British watchdog National Institute for Clinical Excellence (NICE) has recommended to the National Health Services in England and Wales, that the drugs donepezil (Aricept) rivastigmine (Exelon) and galantamine (Reminyl) should be made available to people with mild to moderate Alzheimer's disease (AD), if a diagnosis of Alzheimer's is confirmed following assessment in a specialist clinic and where the patient has a score of 12 points or above in the mini mental state examination.
The drugs should be made available if the specialist is sure that the person with Alzheimer's is likely to take their medicine regularly. The drug is only continued when a further assessment shows that there has been an increase in, or no decrease in the Mini Mental State Examination (MMSE) score, together with improvements in behaviour and/or functioning.
This is because not all people taking these drugs benefit from them. For those who do not show improvement, or a slowing down of the disease, in the first few months, it is unlikely that they would show any benefit later on and medication should be stopped.
People with Alzheimer's who continue on the drug should have an assessment every 6 months. The drug should normally be given when their MMSE score is above 12 points, and the other tests show that the drug is having a worthwhile effect. When the MMSE score falls below 12 points, patients should not normally be prescribed any of these three drugs. Sometimes drug treatment is stopped for a short period in order to determine whether a person is benefiting from the drug treatment.
Donepezil is marketed by Pfizer/Eisai as Aricept, rivastigmine by Novartis as Exelon and galantamine by Shire Pharmaceuticals and Janssen Cilag as Reminyl. The annual cost of donepezil is £891 (5 mg)/£1,248 (10 mg), taken in a single daily dose, for rivastigmine is £821 (all doses), taken twice per day, and for galantamine is £876 (16 mg)/£1049 (24 mg) (allowing for an initial starting dose of 8 mg daily), taken as 8 mg or 12 mg twice per day.
NICE Chief Executive Andrew Dillon said: "Alzheimer's disease is a very distressing condition and it is clear from the evidence that some patients and their families can benefit from the provision of these medicines. However, it is also important to remind patients and their carers that these products will not benefit all patients and that they should only be used as long as they are having a worthwhile effect. I am certain the guidance will be welcomed by health professionals, patients, and those who care for them."
Alzheimer's is the most common form of dementia. It is a disease that slowly attacks and eventually destroys the parts of the brain that store memory and which carry instructions around the brain (including the chemical messenger acetylcholine).
Research has shown that there is not enough of this chemical in the brains of people with Alzheimer's disease. An enzyme called acetylcholinesterase breaks it down and the drugs donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) can reduce this break down.
Therefore taking one of these drugs may increase the amount of acetylcholine in the brain. Galantamine also enhances the action of acetylcholine on some receptors in the brain. This means that the speed at which the disease develops may be slowed down.
A person with Alzheimer's disease will find that their ability to remember, speak, think and make decisions is affected. These symptoms are common and may not mean that the person experiencing them has Alzheimer's disease.
It is difficult to measure the progress of AD as patients' moods and abilities can vary from day to day, the measuring tools are imprecise, and in some cases the scores rely to a large extent on clinical impression. To find out if someone is suffering from Alzheimer's disease, a health professional observes and records the pattern of symptoms, and uses tests to see what the person can remember. These tests are then repeated a few months later and any change can be measured. For cognitive outcome, MMSE (Mini Mental State Examination) scored out of 30 (where 30 is best), is used.
· Mild Alzheimer's is usually linked to an MMSE score of 21 to 26
· Moderate Alzheimer's is usually linked to an MMSE score of 10 to 20
· Severe Alzheimer's is usually linked to an MMSE score of less than 10
Although these assessments are quite accurate a definite diagnosis of Alzheimer's disease can only be made after death following an examination of the brain tissue.
The total budget impact of the use of these drugs in AD depends on a number of factors, but mostly on the number of patients who would go onto therapy. In the steady state, about 50,000 new cases will be diagnosed each year. However, not all will be diagnosed early enough to have a significant benefit, and not all will be in circumstances where compliance can be reasonably assumed.