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NIMH Study To Guide Treatment Choices for Schizophrenia (Phase 1 Results)

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Press Release

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 2.4 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 $42.6 million 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 2.4 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.

More information on CATIE

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About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): 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. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website .