Clozapine reduces drug-induced psychosis in Parkinson's disease

Main Category: Public Health
Article Date: 18 May 2004 - 0:00 PDT

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People with Parkinson's disease (PD) who develop psychotic symptoms as a result of their medication could benefit from taking low-dose clozapine, which reduces such symptoms without compromising motor function, researchers have found.

Following promising results from previous open-labelled trials, Pierre Pollack (Centre Hospitalier Universitaire de Grenoble, France) and colleagues carried out a double-blind trial in which 60 PD patients were randomly assigned to receive clozapine (12.5 to 50 mg/day) or placebo for 4 weeks. This was followed by a 12-week clozapine open period, along with 1 month's follow-up after drug discontinuation.

In all, 46 patients completed the treatment phase, and among the 32 patients taking clozapine, scores on the Clinical Global Impression Scale improved by an average of 1.8, compared with just 0.6 for those taking placebo.

Scores on the positive subscale of the Positive and Negative Syndrome Scale also improved more in the clozapine-treated group, at an average of 5.6 versus 0.8 for placebo-treated individuals. At the end of the open period, 25 patients had completely recovered from delusions and hallucinations.

Among the 25 patients who entered the withdrawal phase, 12 patients relapsed within 1 week, seven within 1 month, and three after 3 months.

Clozapine was generally well tolerated, with no differences seen between the two groups with regard to rates of adverse events, or scores on the Unified Parkinson's Rating Scale, and the Mini-Mental State Examination.

"Our trial confirms that clozapine is an effective treatment of the psychotic complications induced by dopaminomimetic drugs, which does not significantly compromise motor and cognitive functions provided doses are less than 50 mg/day," say Pollack and team in the Journal of Neurology, Neurosurgery, and Psychiatry.

They note, however, that, "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."

http://jnnp.bmjjournals.com/cgi/content/abstract/75/5/689

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

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