The approval of chlorpromazine
for schizophrenia in 1954 played a crucial role in the
disappearance of the old-style asylum and allowed thousands
of patients to function in society and at home. But
the antipsychotic drugs that followed have always traded
efficacy against some pretty daunting side effects —
and the latest evidence suggests the situation is little
better today.
NEWER
DOESN'T MEAN BETTER
The newest generation of antipsychotics — dubbed
atypical because they were believed to eliminate side
effects like parkinsonism and dyskinesias which plagued
older typical agents — have come under fire in
recent weeks after two studies demonstrated they are
in fact just as problematic.
The first, conducted by the Institute
for Clinical Evaluative Sciences (ICES) and published
in the September 12 issue of the Archives of Internal
Medicine, tracked over 57,000 Ontarians aged 66
years and older. Researchers found that the risk of
parkinsonism in patients dispensed high-dose atypical
antipsychotics for dementia was actually comparable
to those dispensed typical agents. "These results are
really concerning when you consider that previous ICES
research has shown that atypical antipsychotics make
up over 80% of the antipsychotics prescribed in Ontario,"
Dr Paula Rochon, study lead author and ICES scientist,
stated in a press release.
Unfortunately, the bad news doesn't
end there. A second study, supported by the US National
Institute of Mental Health, has reviewed four of the
atypical antipsychotics and found them little more effective
than the last generation — despite costing about
ten times more. The double-blind study, published online
September 19 in the NEJM, followed 1,493 American
patients taking one of five drugs: the off-patent perphenazine,
and the atypical antipsychotics olanzapine, quetiapine,
risperidone and ziprasidone.
The researchers found all these
treatments were plagued by poor compliance and low patient
satisfaction. By the end of the 18-month study, an astonishing
74% of the patients had stopped taking the drug they
had been assigned. What's worse, results showed that
the newer treatments were accompanied by even more insidious
metabolic problems including severe weight gain, often
accompanied by type II diabetes and high cholesterol.
Commenting on these findings in
an accompanying editorial, Dr Robert Freedman, MD, of
the University of Colorado is hardly overstating the
case when he opines: "The results could be viewed as
discouraging."
THE
LEAST OF ALL EVILS
Schizophrenia affects roughly 1% of the Canadian population.
Of the four atypical antipsychotics included in the
NEJM study, quetiapine is the most recent arrival
in the country, while ziprasidone is expecting imminent
approval.
Clozapine, the original atypical
antipsychotic, is quite widely used in Canada but wasn't
included in the comparative study because its superior
efficacy has been well established. Clozapine doesn't
cause movement disorders, but it is more toxic, carrying
a risk of agranulocytosis not seen with later drugs.
"The patient with schizophrenia
and his or her doctor face difficult choices," comments
Dr Freedman. "Two drugs, olanzapine and clozapine, appear
to be more effective than other agents. However, both
drugs induce a significantly greater number of serious
side effects."
Difficult choices indeed —
but there may be light at the end of the tunnel. The
next generation of antipsychotics now in development
target a quite different mechanism than the atypicals.
So at the least we can expect them to bring a quite
different set of problems.
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