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April 1, 2006 -- No. 177
Many schizophrenia patients benefit by switching
to second medication, UNC-led study finds
CHAPEL HILL -- Many schizophrenia patients who donít respond well to their first antipsychotic medication see improvement after switching to a second medication, the second round of a landmark University of North Carolina at Chapel Hill-led study has found.
These results, from phase 2 of the Clinical Antipsychotic Trials of Intervention Effectiveness, are reported in two separate articles published in the April issue of the American Journal of Psychiatry. The $60 million CATIE trial began in 1999 and is run by the UNC School of Medicineís department of psychiatry, with funding from the National Institute of Mental Health.
"Phase 2 of CATIE shows that although all the drugs used to treat schizophrenia have some limitations, people who donít do well on one drug can do well on another drug," said Dr. Scott Stroup, an associate professor at UNC and lead author of one of the articles. The lead author of the other article is Dr. Joseph McEvoy, associate professor of biological psychiatry at Duke University Medical Center.
"If a patient didnít do well on a drug for a particular reason, phase 2 of CATIE provides information on what drug to choose next," Stroup added.
Specifically, patients experiencing continued symptoms such as hallucinations or delusions on one antipsychotic drug might see a reduction in these symptoms if they switch to clozapine (brand name: Clozaril) or olanzapine (Zyprexa). Patients who stop a drug because of metabolic side effects, such as weight gain or elevated cholesterol levels, might benefit from switching to risperidone (Risperdal) or ziprasidone (Geodon), Stroup said.
Dr. Robert Freedman, editor of the American Journal of Psychiatry, said the CATIE results "are the largest, most comprehensive set of data available on the pharmacological treatment of schizophrenia. As intended, their results provide guidance to doctors, patients and families on a logical sequence of treatments with significant information on the probability of therapeutic response and the severity of side effects at each phase."
Results from phase 1 of CATIE were reported in September in the New England Journal of Medicine. In phase 1, the researchers found that perphenazine, a first-generation antipsychotic medication used since the 1950s to treat people with schizophrenia, works about as well as four newer, more expensive drugs introduced in the 1990s. They also found that one of the second-generation or "atypical" antipsychotic medications, olanzapine (Zyprexa), was slightly better than the other drugs but was associated with significant weight gain as a side effect.
More than 70 percent of patients discontinued their first drug before the end of the 18-month first phase because of inadequate effectiveness in controlling their symptoms, intolerable side effects or their own decision not to continue.
In the second phase, 543 patients were assigned to a newer drug that they had not taken during the first phase. Of these patients, 99 agreed to try to clozapine, a second-generation drug known to be more effective than other drugs in patients with treatment-resistant schizophrenia, but also with increased side effects; 49 actually received clozapine and 50 were assigned to other drugs for comparison. Patients taking clozapine had the longest median treatment duration (10.5 months). Clozapine had a lower discontinuation rate (56 percent) than the other atypical antipsychotics to which it was compared (their discontinuation rates ranged from 71 percent to 93 percent).
In the study involving the other 444 patients who continued to phase 2 of the study, the rates of treatment discontinuation were between 64 percent and 84 percent, but patients taking olanzapine and risperidone stayed on the medication for longer periods of time (6.3 and 7.0 months, respectively) than patients taking quetiapine (Seroquel) and ziprasidone (4.0 and 2.8 months). Olanzapine appeared to be the best of these drugs at reducing symptoms, while risperidone was the best tolerated.
Phase 2 reaffirms clozapineís superior effectiveness for treatment-resistant schizophrenia, Stroup said. Among the other atypical antipsychotics, olanzapine had advantages in several comparisons of treatment effectiveness in phases 1 and 2. Risks of substantial weight gain and high cholesterol and triglyceride levels occur in many patients who receive either olanzapine or clozapine. Clozapine is generally not the first choice for schizophrenia treatment, despite its greater effectiveness, because it increases the risk for agranulocytosis, a serious blood disorder in which the patient can no longer produce white blood cells. Agranulocytosis developed in one of the 49 patients.
In clinical practice, patients in whom the antipsychotic drugs fail are often hospitalized and re-treated with the same or a different drug. Although all of the drugs are approved for use in the United States by the U.S. Food and Drug Administration (FDA) after studies showing their safety and effectiveness, how patients should be subsequently treated when one drug fails and how the drugs compare to each other had not been well established prior to the CATIE study, Stroup said.
The CATIE effectiveness trials include a wide range of patients, a variety of health-care settings and a broad range of clinically meaningful outcome measures, he added.
More than 1,400 patients took part in the CATIE trials at 57 sites nationwide. CATIE sites in North Carolina included UNC, Duke University Medical Center, John Umstead Hospital in Butner, Dorothea Dix Hospital in Raleigh and the Behavioral Health Center in Charlotte. Quintiles Transnational, based in Research Triangle Park, provided extensive logistical support for the nationwide study.
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UNC School of Medicine contact: Stephanie Crayton, (919) 966-2860 or firstname.lastname@example.org