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Clozapine versus placebo in Huntington's disease: a double blindrandomised comparative study |
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| Authors: | J P P van Vugt S Siesling M Vergeer E A van der Velde R Roos |
| Affiliation: | Department of Neurology, Leiden University Medical Centre, The Netherlands. |
| Abstract: | OBJECTIVES—To establish the effect of theatypical neuroleptic clozapine on chorea, voluntary motor performance,and functional disability in patients with Huntington's disease. METHODS—Thirty three patients withHuntington's disease participated in a double blindrandomised trial. A maximum of 150 mg/day clozapine or placeboequivalent was given for a period of 31 days. Assessments wereperformed in the week before and at the last day of the trial. Choreawas scored using the abnormal involuntary movement scale (AIMS), thechorea score of the unified Huntington's disease rating scale (UHDRS),and judgement of video recordings. Voluntary motor performance wasassessed using the UHDRS motor scale. Patients and their partnerscompleted a questionnaire regarding functional disability. Twelvepatients already used other neuroleptic medication, which was keptunchanged during the trial period. Results of neuroleptic naive andneuroleptic treated patients were analysed separately. RESULTS—Clozapine tended to reduce chorea inneuroleptic naive patients only (AIMS); improvement seemed morepronounced in patients receiving higher doses of clozapine. Othermeasures of chorea (UHDRS chorea score, video ratings) showed noimprovement. Clozapine had no beneficial effect on chorea in patientsalready receiving neuroleptic medication. Voluntary motor performancedid not improve with clozapine. Neuroleptic naive patients reportedaggravation of functional disability, possibly reflecting the frequentoccurrence of side effects. Adverse reactions forced trial terminationin six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties. CONCLUSIONS—Clozapine has little beneficialeffect in patients withHuntington's disease, although individual patients may toleratedoses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group. |
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