Dyskinesias commonly appear during L-
dihydroxyphenylalanine (
L-DOPA)
therapy of advanced
Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns.
Clozapine exerts a dose-related suppression of
L-DOPA-induced
dyskinesias by shifting the i.v.
L-DOPA dose-response curve for production of
dyskinesias without altering relief of
parkinsonism. We report our outpatient experience with 13 patients on daily
clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of
clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with
dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients.
Orthostatic hypotension and
sialorrhea were variably present. No patients had
seizures, bone marrow toxicity, or detectable loss of efficacy of
clozapine with chronic use. We conclude that
clozapine is an effective agent for suppression of
dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.