CATIE study to guide schizophrenia treatment
Sep 20, 2005, 21:47, Reviewed by: Dr.
|CATIE greatly enhances the knowledge available to guide treatment choices for people with schizophrenia. CATIE provides new information on the efficacy and side effects of antipsychotic drugs, compared head to head, helping doctors determine the appropriateness of specific medications in individual patients. The combination of maximizing the benefits while minimizing the side effects increases the likelihood that a person with schizophrenia will stay on their antipsychotic medication, a necessary ingredient for managing symptoms and reducing the risk of relapse.
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. 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 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. 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.
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. 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.
The aim of the CATIE study was to determine which medications provide the best treatment for schizophrenia. Many studies have tested new antipsychotic medications in schizophrenia. By contrast, CATIE compared four of the newer medications to one another, and to an older medication.
For the first time, doctors and people with schizophrenia will have extensive information on antipsychotic medications from a single, large, long-term study directly comparing the drugs to each other.
CATIE greatly enhances the knowledge available to guide treatment choices for people with schizophrenia. CATIE provides new information on the efficacy and side effects of antipsychotic drugs, compared head to head, helping doctors determine the appropriateness of specific medications in individual patients.
All medications included in the study were FDA-approved antipsychotic medications used in the treatment of schizophrenia. Patients were randomly assigned to a medication; study participants and their doctors could not choose which medication to take, and neither the investigators nor the patients knew which antipsychotic a patient was on.
For patients with schizophrenia, staying on medication is critical to controlling symptoms and preventing relapse. Previous studies have shown that antipsychotic treatment is far better than no treatment. Investigators also recorded why a patient stopped a medication: if the medication did not control symptoms, or if the side effects were not tolerable, or if the patient chose to stop treatment for some other reason. Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications.
The study supplies important new information that will help doctors and patients choose the most appropriate medication according to the patients' individual needs.
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. Perphenazine (the older medication) equally as effective as the other three newer medications (risperidone, quetiapine, and ziprasidone) and was as well tolerated as the newer drugs. Patients and doctors must carefully evaluate the trade off between effectiveness, side effects, and cost in choosing an appropriate medication.
The pharmaceutical companies donated the study medications and provided advice about the optimal dose for that company's medication.
- The study results are published in the September 22 issue of the New England Journal of Medicine.
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.
1. Lieberman, J.A. and Stroup, T.S. (2003). Guest editor's introduction: what can large pragmatic clinical trials do for public mental health care. Schizophrenia Bulletin, (29) 1, p. 1-6.
2. Stroup, T. S., McEvoy, J.P., Swartz, M.S., Byerly, M.J., Glick, I.D., Canive, J.M., McGee, M.F., Simpson, G.M., Stevens, M.C., Lieberman, J.A. (2003). The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project: schizophrenia trial design and protocol development. Schizophrenia Bulletin, (29) 1, p. 15-31.
3. Lieberman, J.A., Stroup, T.S., McEvoy, J.P., Swartz, M.S., Rosenheck, R.A., Perkins, D.O., Keefe, R.S.E., Davis, S.M., Davis, C.E., Lebowitz, B.D., Severe, J., Hsiao, J.K. (2005). Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. New England Journal of Medicine, (353), p.1209 -1223.
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