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Low-Dose Clozapine for Drug-Induced Psychosis in PD Abstract Background: Drug-induced psychosis is a difficult problem to manage in patients with Parkinson's disease. Multiple open-label studies have reported that treatment with clozapine at low doses ameliorates psychosis without worsening parkinsonism. Methods: We conducted a randomized, double-blind, placebo-controlled trial of low doses of clozapine (6.25 to 50 mg per day) in 60 patients at six sites over a period of 14 months. The patients (mean age, 72 years) had idiopathic Parkinson's disease and drug-induced psychosis of at least four weeks' duration. All the patients continued to receive fixed doses of antiparkinsonian drugs during the four weeks of the trial. Blood counts were monitored weekly in all the patients. Results: The mean dose of clozapine was 24.7 mg per day. The patients in the clozapine group had significantly more improvement than those in the placebo group in all three of the measures used to determine the severity of psychosis. The mean (±SE) scores on the Clinical Global Impression Scale improved by 1.6±0.3 points for the patients receiving clozapine, as compared with 0.5±0.2 point for those receiving placebo (P<0.001). The score on the Brief Psychiatric Rating Scale improved by 9.3±1.5 points for the patients receiving clozapine, as compared with 2.6±1.3 points for those receiving placebo (P=0.002). The score on the Scale for the Assessment of Positive Symptoms improved by 11.8±2.0 points for the patients receiving clozapine, as compared with 3.8±1.9 points for those receiving placebo (P=0.01). Seven patients treated with clozapine had an improvement of at least three points on the seven-point Clinical Global Impression Scale, as compared with only one patient given placebo. Clozapine treatment improved tremor and had no deleterious effect on the severity of parkinsonism. In one patient, clozapine was discontinued because of leukopenia. Conclusions: Clozapine, at daily doses of 50 mg or less, is safe and significantly improves drug-induced psychosis without worsening parkinsonism. (N Engl J Med 1999;340:757-63.) Copyright 1999 by the Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine March 11, 1999 -- Vol. 340, No. 10 The Parkinson Study Group Appendix The following persons participated in the study: Investigators -- J. Friedman and M. Lannon, Memorial Hospital of Rhode Island, Pawtucket C. Comella, Rush-Presbyterian-St. Luke's Medical Center, Chicago; S. Factor, Albany College of Medicine, Albany, N.Y.; R. Kurlan and I. Richard, University of Rochester, Rochester, N.Y.; M. Parsa, Case Western University School of Medicine, Cleveland; R. Pfeiffer, University of Tennessee Medical Center, Memphis; Study Coordinators -- R. Davies, Memorial Hospital of Rhode Island, Pawtucket K. Janko, Rush-Presbyterian-St. Luke's Medical Center, Chicago; D. Brown, Albany College of Medicine, Albany, N.Y.; I. Gardner and N. Pearson, University of Rochester, Rochester, N.Y.; K. Large, Case Western University School of Medicine, Cleveland; S. Rast, University of Tennessee Medical Center, Memphis; Steering Committee -- D. Oakes, University of Rochester, Rochester, N.Y.; C. Goetz, Rush-Presbyterian-St. Luke's Medical Center, Chicago; G. Paulson, Ohio State University, Columbus; F. Marshall, K. Kieburtz, and A. Rudolph, University of Rochester, Rochester, N.Y.; Clinical Trials Coordination Center -- K. Bourgeois, C. Casacelli, A. Freimuth, B. Guthrie, R. Pelusio, and A. Watts, University of Rochester, Rochester, N.Y.; Safety Monitoring Committee -- P. Tariot and R. Raubertas, University of Rochester, Rochester, N.Y.; and T. Greenamyre, Emory University, Atlanta. janet paterson - 51 now /41 dx /37 onset - almonte/ontario/canada <http://www.newcountry.nu/pd/members/janet/index.htm> [log in to unmask]