Treatment of Huntington Disease
MOVEMENT DISORDERS (O SUCHOWERSKY, SECTION EDITOR)
First Online: 16 February 2013 DOI:
Cite this article as: Videnovic, A. Curr Treat Options Neurol (2013) 15: 424. doi:10.1007/s11940-013-0219-8 Opinion statement
Many pharmacological agents have been utilized in the treatment of Huntington disease (HD). Several excellent reviews about the treatment of HD are available. Formal treatment guidelines are however lacking. This is mainly the result of limited evidence available in the literature. Further, available treatment studies are frequently hard to compare due to variable outcomes/instruments used, differences in the study population, and confounding effects of complex medication regimens. Generally speaking, the treatment paradigm for an HD patient will depend on the constellation of 3 main clinical domains affected in HD: motor, behavioral/psychiatric, and cognitive. Symptoms within each of these domains remain dynamic throughout the course of HD. It is therefore necessary to monitor patients clinically and adjust drugs accordingly as the disease progresses. The most commonly used chorea drugs are antipsychotics and tetrabenazine (TBZ). Antipsychotic drugs are preferred in patients with coexistent psychiatric/behavioral comorbidities as well as in the presence of depression. Amantadine may be considered in the treatment of chorea, but data supporting its effectiveness remain conflicting. Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for irritability and obsessive-compulsive behaviors associated with HD. Antipsychotic agents and antiepileptic mood stabilizers may be used as add-on therapies. There is very limited evidence for the treatment of cognitive impairment associated with HD. Each drug used in treatment of HD has a potential for causing significant side effects. It is, therefore, critical to assess the risk-benefit ratio on an individual basis, and carefully monitor patients throughout the course of treatment. Non-pharmacological and surgical treatment strategies for HD have not been systematically explored. Despite the lack of evidence, behavioral interventions, as well as physical, occupational, and speech therapies may provide additional benefits to a wide spectrum of disabilities associated with HD.
Keywords Huntington disease Treatment Chorea Antidopaminergic agents Antipsychotics Haloperidol NDA receptor antagonists Cognitive dysfunction Behavioral disturbances Psychosis Deep brain stimulation References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group
. Cell. 1993;72(6):971–83.
Mahant N, McCusker EA, Byth K, Graham S. Huntington's disease: clinical correlates of disability and progression. Neurology. 2003;61(8):1085–92.
Di Maio L, Squitieri F, Napolitano G, et al. Onset symptoms in 510 patients with Huntington's disease. J Med Genet. 1993;30(4):289–92.
Paulsen JS, Ready RE, Hamilton JM, et al. Neuropsychiatric aspects of Huntington's disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310–4.
Litvan I, Paulsen JS, Mega MS, Cummings JL. Neuropsychiatric assessment of patients with hyperkinetic and hypokinetic movement disorders. Arch Neurol. 1998;55(10):1313–9.
Ho AK, Sahakian BJ, Brown RG, et al. Profile of cognitive progression in early Huntington's disease. Neurology. 2003;61(12):1702–6.
Bamford KA, Caine ED, Kido DK, et al. A prospective evaluation of cognitive decline in early Huntington's disease: functional and radiographic correlates. Neurology. 1995;45(10):1867–73.
Fernandez HH, Friedman JH, Grace J, Beason-Hazen S. Donepezil for Huntington's disease. Mov Disord. 2000;15(1):173–6.
de Tommaso M, Specchio N, Sciruicchio V, et al. Effects of rivastigmine on motor and cognitive impairment in Huntington's disease. Mov Disord. 2004;19(12):1516–8.
Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366–72. Important recent Class I evidence treatment study on TBZ in HD.
Frank S. Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators. BMC Neurol. 2009;9:62.
Kenney C, Hunter C, Davidson A, Jankovic J. Short-term effects of tetrabenazine on chorea associated with Huntington's disease. Mov Disord. 2007;22(1):10–3.
Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology. 1997;48(2):358–62.
Ondo WG, Tintner R, Thomas M, Jankovic J. Tetrabenazine treatment for Huntington's disease-associated chorea. Clin Neuropharmacol. 2002;25(6):300–2.
Koller WC, Trimble J. The gait abnormality of Huntington's disease. Neurology. 1985;35(10):1450–4.
