New CATIE Analyses Offer Guidance for Choosing Second-Generation Antipsychotic Medication
Mar 7, 2007 - 3:19:41 PM

For patients with chronic schizophrenia who switched from perphenazine to a second-generation antipsychotic, quetiapine and olanzapine were more effective than risperidone. Perphenazine, a first-generation antipsychotic drug, showed effects comparable to most newer drugs in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, but many patients eventually switched because of problems with limited effectiveness or poor tolerability. An analysis of what happens to these patients is presented in the March issue of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association (APA).

The findings are reported by T. Scott Stroup, M.D., M.P.H., Department of Psychiatry, University of North Carolina, in the AJP article, “Effectiveness of Olanzapine, Quetiapine, and Risperidone in Patients With Chronic Schizophrenia After Discontinuing Perphenazine: A CATIE Study.” The 114 patients had discontinued perphenazine in phase one of the study and were then randomly assigned to a second-generation antipsychotic in phase one B. Assessments were conducted every three months over 18 months.

The mean time to discontinuation for the second-generation drug was 10 months for quetiapine, seven months for olanzapine and four months for risperidone. However, the three treatment groups did not differ in the time to discontinuation specifically due to lack of efficacy or tolerability. The only adverse medical events for which rates differed among groups were weight gain and increases in total cholesterol and triglyceride levels which were greatest for olanzapine. A weight gain of more than seven percent of baseline body weight occurred in 36 percent of the patients taking olanzapine, 24 percent of the quetiapine group and 14 percent of the risperidone group.

Inability to tolerate the medication was examined within the 37 patients who had stopped taking perphenazine because of intolerability. None discontinued quetiapine for this reason, whereas 64 percent of the olanzapine group and 69 percent of the risperidone group discontinued treatment because of adverse effects. The outcomes for the three second-generation antipsychotics are somewhat different from those in CATIE phase one and phase two. All participants discontinued perphenazine immediately before entering this study and appeared to respond best to the study medications that differ from perphenazine most significantly (olanzapine and quetiapine) and responded less well to the more similar drug risperidone.

“In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances,” stated AJP Editor in Chief Robert Freedman, M.D. “This study guides clinicians to a second choice if patients need to be switched to another drug.” An editorial by Stephen Marder, M.D., UCLA, points out that subtle problems with movement disorders, a known side effect of the first-generation drug, lead to their limited usefulness in some patients.

“The editorial by Marder points to the often subtle clinical experience of neurological side effects from antipsychotic medications that induced patients to discontinue these treatments in the CATIE study,” said Darrel A. Regier, M.D., M.P.H., director of the APA’s Division of Research. “By understanding patient vulnerabilities and known side effects of specific medications, clinicians have the potential for greater tailoring of treatment plans for individual patients when the full range of medications is available on formularies.”

In a companion AJP article, “Effects of Antipsychotic Medications on Psychosocial Functioning in Patients With Chronic Schizophrenia: Findings From the NIMH CATIE Study,” Marvin Swartz, M.D., Duke University, evaluated the social and vocational functioning, interpersonal relationships and psychological well-being of 455 participants who completed an initial evaluation before the study began and were available to provide data after 12 months of treatment. They found that patients with schizophrenia taking antipsychotic medications experience modest improvements in social, interpersonal and community living skills, regardless of what antipsychotic medication they are taking.

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. Patients who made few gains in community living skills were those with higher-level psychosocial skills at the beginning of the study, which the authors posit as being a “ceiling effect” at which point additional psychosocial skill improvement was unlikely without additional rehabilitative treatment.

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