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Alzheimer's Treatment

Two years ago, Tacrine was introduced to Australia and was available, but not as part of the pharmaceutical benefits scheme. Tacrine had serious side effects, particularly on the liver and gastro-intestinal tract, with a side effect rate in the order of 50 per cent. The other problem was its qid dosage in people who are forgetful! Clinical studies showed that, in perhaps five to 10 per cent, there was some benefit, but the serious side effects, the dosage regime and its cost meant that it was not a very successful, or user acceptable medication.

The latest medication to be introduced, but still not on the PBS, is Donepezil (Aricept), an anti-cholinesterase inhibitor. Its main advantage is that it is over 1000 times a more potent inhibitor of acetyl cholinesterase, which is predominantly in the central nervous system, than Butyryl cholinesterase, which is mainly outside the CNS. As a result, Donepezil has very little in the way of side effects. Its other main advantages are that it is only a once daily dosage with a half life of about 70 hours. A steady state is reached in about three weeks. The standard dose is 5mgs daily and after one month, this can be increased to 10mgs. Research shows that doses in excess of 10mgs provide no advantage.

Although Donepezil is metabolised by the Cytochrome P450 System, it does not seem to cause any major interactions with Cimetidine or Digoxin. The main side effects are gastro-intestinal with mainly nausea or increased bowel frequency. So far, in Australia, no-one beginning the drug has had to stop because of its side effects.

As Donepezil is not in the PBS, it is available through the SAS scheme. Currently, it is possible to obtain the medication through Pfizer. It is indicated for those people suffering from Alzheimer-type dementias. It is not indicated for those with multi-infarct or other types of dementia, or people who think they are forgetful! It has an indication for those with mild to moderate Alzheimer's disease.

Research with Tacrine indicates that it may be helpful in those people with frontal changes associated with Alzheimer's disease. The theory is that there is an increase in acetyl choline at post synaptic neurones that have not died back. Therefore, it may be helpful in some of those people with behavioural problems as well as those with memory problems. However, the research so far has been very preliminary, but no doubt with this more acceptable medication, more research will be forthcoming.

Personally I have started about 10 people on Aricept since the beginning of October and have no other experience of its benefits, acceptability or side effects at this time.

As more research is undertaken, more drugs for the treatment of Alzheimer's disease will become available and Aricept is fortunate to be the forerunner in what will be quite a pack over the next few years. In spite of this, one must remain cautious as to whether this approach in medication is really going to be beneficial. This is partly because of the difficulties with precise diagnosis. However, this is a nice step in the right direction and it is nice to be able to offer people a trial of treatment with a medication that is simple to take, low in side effects and cheap at $30 a month.

Hugh Fairfull-Smith Director, Rehabilitation and Geriatric Service

Richmond Health Service