Clozapine: new preparation. A last resort for parkinsonian patients with psychosis.

(1) Psychotic disorders occurring in patients with Parkinson's disease are usually linked to antiparkinsonian treatments. Tapering the dose of dopaminergic or anticholinergic drugs does not always yield a satisfactory balance between the psychotic and motor disorders. Most neuroleptics tend to worsen extrapyramidal manifestations and are contraindicated in combination with dopaminergic agents. Their assessment in patients with Parkinson's disease has been limited. (2) Clozapine, a neuroleptic, is now indicated in this type of patient. (3) The evidence comes from two double-blind placebo-controlled trials, each involving 60 patients. In these trials, 40% of patients lost all their psychotic disorders on low-dose clozapine, usually with no worsening of parkinsonian manifestations. (4) In clinical trials of clozapine in Parkinson's disease, the incidence of neutropenia was between 2 and 3%, and that of agranulocytosis 0.3%. The risks of myocarditis, dilated myocardiopathy and malignant neuroleptic syndrome associated with clozapine call for strict pharmacovigilance. (5) In practice, when adjusting antiparkinsonian treatment fails to strike a balance between psychotic and parkinsonism disorders, clozapine is the standard neuroleptic. It should be used with care, however, because of its adverse effects.