Introduction: Chronic administration of dopaminomimetic drugs, levodopa before all, to patients with Parkinson's disease (PD) is accompanied with numerous complications. Psychiatric complications are not only frequent, but also difficult to manage. Reduction of the daily dose or complete discontinuation of dopaminomimetic therapy and usage of conventional neuroleptic drugs may relieve the psychotic symptoms, but both these approaches are associated with unacceptable deterioration of motor symptoms. The aim of the study is to present our experience in the treatment of levodopa-induced psychoses by clozapine in patients with PD. Clozapine is a non-typical antipsychotic drug with low potential fr inducing extrapyramidal symptoms.
Methods: A two-year open study in which clozapine was used as the treatment of choice covered 16 patients with PD and psychosis (8.7% of all patients with PD treated at the Department of CNS Degenerative Diseases, Institute of Neurology, Clinical Centre of Serbia, Belgrade). All patients presented for examination with psychotic manifestations whose severity necessitated hospitalization so that the whole study was conducted on the in-patient basis. Patients with haematological disorders, history of epileptic seizures or major dysfunction of the heart, liver and kidneys were not included in the study. In none of the patients EEG records suggested epileptic focl or other major disorders. The stage of PD was determined according to Hoehn and Yahr scale. After the comprehensive evaluation, the treatment was initiated with a bedtime dose of 6.25-12.5 mg clozapine, with gradual increase in 6.25 mg increments in two or three day intervals until the dose which optimally relieved the psychotic symptoms. The levodopa doses were not reduced, except in cases when clozapine action was not satisfactory after the 50 mg dose had been reached. The patients were subjected to daily evaluation of therapeutic response and adverse effects (particularly in the first 19 days) while the blood count and leukocyte formula were determined twice a week.
Results: A group of 16 patients with PD consisted of 7 women and 9 men, average age 64.8 years (range 51-72), and average duration of PD 13.7 years (range 7-19). All patients received the combination of levodopa and benserazide, mean dose 875.5 mg (range 500-1250 mg), while eight patients received bromocriptine (15 mg), as well. Relief of psychotic symptoms was achieved in 12 (75%) patients in whom the improvement was manifest 5-7 days after the onset of clozapine therapy. The average daily dose of clozapine in this group of patients was 30 mg (range 12.5-100 mg) which was continued even after the discharge of the patients, in the follow-up period of 6-18 months, with unchanged effect. In two patients the therapy was discontinued due to marked orthostatic hypotension and somnolence. In another two patients (13%) the therapy failed to induce the desired effect in spite of the clozapine dose increase to 300 mg.
Discussion: The basic conclusion of our study is that clozapine effectively suppresses levodopa-induced psychoses in patients with PD. Low daily doses are required, while no reduction of levodopa and other dopaminomimetic drugs is needed. Thus, antipsychotic action of clozapine does not affect the treatment of the underlying disease, i.e. relief of parkinsonism.