Clozapine versus placebo in Huntington's disease: A double blind randomised comparative study

Objectives - To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease. Methods - Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for 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 Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. 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 separately. Results - Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients 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 disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties. Conclusions - Clozapine 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 should be used with restraint in this patient group.