CLOZAPINE VERSUS PLACEBO IN HUNTINGTONS-DISEASE - A DOUBLE-BLIND RANDOMIZED COMPARATIVE-STUDY

Objectives-To establish the effect of the atypical neuroleptic clozapi ne on chorea, voluntary motor performance, and functional disability i n patients with Huntington's disease. Methods-Thirty three patients wi th Huntington's disease participated in a double blind randomised tria l. A maximum of 150 mg/day clozapine or placebo equivalent was given f or a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Hu ntington's disease rating scale (UHDRS), and judgement of video record ings. Voluntary motor performance was assessed using the UHDRS motor s cale. Patients and their partners completed a questionnaire regarding functional disability, Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed se parately. Results-Clozapine tended to reduce chorea in neuroleptic nai ve patients only (AIMS); improvement seemed more pronounced in patient s receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine . Neuroleptic naive patients reported aggravation of functional disabi lity, possibly reflecting the frequent occurrence of side effects. Adv erse reactions forced trial termination in six patients and dose reduc tion in another eight, and consisted mainly of drowsiness, fatigue, an ticholinergic symptoms, and walking difficulties. Conclusions-Clozapin e has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine sho uld be used with restraint in this patient group.