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Clozapine improves dyskinesias in Parkinson disease

A double-blind, placebo-controlled study

From the Department of Neurology, Hôpital Gabriel Montpied, Clermont–Ferrand, France.

Address correspondence and reprint requests to Dr. F. Durif, Department of Neurology, Hôpital Gabriel Montpied, BP 69-63003 Clermont–Ferrand, Cedex 1, France; e-mail: fdurif{at}chu-clermontferrand.fr

Objective: To investigate the efficacy and safety of clozapine in the treatment of levodopa-induced dyskinesias (LID) in patients with severe Parkinson disease (PD).

Methods: Fifty patients were randomized to treatment in this 10-week, double-blind, parallel-group, placebo-controlled, multicenter trial. The principal measure of outcome was the diurnal change in the "on" time with LID assessed using a self-evaluation of the motor performance fluctuations performed every 2 weeks. An acute levodopa challenge was also performed at the beginning and end of the study.

Results: A reduction in the duration of "on" periods with LID was noted in favor of the clozapine group at the end of the study (placebo group day 0: 4.54 ± 0.53 hours, end: 5.28 ± 0.70 hours; clozapine group day 0: 5.68 ± 0.66 hours, end: 3.98 ± 0.57 hours; p = 0.003). The mean clozapine dosage was 39.4 ± 4.5 (SEM) mg/day. The maximal LID score at rest during the levodopa challenge was significantly decreased under clozapine treatment, with a variation from day 0 to day 70 in the placebo group of +0.15 ± 1.01 and in the clozapine group of -2.22 ± 0.52 (p < 0.05). Five patients receiving clozapine and seven receiving placebo discontinued on account of adverse events. Among them, three patients in the clozapine group developed eosinophilia, which rapidly resolved after withdrawal of the drug.

Conclusion: Clozapine is effective in the treatment of levodopa-induced dyskinesias in severe PD.

Received April 11, 2003. Accepted in final form October 6, 2003.

See also page 349

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