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Patient recruitment for the CATIE Alzheimer's Disease Study will end on December 31st, 2003.
The Clinical Antipsychotic Trials of Intervention Effectiveness project
(CATIE) is a research project to evaluate the clinical effectiveness of
atypical antipsychotics in the treatment of schizophrenia and Alzheimer's
disease.
The introduction of antipsychotic drugs in the 1950s heralded the "golden
age" of psychopharmacology. Their development compares to the discovery
of antibiotics for infectious diseases. Conventional antipsychotic drugs,
typified by chlorpromazine and haloperidol, have a proven track record
in the treatment of schizophrenia. However, almost a half century of experience
has revealed their substantial limitations. They are most effective against
the psychotic symptoms of the illness and in its early stages, but their
side effects are troubling and contribute significantly to non-compliance,
which leads to relapse and rehospitalization. They also do not alleviate
all the symptoms and disability caused by the illness, and substantial
proportions of these patients continue to be severely disabled and relapse
frequently, and require hospitalization.
Although they were first developed for schizophrenia, antipsychotic drugs
are now broadly used for other disorders, including behavioral signs and
symptoms associated with Alzheimer's disease and other dementias. Despite
their widespread use in these conditions, the overall effectiveness and
safety of these drugs remain unclear.
The advent of atypical antipsychotic drugs, with their potential for
enhanced efficacy and safety, has changed the risk/benefit profile of
this drug class. Following the introduction of the first atypical antipsychotic,
clozapine, in 1990, several new atypical drugs have become available for
clinical use and have now acquired more than 50% of the antipsychotic
drug market in the United States. These drugs include risperidone (1994),
olanzapine (1996) and quetiapine (1997).
Recent research has provided strong evidence of the efficacy of atypicals
in schizophrenia, and demonstrated that they greatly reduce the risk of
extrapyramidal side effects. There is a growing belief among clinicians
that they are or should become first-line treatments in schizophrenia.
However, the exact nature and extent of the clinical advantages of the
atypical drugs are not known. Moreover, they cost more than ten times
as much as most older drugs. And although a variety of claims of efficacy
and safety have been made, they are often based on insufficient evidence.
Among the reasons for this is the fact that traditional clinical trials
have excluded many patients with schizophrenia, including those who are
substance abusers, violent or uncooperative, thus making it difficult
to generalize the results of such studies to real world patients. For
reasons of external validity, treatment effectiveness studies have sought
to use more representative sampling techniques. However, even effectiveness
studies rarely have representative samples of providers and systems of
care or large enough samples to have sufficient power to examine the role
of external factors affecting treatment outcome.
In recent years clinical psychopharmacology research has been dominated
by the pharmaceutical industry. While industry-sponsored research is critical
to new product development, its emphasis is on meeting regulatory and
marketing requirements and on obtaining expanded marketing claims for
the drug. not on evaluating the effectiveness of the product at the general
population level. As a result, industry-sponsored research does not address
broad public health needs or the needs of individual practitioners seeking
to make good clinical decisions for individual patients.
Research within a broad public-health perspective is needed, addressing
the needs of patients in general, in which exclusion criteria are minimal,
outcomes are construed broadly, a wide range of treatment settings are
included, and sample sizes are large enough to assure adequate power.  |
