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Previous Volume 340:757-763 March 11, 1999 Number 10 Next

	Full Text PDF Editorial by Cummings, J. L. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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.

Source Information

Address reprint requests to Dr. Joseph H. Friedman at the Memorial Hospital of Rhode Island, 111 Brewster St., Pawtucket, RI 02860, or at joseph_friedman{at}mhri.org. Dr. Friedman assumes responsibility for the overall content and integrity of the manuscript.

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