Girotti F, Carella F, Scigliano G, et al. Effect of neuroleptic treatment on involuntary movements and motor performances in Huntington's disease. J Neurol Neurosurg Psychiatry. 1984;47(8):848–52.
McArthur AW, Pollock M, Smidt NA. Combined therapy with tetrabenazine and pimozide in Huntington's chorea: pilot study. N Z Med J. 1976;83(558):114–6.
van Vugt JP, Siesling S, Vergeer M, et al. Clozapine vs placebo in Huntington's disease: a double blind randomized comparative study. J Neurol Neurosurg Psychiatry. 1997;63(1):35–9. Class I evidence treatment study on clozapine in HD.
Bonuccelli U, Ceravolo R, Maremmani C, et al. Clozapine in Huntington's chorea. Neurology. 1994;44(5):821–3.
Vallette N, Gosselin O, Kahn JP. Efficacy of clozapine in the course of Huntington chorea: apropos of a clinical case. Encephale. 2001;27(2):169–71.
Colosimo C, Cassetta E, Bentivoglio AR, Albanese A. Clozapine in Huntington's disease. Neurology. 1995;45(5):1023–4.
Bonelli RM, Mahnert FA, Niederwieser G. Olanzapine for Huntington's disease: an open label study. Clin Neuropharmacol. 2002;25(5):263–5.
Bogelman G, Hirschmann S, Modai I. Olanzapine and Huntington's disease. J Clin Psychopharmacol. 2001;21(2):245–6.
Bonelli RM, Niederwieser G, Diez J, Koltringer P. Riluzole and olanzapine in Huntington's disease. Eur J Neurol. 2002;9(2):183–4.
Bonelli RM, Niederwieser G, Tribl GG, Koltringer P. High-dose olanzapine in Huntington's disease. Int Clin Psychopharmacol. 2002;17(2):91–3.
Dipple HC. The use of olanzapine for movement disorder in Huntington's disease: a first case report. J Neurol Neurosurg Psychiatry. 1999;67(1):123–4.
Etchebehere EC, Lima MC, Passos W, et al. Brain SPECT imaging in Huntington's disease before and after therapy with olanzapine. Case report. Arq Neuropsiquiatr. 1999;57(3B):863–6.
Grove Jr VE, Quintanilla J, DeVaney GT. Improvement of Huntington's disease with olanzapine and valproate. N Engl J Med. 2000;343(13):973–4.
Jimenez-Jimenez FJ, de Toledo M, Puertas I, et al. Olanzapine improves chorea in patients with Huntington's disease. Rev Neurol. 2002;35(6):524–5.
Laks J, Rocha M, Capitao C, et al. Functional and motor response to low dose olanzapine in Huntington's disease: case report. Arq Neuropsiquiatr. 2004;62(4):1092–4.
Bonelli RM, Mayr BM, Niederwieser G, et al. Ziprasidone in Huntington's disease: the first case reports. J Psychopharmacol. 2003;17(4):459–60.
Brusa L, Orlacchio A, Moschella V, et al. Treatment of the symptoms of Huntington's disease: preliminary results comparing aripiprazole and tetrabenazine. Mov Disord. 2009;24(1):126–9.
Ciammola A, Sassone J, Colciago C, et al. Aripiprazole in the treatment of Huntington's disease: a case series. Neuropsychiatr Dis Treat. 2009;5:1–4.
Parsa MA, Szigethy E, Voci JM, Meltzer HY. Risperidone in treatment of choreoathetosis of Huntington's disease. J Clin Psychopharmacol. 1997;17(2):134–5.
Dallocchio C, Buffa C, Tinelli C, Mazzarello P. Effectiveness of risperidone in Huntington chorea patients. J Clin Psychopharmacol. 1999;19(1):101–3.
Bonelli RM, Niederwieser G. Quetiapine in Huntington's disease: a first case report. J Neurol. 2002;249(8):1114–5.
Verhagen Metman L, Morris MJ, Farmer C, et al. Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694–9.
Lucetti C, Del Dotto P, Gambaccini G, et al. IV amantadine improves chorea in Huntington's disease: an acute randomized, controlled study. Neurology. 2003;60(12):1995–7.
