Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1997 Jul;63(1):35–39. doi: 10.1136/jnnp.63.1.35

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

J P P van Vugt 1, S Siesling 1, M Vergeer 1, E A van der Velde 1, R Roos 1
PMCID: PMC2169648  PMID: 9221965

Abstract

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.



Full Text

The Full Text of this article is available as a PDF (96.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albin R. L., Reiner A., Anderson K. D., Penney J. B., Young A. B. Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia. Ann Neurol. 1990 Apr;27(4):357–365. doi: 10.1002/ana.410270403. [DOI] [PubMed] [Google Scholar]
  2. Alexander G. E., Crutcher M. D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266–271. doi: 10.1016/0166-2236(90)90107-l. [DOI] [PubMed] [Google Scholar]
  3. Baldessarini R. J., Frankenburg F. R. Clozapine. A novel antipsychotic agent. N Engl J Med. 1991 Mar 14;324(11):746–754. doi: 10.1056/NEJM199103143241107. [DOI] [PubMed] [Google Scholar]
  4. Bonuccelli U., Ceravolo R., Maremmani C., Nuti A., Rossi G., Muratorio A. Clozapine in Huntington's chorea. Neurology. 1994 May;44(5):821–823. doi: 10.1212/wnl.44.5.821. [DOI] [PubMed] [Google Scholar]
  5. Brown R. G., MacCarthy B., Jahanshahi M., Marsden C. D. Accuracy of self-reported disability in patients with parkinsonism. Arch Neurol. 1989 Sep;46(9):955–959. doi: 10.1001/archneur.1989.00520450025014. [DOI] [PubMed] [Google Scholar]
  6. Caine E. D., Polinsky R. J., Kartzinel R., Ebert M. H. The trial use of clozapine for abnormal involuntary movement disorders. Am J Psychiatry. 1979 Mar;136(3):317–320. doi: 10.1176/ajp.136.3.317. [DOI] [PubMed] [Google Scholar]
  7. Colosimo C., Cassetta E., Bentivoglio A. R., Albanese A. Clozapine in Huntington's disease. Neurology. 1995 May;45(5):1023–1024. doi: 10.1212/wnl.45.5.1023. [DOI] [PubMed] [Google Scholar]
  8. Crossman A. R. Neural mechanisms in disorders of movement. Comp Biochem Physiol A Comp Physiol. 1989;93(1):141–149. doi: 10.1016/0300-9629(89)90201-6. [DOI] [PubMed] [Google Scholar]
  9. Deroover J., Baro F., Bourguignon R. P., Smets P. Tiapride versus placebo: a double-blind comparative study in the management of Huntington's chorea. Curr Med Res Opin. 1984;9(5):329–338. doi: 10.1185/03007998409109601. [DOI] [PubMed] [Google Scholar]
  10. Farde L., Nordström A. L. PET analysis indicates atypical central dopamine receptor occupancy in clozapine-treated patients. Br J Psychiatry Suppl. 1992 May;(17):30–33. [PubMed] [Google Scholar]
  11. Feigin A., Kieburtz K., Bordwell K., Como P., Steinberg K., Sotack J., Zimmerman C., Hickey C., Orme C., Shoulson I. Functional decline in Huntington's disease. Mov Disord. 1995 Mar;10(2):211–214. doi: 10.1002/mds.870100213. [DOI] [PubMed] [Google Scholar]
  12. Gerfen C. R., Engber T. M., Mahan L. C., Susel Z., Chase T. N., Monsma F. J., Jr, Sibley D. R. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990 Dec 7;250(4986):1429–1432. doi: 10.1126/science.2147780. [DOI] [PubMed] [Google Scholar]
  13. Girotti F., Carella F., Scigliano G., Grassi M. P., Soliveri P., Giovannini P., Parati E., Caraceni T. Effect of neuroleptic treatment on involuntary movements and motor performances in Huntington's disease. J Neurol Neurosurg Psychiatry. 1984 Aug;47(8):848–852. doi: 10.1136/jnnp.47.8.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jann M. W., Grimsley S. R., Gray E. C., Chang W. H. Pharmacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinet. 1993 Feb;24(2):161–176. doi: 10.2165/00003088-199324020-00005. [DOI] [PubMed] [Google Scholar]
  15. Kane J., Honigfeld G., Singer J., Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988 Sep;45(9):789–796. doi: 10.1001/archpsyc.1988.01800330013001. [DOI] [PubMed] [Google Scholar]
  16. Klawans H. L. Chorea. Can J Neurol Sci. 1987 Aug;14(3 Suppl):536–540. doi: 10.1017/s0317167100038075. [DOI] [PubMed] [Google Scholar]
  17. Klockgether T., Dichgans J. Do neuroleptic drugs still have a place in neurological therapy? J Neurol. 1990 Jul;237(4):221–225. doi: 10.1007/BF00314622. [DOI] [PubMed] [Google Scholar]
  18. Naber D., Holzbach R., Perro C., Hippius H. Clinical management of clozapine patients in relation to efficacy and side-effects. Br J Psychiatry Suppl. 1992 May;(17):54–59. [PubMed] [Google Scholar]
  19. Penney J. B., Jr, Young A. B. Striatal inhomogeneities and basal ganglia function. Mov Disord. 1986;1(1):3–15. doi: 10.1002/mds.870010102. [DOI] [PubMed] [Google Scholar]
  20. Quinn N., Marsden C. D. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia. J Neurol Neurosurg Psychiatry. 1984 Aug;47(8):844–847. doi: 10.1136/jnnp.47.8.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reiner A., Albin R. L., Anderson K. D., D'Amato C. J., Penney J. B., Young A. B. Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5733–5737. doi: 10.1073/pnas.85.15.5733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sajatovic M., Verbanac P., Ramirez L. F., Meltzer H. Y. Clozapine treatment of psychiatric symptoms resistant to neuroleptic treatment in patients with Huntington's chorea. Neurology. 1991 Jan;41(1):156–156. doi: 10.1212/wnl.41.1.156. [DOI] [PubMed] [Google Scholar]
  23. Schott K., Ried S., Stevens I., Dichgans J. Neuroleptically induced dystonia in Huntington's disease: a case report. Eur Neurol. 1989;29(1):39–40. doi: 10.1159/000116375. [DOI] [PubMed] [Google Scholar]
  24. Sedvall G. PET imaging of dopamine receptors in human basal ganglia: relevance to mental illness. Trends Neurosci. 1990 Jul;13(7):302–308. doi: 10.1016/0166-2236(90)90114-p. [DOI] [PubMed] [Google Scholar]
  25. Seeman P., Van Tol H. H. Dopamine receptor pharmacology. Trends Pharmacol Sci. 1994 Jul;15(7):264–270. doi: 10.1016/0165-6147(94)90323-9. [DOI] [PubMed] [Google Scholar]
  26. Shoulson I. Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. Neurology. 1981 Oct;31(10):1333–1335. doi: 10.1212/wnl.31.10.1333. [DOI] [PubMed] [Google Scholar]
  27. Storey E., Beal M. F. Neurochemical substrates of rigidity and chorea in Huntington's disease. Brain. 1993 Oct;116(Pt 5):1201–1222. doi: 10.1093/brain/116.5.1201. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES