The Clinical Antipsychotic Trials of Intervention Effectiveness project (CATIE) is a new 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
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
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.
Schizophrenia Trial is a randomized controlled trial that will evaluate
the effectiveness of atypical and conventional antipsychotic medications
in patients with schizophrenia over an 18 month period.
- To determine
the long-term effectiveness and tolerability (all-cause treatment discontinuation)
of the newer atypical antipsychotics, relative to each other.This will
involve contrasting treatment with olanzapine vs. treatment with quetiapine
vs. treatment with risperidone vs. treatment with ziprasidone.
- To determine
the long-term effectiveness and tolerability of the newer atypical antipsychotics
relative to a conventional antipsychotic (perphenazine). This will involve
contrasting the oral conventional antipsychotic group with the combined
newer atypical antipsychotic groups.
- To determine,
among patients who fail treatment with an initially assigned newer atypical
antipsychotic due to lack of efficacy, the long-term effectiveness and
tolerability of the other newer atypical antipsychotics, relative to
- To determine,
among patients who discontinue treatment with an initially assigned
newer atypical antipsychotic due to treatment intolerance, the long-term
effectiveness and tolerability of the other newer atypical antipsychotics,
relative to ziprasidone.
The AD trial
is a randomized, parallel group, double-blinded study comparing treatment
with olanzapine, quetiapine, risperidone, and placebo in AD patients with
delusions or hallucinations AND/OR clinically significant aggression or
- To compare
the acute efficacy and effectiveness of risperidone, olanzapine, and
quetiapine in treatment algorithms over the course of 36 weeks in treating
psychosis in outpatients with Alzheimer's disease
- To assess
their relative effectiveness at maintaining clinical improvement up
to 36 weeks.