Heckmann JM, Legg P, Sklar D, et al. IV amantadine improves chorea in Huntington's disease: an acute randomized, controlled study. Neurology. 2004;63(3):597–8. author reply 597–8.
O'Suilleabhain P, Dewey Jr RB. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60(7):996–8.
Ondo WG, Mejia NI, Hunter CB. A pilot study of the clinical efficacy and safety of memantine for Huntington's disease. Parkinsonism Relat Disord. 2007;13(7):453–4.
Puri BK, Leavitt BR, Hayden MR, et al. Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial. Neurology. 2005;65(2):286–92.
Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study. Arch Neurol. 2008;65(12):1582–9.
de Tommaso M, Difruscolo O, Sciruicchio V, et al. Two years' follow-up of rivastigmine treatment in Huntington disease. Clin Neuropharmacol. 2007;30(1):43–6.
Cubo E, Shannon KM, Tracy D, et al. Effect of donepezil on motor and cognitive function in Huntington disease. Neurology. 2006;67(7):1268–71.
Fernandez HH, Friedman JH, Grace J, Beason-Hazen S. Donepezil for Huntington's disease. Mov Disord. 2000;15(1):173–6.
Como PG, Rubin AJ, O'Brien CF, et al. A controlled trial of fluoxetine in nondepressed patients with Huntington's disease. Mov Disord. 1997;12(3):397–401.
Holl AK, Wilkinson L, Painold A, et al. Combating depression in Huntington's disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25(1):46–50.
Bonelli RM. Mirtazapine in suicidal Huntington's disease. Ann Pharmacother. 2003;37(3):452.
Sajatovic M, Verbanac P, Ramirez LF, Meltzer HY. Clozapine treatment of psychiatric symptoms resistant to neuroleptic treatment in patients with Huntington's chorea. Neurology. 1991;41(1):156.
Erdemoglu AK, Boratav C. Risperidone in chorea and psychosis of Huntington's disease. Eur J Neurol. 2002;9(2):182–3.
Madhusoodanan S, Brenner R. Use of risperidone in psychosis associated with Huntington's disease. Am J Geriatr Psychiatry. 1998;6(4):347–9.
Squitieri F, Cannella M, Piorcellini A, et al. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69–72.
Paleacu D, Anca M, Giladi N. Olanzapine in Huntington's disease. Acta Neurol Scand. 2002;105(6):441–4.
Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington's disease. Psychosomatics. 2006;47(1):70–2.
Ranen NG, Lipsey JR, Treisman G, Ross CA. Sertraline in the treatment of severe aggressiveness in Huntington's disease. J Neuropsychiatry Clin Neurosci. 1996;8(3):338–40.
Bhandary AN, Masand PS. Buspirone in the management of disruptive behaviors due to Huntington's disease and other neurological disorders. Psychosomatics. 1997;38(4):389–91.
Byrne A, Martin W, Hnatko G. Beneficial effects of buspirone therapy in Huntington's disease. Am J Psychiatry. 1994;151(7):1097.
Findling RL. Treatment of aggression in juvenile-onset Huntington's disease with buspirone. Psychosomatics. 1993;34(5):460–1.
Stewart JT, Mounts ML, Clark Jr RL. Aggressive behavior in Huntington's disease: treatment with propranolol. J Clin Psychiatry. 1987;48(3):106–8.
Stewart JT. Paradoxical aggressive effect of propranolol in a patient with Huntington's disease. J Clin Psychiatry. 1987;48(9):385–6.
Kang GA, Heath S, Rothlind J, Starr PA. Long-term follow-up of pallidal deep brain stimulation in two cases of Huntington's disease. J Neurol Neurosurg Psychiatry. 2011;82(3):272–7.
Biolsi B, Cif L, Fertit HE, et al. Long-term follow-up of Huntington disease treated by bilateral deep brain stimulation of the internal globus pallidus. J Neurosurg. 2008;109(1):130–2.
Fasano A, Mazzone P, Piano C, et al. GPi-DBS in Huntington's disease: results on motor function and cognition in a 72-year-old case. Mov Disord. 2008;23(9):1289–92.
Moro E, Lang AE, Strafella AP, et al. Bilateral globus pallidus stimulation for Huntington's disease. Ann Neurol. 2004;56(2):290–4.
PubMed CrossRef Copyright information
© Springer Science+Business Media New York 2013