SUPPRESSION OF DYSKINESIAS IN ADVANCED PARKINSONS-DISEASE - MODERATE DAILY CLOZAPINE DOSES PROVIDE LONG-TERM DYSKINESIA REDUCTION

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) t herapy of advanced Parkinson's disease (PD) and can occur in both dose -related and dose-independent patterns. Clozapine exerts a dose-relate d suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOP A dose-response curve for production of dyskinesias without altering r elief of parkinsonism. We report our outpatient experience with 13 pat ients on daily clozapine therapy (maximum dose 400 mg/day), followed f or 3-21 months (median 10). Beneficial effects of clozapine, determine d from twice-weekly diaries, included increased ''on time'' and decrea sed ''off time'' and time ''on with dyskinesia.'' Improvements were st atistically 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 presen t. 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 eff ective daily dose for most patients of 100-200 mg/day.