[Clozapine in the treatment of mental manifestations of Parkinson disease]

Abstract

Background: Medical treatment of Parkinsonian syndromes is often complicated by psychiatric side effects such as confusional states, hallucinations and psychosis. Recent pilot studies report good clinical results with the atypical neuroleptic clozapine.

Patients and methods: We report on 15 patients with Parkinsonian syndromes: 11 with idiopathic Parkinson's disease (IPD), 3 with multiple system atrophy (MSA) and 1 with postencephalitic Parkinsonism (SPP). The mean age was 68.8 +/- 10 years; the mean duration of Parkinsonian symptoms was 6.8 +/- 5.7 years. The Hoehn & Yahr grade was: 3.5 +/- 0.8. Eleven patients were suffering from psychotic episodes, 10 from hallucinations, 8 from confusional states. Clozpine was introduced at nighttime and dosage was modified until the appearance of clinical effect or intolerable side effects.

Results: We report on an observed cumulative duration of clozapine treatment of 13 patient-years. The average treatment duration was 10.5 +/- 10.4 months. The mean daily dose was 33.3 +/- 30 mg (range: 6.2-100). There was at least transitory improvement of psychiatric symptoms in all patients. There was constant and complete improvement in 7 patients (46%) and satisfactory improvement in 5 patients (33.3%). The levodopa dosage was unchanged (mean dosage 563 +/- 232 mg), and the dosage of dopamine agonists was significantly increased. None of our patients experienced motor deterioration. Side effects comprised sialorrhoea, sedation, orthostatic hypotension, and delirium tremens and an epileptic seizure in one patient each. Two patients died suddenly at the 63rd and at the 86th day of treatment respectively, outside the hospital. These deaths seemed to be unrelated to the treatment. There was no agranulocytosis.

Conclusion: Clozapine is an efficient antipsychotic drug in Parkinsonian patients with no motor side effects in the dosages used. The effective dosage is very low in comparison to psychiatric patients. However various side effects may occur and close monitoring is required.