Clozapine Alone versus Clozapine and Risperidone with Refractory Schizophrenia
William G. Honer, M.D., Allen E. Thornton, Ph.D., Eric Y.H. Chen, M.D., Raymond C.K. Chan, Ph.D., Jessica O.Y. Wong, M.B., Andrea Bergmann, M.D., Peter Falkai, M.D., Edith Pomarol-Clotet, M.D., Peter J. McKenna, M.B., Emmanuel Stip, M.D., Richard Williams, M.B., G. William MacEwan, M.D., Kishor Wasan, Ph.D., Ric Procyshyn, Ph.D., for the Clozapine and Risperidone Enhancement (CARE) Study Group
Background The treatment of schizophrenia with multiple antipsychoticdrugs is common, but the benefits and risks are not known.
Methods In a randomized, double-blind study, we evaluated patientswith schizophrenia and a poor response to treatment with clozapine.The patients continued to take clozapine and were randomly assignedto receive eight weeks of daily augmentation with 3 mg of risperidoneor with placebo. This course of treatment was followed by anoptional 18 weeks of augmentation with risperidone. The primaryoutcome was reduction in the total score for severity of symptomson the Positive and Negative Syndrome Scale (PANSS). The secondaryoutcomes included cognitive functioning.
Results A total of 68 patients were randomly assigned to treatment.In the double-blind phase, the mean total score for the severityof symptoms decreased from baseline to eight weeks in both therisperidone and the placebo groups. There was no statisticallysignificant difference in symptomatic benefit between augmentationwith risperidone and placebo: 9 of 34 patients receiving placeboand 6 of 34 receiving risperidone responded to treatment (P=0.38).The mean difference in the change in PANSS scores from baselineto eight weeks between those receiving risperidone and thosereceiving placebo was 0.1 (95 percent confidence interval, 7.3to 7.0). The verbal working-memory index showed a small declinein the risperidone group and a small improvement in the placebogroup (P=0.02 for the comparison between the two groups in thechange from baseline). The increase in fasting blood glucoselevels was mildly greater in the risperidone group than in theplacebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10mmol per liter], P=0.04). The incidence and severity of otherside effects did not differ between the two groups.
Conclusions In this short-term study, the addition of risperidoneto clozapine did not improve symptoms in patients with severeschizophrenia. (ClinicalTrials.gov number, NCT00272584
[ClinicalTrials.gov]
)
Source Information
From the Department of Psychiatry (W.G.H., R.W., G.W.M.) and the Division of Pharmaceutics and Biopharmaceutics (K.W.), University of British Columbia, Vancouver, Canada; Department of Psychology, Simon Fraser University, Burnaby, B.C., Canada (A.E.T.); Department of Psychiatry, University of Hong Kong, Hong Kong, China (E.Y.H.C.); Department of Psychology, Sun Yat-Sen University, Guangzhou, China (R.C.K.C.); Castle Peak Hospital, Hong Kong, China (J.O.Y.W.); Department of Psychiatry, Saarland University, Homburg, Germany (A.B., P.F.), Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom (E.P.-C., P.J.M.); Department of Psychiatry, University of Montreal, Montreal (E.S.); and Riverview Hospital, Port Coquitlam, B.C., Canada (R.P.).
Address reprint requests to Dr. Honer at the Centre for Complex Disorders and the Department of Psychiatry, University of British Columbia, Vancouver General Hospital Research Pavilion, 828 W. 10th Ave., Suite 211, Vancouver, BC V5Z 1L8, Canada, or at honer{at}interchange.ubc.ca.
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