Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease

Background Drug-induced psychosis is a difficult problem to manage in patie nts with Parkinson's disease. Multiple open-label studies have reported tha t treatment with clozapine at low doses ameliorates psychosis without worse ning parkinsonism. Methods We conducted a randomized, double-blind, placebo-controlled trial o f low doses of clozapine (6.25 to 50 mg per day) in 60 patients at six site s over a period of 14 months. The patients (mean age, 72 years) had idiopat hic Parkinson's disease and drug-induced psychosis of at least four weeks' duration. All the patients continued to receive fixed doses of antiparkinso nian 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 place bo group in all three of the measures used to determine the severity of psy chosis. The mean (+/-SE) scores on the Clinical Global Impression Scale imp roved 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 t he Brief Psychiatric Rating Scale improved by 9.3+/-1.5 points for the pati ents receiving clozapine, as compared with 2.6+/-1.3 points for those recei ving placebo (P=0.002). The score on the Scale for the Assessment of Positi ve Symptoms improved by 11.8+/-2.0 points for the patients receiving clozap ine, 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 thre e points on the seven-point Clinical Global Impression Scale, as compared w ith 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 signifi cantly improves drug-induced psychosis without worsening parkinsonism. (N E ngl J Med 1999;340:757-63.) (C)1999, Massachusetts Medical Society.