| With the increasing prevalence of dementia, there has been a large
amount of research into trying to elucidate the neuropathology of
various dementias, but most particularly Alzheimer's disease, which
is the most common. As research continues and more details of the
various pathological processes become clearer, new avenues for the
treatment of Alzheimer's disease will become available. Currently,
most research has focused on the known fact that people dying from
Alzheimer's disease have a reduction in acetylcholine and choline
acetyl transference. This has led to the hope that treatment by
increasing acetyl choline at synapses will have beneficial effects.
This is similar to the precursor treatment in Parkinson's disease.
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 is the director of the Rehabilitation and Geriatric Service, Richmond Health Service, Lismore, NSW 2480, Australia.
* Donepizil is now available on the PBS.
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