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New Details in Schizophrenia Treatment Trial Emerge

Two new studies from the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) provide more insights into comparing treatment options, and to what extent antipsychotic medications help people with schizophrenia learn social, interpersonal and community living skills. The new studies are published in the March 2007 issue of the American Journal of Psychiatry. CATIE, a $42.6 million, multi-site study, was funded by the National Institutes of Health’s National Institute of Mental Health (NIMH).

Comparing Newer Antipsychotic Medications After Older One Fails
Quetiapine, and to some extent olanzapine, may be more effective than risperidone among patients who were originally taking, but had to discontinue, perphenazine — an older, first generation antipsychotic medication. However, patient responses varied considerably.

“CATIE continues to fine-tune our understanding of how our arsenal of antipsychotic medications work in real-world settings, but it also is revealing to us what questions we still must address,” said NIMH Director Thomas R. Insel, M.D.

Of the 257 patients who were initially randomized to perphenazine in the CATIE study, 192 discontinued the medication for various reasons, including ineffectiveness and intolerable side effects. Among those who discontinued, 114 agreed to be re-randomized to one of three newer antipsychotic medications — olanzapine, quetiapine or risperidone.

T. Scott Stroup, M.D., MPH, of the University of North Carolina at Chapel Hill, and colleagues compared the effectiveness of the medications by determining how long patients stayed on their assigned medication. Those taking quetiapine stayed on the longest — averaging about ten months before discontinuing. Those taking olanzapine discontinued after an average of about seven months, and those taking risperidone discontinued after an average of four months.

Although the discontinuation results suggest that olanzapine was generally on par with quetiapine, patients taking olanzapine experienced more side effects. While none of those taking quetiapine discontinued use due to weight gain or metabolic side effects, 13 percent of those assigned to olanzapine discontinued it due to weight gain or metabolic problems, and 5 percent of those on risperidone did so.

“These results reinforce the fact that finding the most effective medication for each patient sometimes means trying multiple medications,” said Dr. Stroup. “They remind us of the considerable variability in clinical circumstances and of our need to be responsive to an individual’s needs and preferences.”

Schizophrenia Patients’ Social and Community Living Skills Improve Modestly While on Antipsychotic Medications
Patients with schizophrenia taking antipsychotic medications experience modest improvements in social, interpersonal and community living (psychosocial) skills, regardless of what antipsychotic medication they are taking.

Improvements in psychosocial skills among patients with schizophrenia have been notoriously difficult to achieve, even when the more disruptive symptoms of the disease can be controlled. “Helping patients with schizophrenia restore their psychosocial functioning remains a challenge,” said NIMH Director Thomas R. Insel, M.D. “These CATIE results reinforce the growing understanding that we must do a better job of helping patients get their life skills back on track.”

Marvin Swartz, M.D., of Duke University and colleagues evaluated the social and vocational functioning, interpersonal relationships, and psychological well-being of 455 participants — about one-third of all patients in the CATIE study — who completed an initial evaluation before the study began and were available to provide data after 12 months of treatment. In the first phase of the CATIE study, patients were randomly assigned to take either perphenazine — an older, first-generation antipsychotic medication — or one of several newer, second-generation medications (olanzapine, quetiapine, risperidone, or ziprasidone).

The researchers found that those patients who stuck with their initial treatment showed some improvement in their psychosocial functioning, and there were no differences among the medications in making these gains. The results are consistent with previously reported CATIE results (http://www.nimh.nih.gov/healthinformation/catie.cfm) in which few differences were seen among perphenazine and the newer, second-generation antipsychotic medications in effectively reducing symptoms.

The patients who made the greatest gains were the ones with the poorest community living skills at the beginning of the study, but they were also more likely to discontinue treatment early in the process. As noted in previous CATIE reports, many patients discontinued their initial treatments because of intolerable side effects or ineffectiveness.

“Over the long run patients are more likely to function better in the community if they are able to stay on their initial treatment, especially those who are the most impaired,” said Dr. Swartz. “More intensive rehabilitative interventions and outreach may help patients stick with their treatment and make greater gains.”

Patients who made few gains in community living skills were those with higher-level psychosocial skills at the beginning of the study. Swartz and colleagues posit that patients encountered a “ceiling effect” at which point additional psychosocial skill improvement was unlikely without additional rehabilitative treatment.

“Overall, the findings reiterate the widely held belief that antipsychotic medications alone are not sufficient in helping patients make meaningful gains in real-world functioning,” said Dr. Swartz. “Dedicated rehabilitative services that help patients learn to function at work and in social settings are sorely needed.”

The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, http://www.nimh.nih.gov.

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 it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


Stroup TS, et al. Effectiveness of Olanzapine, Quetiapine and Risperidone in Patients with Chronic Schizophrenia After Discontinuing Perphenazine: A CATIE Study. American Journal of Psychiatry 2007; 164:3.

Swartz MS, et al. Effects of Antipsychotic Medications on Psychosocial Functioning in Patients with Chronic Schizophrenia: Findings From the NIMH CATIE Study. American Journal of Psychiatry 2007; 164:3.
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