Clozapine Effective in Drug-Induced Psychosis in Parkinson's Disease

Laurie Barclay, MD

May 14, 2004

May 14, 2004 — Clozapine is effective in treating drug-induced psychosis in Parkinson's disease (PD), according to the results of a randomized trial published in the May issue of the Journal of Neurology, Neurosurgery and Psychiatry.

"At least 32 open labelled trials involving more than 300 patients have suggested the usefulness of the atypical neuroleptic clozapine as a unique possibility of controlling drug induced psychosis, without compromising motor function, in many patients with PD," write P. Pollak, from University Hospital of Grenoble in France, and colleagues from the French Clozapine Parkinson Study Group. "The efficacy and tolerability of low dose clozapine in the treatment of drug induced psychosis in PD has recently been outlined in the first double-blind, placebo-controlled study."

In this large, multicenter study, 60 patients with PD underwent a four-week, randomized, double-blind, parallel comparison of clozapine and placebo, followed by a 12-week clozapine open period, then a one-month period of evaluation after drug discontinuation. At the end of the double-blind period, the mean dose of clozapine was 35.8 mg (range, 12.5 - 50.0 mg).

The mean Clinical Global Impression Scale (CGI) score, which was the primary efficacy outcome, improved by 1.8 ± 1.5 in the clozapine group and by 0.6 ± 1.1 in the placebo group (P = .001). The mean positive subscore of the Positive and Negative Syndrome Scale (PANSS) improved by 5.6 ± 3.9 in the clozapine group and by 0.8 ± 2.8 in the placebo group (P < .0001).

At the end of the open period, 25 patients had completely recovered from delusions and hallucinations, and 19 patients experienced a relapse within one month after clozapine washout. Scores on the Unified PD Rating Scale (UPDRS) and the Mini-Mental State Examination (MMSE), which were used as safety outcomes, did not change significantly in either group. Somnolence occurred more frequently with clozapine than with placebo.

"Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops," the authors write. "Because of the risk of agranulocytosis with clozapine, regular and long term blood cell counts are mandatory, and treatment should only be started if the usual therapeutic approach has failed. Although cost efficacy studies remain to be performed, one would expect them to be favourable because of the heavy cost of multiple hospitalisations and the institutionalisation rate linked to dopaminomimetic induced psychosis."

Novartis sponsored this study, employs two of its authors, and has various financial arrangements with four other authors.

J Neurol Neurosurg Psychiatry. 2004;75:689-695

Reviewed by Gary D. Vogin, MD


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