated discussion, regional variations in prescribing are likely to develop.
No scientific data exist on the effects of stopping treatment with a cholinesterase inhibitor. Patients who took part in the clinical trials continued to take the active drugs with no defined end point. Without controlled data on long term treatment and treatment discontinuation, the decision to stop the drug may be clinically and ethically difficult to make.
The best available estimate of the costs of providing health and social services to people with Alzheimer's disease in England was £1.1 bn ($1.8 bn).11 Not surprisingly drug expenditure on patients with dementia is low,12 comprising mainly antidepressants, neuroleptics, and hypnotics. The introduction of specific drugs for Alzheimer's disease will increase demand on the drugs budget and shift the burden towards primary health care.
It has been argued that drug treatment for Alzheimer's disease will reduce the need for community support and delay entry into institutional care. One measurable economic outcome examined in open studies of tacrine, an earlier cholinesterase inhibitor, is a delay in institutionalisation. Two American studies suggested that the drug delayed entry into institutional care by up to nine months with an overall saving of 17-30%.13 14 However, delaying institutionalisation may simply shift the burden to the community and families. Moreover, if the drug prolongs the duration of illness then costs will be increased for both health and community services.
The advent of drug treatments for Alzheimer's disease has major implications for the NHS and social services departments as well as patients and their carers. Considerable thought needs to be given to early and accurate diagnosis, the selection of patients most likely to benefit, the impact on primary care, and the overall cost to health and community care budgets. Ethical issues will arise over any lack of equity caused by the use of different treatment protocols, the continuation and discontinuation of treatment, and the impact on the individual and family members of possibly increasing the duration of the illness. We need both more evidence from the use of these drugs in practice and an informed public debate on the issues.
CAK and RJH are both involved in the European arm of the multicentre trial for donepezil.
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