Individual nerve cells communicate with one another
through the release of a chemical called acetylcholine.
Once acetylcholine, a neurotransmitter, has done its
job, it is eliminated by an enzyme called
acetylcholinesterase. Aricept, Reminyl and Exelon
suppress acetylcholinesterase and help maintain
acetylcholine levels that, in Alzheimer's patients,
steadily drop as brain cells die. The trouble is, the
results of clinical drug trials are often
over-interpreted, says Dr. Hanna Kaduszkiewicz, the
German paper's lead author and a physician at the
University Medical Centre Hamburg-Eppendorf, Hamburg's
largest hospital. "There are a lot of reasons for
this tendency," she says. "One of them
certainly is that doctors always want to be able to give
something to their patients, and therefore tend to be
more positive about innovations than they should
be."
The new doubts about the three drugs created a storm
of controversy, with scientists from around the world
challenging the German findings. However, it is
indisputable that only a small fraction of patients
respond positively to any of the three drugs, although
more exact percentages are not known. As well, the
response rate is so low, and the side effects so
potentially serious, that some clinicians are asking
whether these drugs ought to be prescribed at all. But
Dr. Jack Diamond, scientific director of the Alzheimer
Society of Canada, says such factors aren't reason
enough to get rid of the drugs. "What we want now
is not to say, 'Right, cholinesterase inhibitors don't
work, we don't want to use them,' " Diamond says.
"What should be done is more research to identify
the responders."
It seems unlikely that drug companies would line up
to do that kind of study, according to Dr. Thomas Perry,
a scientist at the Therapeutics Initiative, an
independent organization at the University of British
Columbia that assesses drug data. "Imagine, if
you're the drug company, if only one out of 10 patients
benefits," Perry says. "You'd cut your market
to 10 per cent of what it would otherwise have
been." Perry acknowledges it is possible the drugs
may work "for a few people," but in general,
he says, "I wouldn't expect much," other than
the common side effects, such as nausea, vomiting,
diarrhea, and weight loss. And, Perry adds, "our
analysis of all the experiments leads us to think that
about one in 50 people started on the drugs will have
something fairly nasty happen to them."
By nasty, Perry means a "serious adverse
event," defined as either death, hospitalization,
prolonged hospitalization or permanent disability. For
example, the three drugs can cause loss of bowel
control. "If that led to an older person lying in a
pool of their own feces for a few days," says
Perry, "their skin may break down, they may get an
infection, they may get hospitalized -- and some of them
die." So questionable is the value of these drugs
that British Columbia no longer pays for them. But
Diamond says anecdotal evidence suggests caregivers
coping with difficult patients find the drugs
invaluable. "Those small clinical changes are
enormously important to them," says Diamond.
"It makes a huge difference to their whole quality
of life." In the wake of the controversy, Perry has
some drug advice. "If you're going to try it, try
it very cautiously, and you and your family should be
aware of the adverse effects," he says. "Don't
just take it because the doctor said, 'I want you to try
this.' "
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