• Science Update
A national clinical trial comparing clozapine with other new-generation antipsychotic medications for the treatment of chronic schizophrenia has shown that people who switched to clozapine from their first medication because it failed to manage symptoms adequately were twice as likely to continue treatment as patients who switched to other antipsychotic medications. A companion study found that for people who switched to new-generation antipsychotic medications other than clozapine, those who took olanzapine and risperidone continued taking their medication longer than people taking quetiapine and ziprasadone. The results of the trial, which was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, were published in two papers in the April 2006 issue of the American Journal of Psychiatry.
The results of CATIE — Clinical Antipsychotic Trials of Intervention Effectiveness — offer the 2.4 million adults in the United States with chronic schizophrenia and their doctors information that can help tailor treatments to the individual needs of patients. In phase 2 of this study, 543 people were studied in 57 different treatment sites to provide guidance to help doctors determine what to do next when patients need to change medications, a common occurrence in treating schizophrenia. Research has shown that patients who consistently receive treatment do much better than those who stop taking their medications, so finding the right treatment is crucial.
The lead investigators for the two studies in phase 2 of CATIE were Jeffrey A. Lieberman, M.D., of Columbia University and the New York State Psychiatric Institute; Scott Stroup, M.D., of the University of North Carolina at Chapel Hill; and Joseph McEvoy, M.D., of Duke University. These studies were the next step for patients who did not do well on their first medication in phase 1 of the trial, results of which were published in the New England Journal of Medicine in September 2005.
Phase 2 of CATIE compared the medications, called "atypical antipsychotics," with each other in two different groups of participants. In one group, patients who had stopped taking a phase 1 medication because symptoms were not adequately relieved were randomly assigned to get one of four medications: clozapine, olanzapine, quetiapine, or risperidone. In that group, clozapine was the most effective. Forty-four percent of the patients who changed to clozapine stayed on it for the rest of the 18-month study, compared with 18 percent of patients who had changed to the other medications. On average, patients stayed on clozapine for 10 months, while patients on any of the other medications stayed on them for only 3 months.
However, not all patients can or want to take clozapine, because it may cause serious side effects in some people, including inflammation of the heart muscle, and agranulocytosis, which is a dangerous drop in levels of white blood cells that are part of the immune system. As a result, patients taking clozapine require close monitoring. Although the patients who took clozapine in this study tolerated it fairly well overall, one person developed agranulocytosis.
There were other phase 1 patients who had stopped taking their medication because of side effects or because they told their doctors they wanted to change medications. These patients, as well as patients who wanted more symptom relief but didn't want to take clozapine, took part in a different phase 2 medication trial. In this part of the trial, clozapine was not included, and ziprasidone, the newest of the atypical medications available in the early stages of CATIE, was compared with the other three (olanzapine, quetiapine, or risperidone). Ziprasidone is known to have very different side effects, and it does not usually cause weight gain, as the other medications do.
Overall, patients in this phase 2 group stayed on risperidone seven months and on olanzapine just over six months, compared to four months on quetiapine and less than three months on ziprasidone. Until phase 2 was completed, neither patients nor researchers knew which medications were given, unless it was clozapine, because of the need for close monitoring. None of the patients were given a placebo — "blank" pill — for comparison.
Future CATIE reports will address a number of topics, such as cost-effectiveness, quality of life, and predictors of response, and will provide a more detailed picture of the interaction between patient characteristics, medications, and outcomes. CATIE is part of an overall NIMH effort to conduct "practical" clinical trials that address public health issues important to people affected by major mental illnesses in real-world settings.
Other study authors from phase 2 include:
- Sonia M. Davis, M.D., Dr.PH, University of North Carolina
- Herbert Y. Meltzer, M.D., Vanderbilt University Medical Center
- Robert A. Rosenheck, M.D., Yale University
- Marvin S. Swartz, M.D., Duke University
- Diana O. Perkins, M.D., M.P.H., University of North Carolina
- Richard S. E. Keefe, Ph.D., Duke University
- Clarence E. Davis, Ph.D., University of North Carolina
- Joanne Severe, M.S., National Institute of Mental Health
- John K. Hsiao, M.D., National Institute or Mental Health
For more information on CATIE phase 2, visit:
For more information on CATIE phase 1, visit:
For general information on CATIE, visit: