|NIMH Study to Guide Treatment Choices for Schizophrenia
A large study funded by NIH’s National Institute of Mental Health
(NIMH) provides, for the first time, detailed information comparing
the effectiveness and side effects of five medications — both new
and older medications — that are currently used to treat people
with schizophrenia. Overall, the medications were comparably effective
but were associated with high rates of discontinuation due to intolerable
side effects or failure to adequately control symptoms. One new
medication, olanzapine, was slightly better than the other drugs
but also was associated with significant weight-gain and metabolic
changes. Surprisingly, the older, less expensive medication used
in the study generally performed as well as the newer medications.
The study, which included more than 1,400 people, supplies important
new information that will help doctors and patients choose the
most appropriate medication according to the patients’ individual
needs. The study results are published in the September 22 issue
of the New England Journal of Medicine.
“The study has vital public health implications because it provides
doctors and patients with much-needed information comparing medication
treatment options,” said NIMH Director Thomas R. Insel, M.D. “It
is the largest, longest, and most comprehensive independent trial
ever done to examine existing therapies for this disease.”
Schizophrenia, which affects 3.2 million Americans, is a chronic,
recurrent mental illness, characterized by hallucinations, delusions,
and disordered thinking. The medications used to treat the disorder
are called antipsychotics. Previous studies have demonstrated that
taking antipsychotic medication is far more effective than taking
no medicine, and that taking it consistently is essential to the
long-term treatment of this severe, disabling disorder. Although
the medications alone are not sufficient to cure the disease, they
are necessary to manage it.
In the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)
trial, researchers directly compared an older medication (perphenazine),
available since the 1950s, to four newer medications (olanzapine,
quetiapine, risperidone, and ziprasidone), introduced in the 1990s.
The purpose of the study was to learn whether there are differences
among the newer medications and whether the newer medications hold
significant advantages over the older medications; these newer
medications known as atypical antipsychotics, cost roughly 10 times
as much as the older medications.
The size and scope of the trial, with more than 1,400 participants
at 57 sites around the country, its 18-month duration, and its
inclusion of a wide range of patients in a variety of treatment
settings ensure that the findings are reliable and relevant to
the 3.2 million Americans suffering from schizophrenia.
At the beginning of the study, patients were randomly assigned
to receive one of the five medications. Almost three quarters of
patients switched from their first medication to a different medication.
The patients started on olanzapine were less likely to be hospitalized
for a psychotic relapse and tended to stay on the medication longer
than patients taking other medications. However, patients on olanzapine
also experienced substantially more weight gain and metabolic changes
associated with an increased risk of diabetes than those study
participants taking the other drugs.
Contrary to expectations, movement side effects (rigidity, stiff
movements, tremor, and muscle restlessness) primarily associated
with the older medications, were not seen more frequently with
perphenazine (the drug used to represent the class of older medications)
than with the newer drugs. The older medication was as well tolerated
as the newer drugs and was equally effective as three of the newer
medications. The advantages of olanzapine — in symptom reduction
and duration of treatment — over the older medication were modest
and must be weighed against the increased side effects of olanzapine.
Thus, taken as a whole, the newer medications have no substantial
advantage over the older medication used in this study. An important
issue still to be considered is individual differences in patient
response to these drugs.
Several factors, such as adequacy of symptom relief, tolerability
of side effects, and treatment cost influence a person’s willingness
and ability to stay on medication.
“There is considerable variation in the therapeutic and side effects
of antipsychotic medications. Doctors and patients must carefully
evaluate the tradeoffs between efficacy and side effects in choosing
an appropriate medication. What works for one person may not work
for another,” said Jeffrey Lieberman, M.D., CATIE’s Principal Investigator
and Chair of The Department of Psychiatry, Columbia University
and Director of the New York State Psychiatric Institute.
The CATIE study was led by Lieberman, and co-Principal Investigators
Scott Stroup, M.D. (University of North Carolina at Chapel Hill),
and Joseph McEvoy, M.D. (Duke University). CATIE was carried out
by researchers at 57 sites across the country, including private
and public mental health clinics, Veteran’s Health Administration
Medical Centers, and University Medical Centers, where people with
schizophrenia received their usual care.
This New England Journal of Medicine article is the first to report
outcomes from the CATIE schizophrenia trial, and addresses many
of the primary questions from the study. Future reports will address
a multitude of topics (e.g., cost-effectiveness of the medications,
quality of life, predictors of response) and will provide a more
detailed picture of the interaction between patient characteristics,
medication, and outcomes. The information from the CATIE study
will inform new approaches for improving outcomes in schizophrenia.
CATIE is part of an overall NIMH effort to conduct “practical” clinical
trials that address public health issues important to those persons
affected by major mental illnesses in real world settings.
The NIMH mission is to reduce the burden of mental illness and
behavioral disorders through research on mind, brain, and behavior.
Additional information about NIMH and schizophrenia can be found
at its website, www.nimh.nih.gov.
NIMH is part of the National Institutes of Health (NIH), the Federal
Government's primary agency for biomedical and behavioral research.
NIH is a component of the U.S. Department of Health and Human Services.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U. S. Department of Health
and Human Services. It is the primary Federal agency for conducting
and supporting basic, clinical, and translational medical research,
and investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs,