Donepezil, the first of a new generation of 'rational' treatments for Alzheimer's disease, was licensed for prescription in the UK from April 1997 on the basis of its proven efficacy, as measured by improvement in cognitive function in those receiving treatment.

The improvements documented in the literature are modest. Not all patients improve: roughly one-third continue to decline as expected, one-third maintain their function rather than declining over a period of six months or longer, and up to one-third show improvements.1,2,3

The enthusiasm of families and clinicians has been countered by the doubts of public health physicians and others about the cost implications of prescriptions for such a common condition.4 A year's treatment costs about£1,000.

A debate at the Royal College of Psychiatrists' faculty of old-age psychiatry residential conference in 1997 found that most clinicians were convinced that Donepezil had been demonstrated to have worthwhile potential and should be introduced to routine clinical practice. The preferred mode of introduction would be through assessment, advice and monitoring by a specialist old-age psychiatry service. Similar views were expressed by the British Geriatrics Society and other interested organisations and were eventually supported by the Standing Medical Advisory Committee in 1998.5

But reports suggest that many health authorities have been less enthusiastic about the treatment and that clinicians and families have been frustrated in their attempts to obtain NHS prescriptions for it. We conducted a survey to clarify the present position.

The survey

In May 1998 postal questionnaires were circulated to all consultant old- age psychiatrists on the faculty of old-age psychiatry register. Respondents were asked to provide details of:

purchasing authority;

local experience of prescribing and availability;

characteristics of patients prescribed Donepezil;

accounts of good and bad experiences with it;

view of the status and role of anti-dementia drugs.

A total of 174 responses were received, covering 74 per cent of HAs. There was marked variation between HAs in the number of patients treated (see figure below). In 16 HAs no patients had been treated. Most HAs were treating 10 patients or fewer.

Only 38 per cent of respondents had experience of prescribing in their trusts, while 45 per cent had experience of GP prescribing and 28 per cent knew of private prescribing. Fifty-three per cent used a protocol for who should receive Donepezil and 52 per cent used one to monitor response to the drug.

Who gets the drug?

Most people receiving Donepezil were aged between 65 and 84 with a diagnosis of probable Alzheimer's disease, scored above 10 on the mini mental state examination (MMSE) - a standard measure for cognitive function - and lived with someone (see table opposite). More than two-thirds (69 per cent) of respondents mentioned local campaigning to allow prescribing of the drug. Problems with funding were the main theme. The absence of cost-benefit data was lamented but efforts were being made to persuade HAs to fund anti-dementia drug treatment.

Good experiences with Donepezil

Sixty-two respondents appended comments regarding 'good' experiences with Donepezil (36 per cent of total). These were:

Increased activities (23 comments). A 69-year-old woman previously 'unable to be in kitchen unsupervised' was 'now baking cakes alone', while 'one severely demented lady who scored zero on MMSE began to toilet herself appropriately'. Other comments concerned improvements in patients' ability to perform daily living activities.

Improvement in memory and cognition (14 comments). There were several instances of dramatic increases in MMSE score. There were also reports of increased alertness and concentration (11 comments).

Improved morale or confidence (10 comments).

Improved social behaviour (10 comments).

Improved mood (eight comments).

Improved communication (seven comments).

Clearer thinking (three comments).

Improved sexual relationships (two comments).

Improved driving (two comments).

Bad experiences with Donepezil

Forty-four respondents - relatively few - commented on bad experiences with Donepezil, relating to gastrointestinal disturbance (12 comments), agitation or restlessness (six comments), sleep disturbance (four comments) and dizziness (three).

There were also mixed responses - cognitive improvement but problematic behaviour change (three comments), and other symptoms - headache, urinary symptoms, myoclonus and fit (two comments on each), and stroke, peptic ulceration, flushing and oversedation (one each).

The status and role of the drug

Forty-nine per cent commented on the status or role of anti-dementia drugs. The assessments included:

a modest or limited role (20 comments);

too early for opinion (12 comments);

families or patients deserve access (10 comments);

need for monitoring or evaluation (seven comments) - for example, 'prescribe but on objective protocols which can measure change'.

Other comments concerned the need for funding, the importance of careful diagnosis and non-pharmacological aspects of dementia treatment, the hope that drug treatments offer to carers and patients, the additional workload for old-age psychiatry and primary care, and the effect of drug advertising.


There is little doubt that Donepezil has useful effects on the symptoms of Alzheimer's disease, yet the published evidence does not satisfy the demands of stringent reviewers.6

The clear balance of opinion among clinicians who have been able to prescribe it is that Donepezil has been helpful to many patients and a minority have done spectacularly well. Yet patients' chances of receiving this treatment vary markedly between HAs and between regions. Rationing is being achieved on a massive scale.

The ethics of the present position require urgent review by a dispassionate third party. This medication should be finding its place in the market by the usual process of clinical experience, aided by agreed protocols.

Dr Susan Benbow is consultant in old-age psychiatry, Central Manchester Healthcare trust. Dr Rob Jones is head of the section of old-age psychiatry, Nottingham University. David Jolley is professor in old-age psychiatry, Wolverhampton Healthcare trust.

Key points

A national survey of old-age psychiatrists showed patchy and generally low prescribing of the Alzheimer's drug Donepezil.

Most health authorities had 10 patients, or fewer, on the drug last year.

The ethics of the present position should be examined by a third party.


1 Rogers S, Friedhoff L, Donepezil study group. The efficacy and safety of Donepezil in patients with Alzheimer's Disease: results of a US multi- centre, randomised, double-blind placebo-controlled trial. Dementia 1996; 7: 293-303.

2 Rogers S, Farlow M, Doody R, Mohs R, Friedhoff L. A 24-week double bind placebo controlled trial of Donepezil in patients with Alzheimer's Disease. Neurology 1998; 50: 136-145.

3 Rogers S, Farlow M, Mohs R, Friedhoff L, Donepezil study group. Donepezil improves cognition and global function in Alzheimer's disease. Archives of Internal Medicine 1998; 158: 1021-1031.

4 Melzer D. New drug for Alzheimer's Disease: lessons for health care policy. Br Med J 1998; 316: 762-764.

5 Standing Medical Advisory Committee. The Use of Donepezil for Alzheimer's Disease. Department of Health, 1998.

6 Beppu H, Yanagi M, Hama R. E2020 (Donepezil) in the treatment of cognitive and behavioural disturbances associated with Alzheimer's disease. Cochrane Review, 1998.