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Clozapine

A 2-year open trial in Parkinson's disease patients with psychosis

Department of Neurology, Albany Medical College, Albany, NY.

We treated 17 patients with Parkinson's disease (PD) complicated by psychosis with the atypical antipsychotic drug, clozapine, for 6 to 24 months (mean, 15 months) in a prospective, open-label trial. At 3-month intervals we evaluated patients, using a simplified brief Psychiatric Rating Scale (PRS), the motor examination portion of the Unified Parkinson's Disease Rating Scale, and the Mini-Mental State Examination (MMSE). Mean PRS score was significantly improved when compared with baseline over 1 year (p < 0.01) and nonsignificantly improved for the second year. We maintained the levodopa dose at levels that were 17 to 68% higher than baseline, and the mean motor examination score improved by 11 to 22% in the first 15 months. Clozapine dosage utilized in the trial ranged from 6.25 mg every other day to 150 mg/d. Adverse effects, including sedation and confusion, were common. These results demonstrate that clozapine therapy can be effective in treating psychosis in PD patients over 1 to 2 years. The decline in efficacy in the second year was most likely related to an increase in daily levodopa dose, progression of dementia (illustrated by a decline in MMSE score), and an inability of PD patients to tolerate higher doses of clozapine.

Address correspondence and reprint requests to Dr. Stewart A. Factor, Albany Medical College, Department of Neurology (A70), Albany, NY 12208.

Supported by a grant from Sandoz Pharmaceuticals Corporation and the Albany Medical College Parkinson's Research Fund.

Presented in part at the 45th annual meeting of the American Academy of Neurology, New York, NY, April 29, 1993.

Received June 10, 1993. Accepted for publication in final form September 16, 1993.