Therapeutics in Huntington’s Disease
Cognitive Disorders (M Geschwind, Section Editor)
First Online: 08 February 2012 DOI:
Cite this article as: Killoran, A. & Biglan, K.M. Curr Treat Options Neurol (2012) 14: 137. doi:10.1007/s11940-012-0165-x Opinion statement
There is no specific treatment for Huntington’s disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient’s professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD’s complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there may be need for other specialists, such as a speech and occupational therapist, a nutritionist for weight loss, and ultimately, a palliative care specialist.
Keywords Huntington’s disease Huntington disease Chorea Treatment Therapy Tetrabenazine Neuroleptics Haloperidol Juvenile Huntington’s disease Pharmacologic treatment Trinucleotide repeat disorder References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance
Huntington G. On chorea. Med Surg Rep. 1872;26:317–21.
The Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72:971–83.
Hodgson JG, Agopyan N, Gutekunst CA, et al. A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron. 1999;23:181–92.
Walker FO. Huntington’s disease. Lancet. 2007;369:218–28.
Venuto CS, McGarry A, Ma Q, Kieburtz K. Pharmacologic approaches to the treatment of Huntington’s disease. Mov Disord. 2011 Oct 13 (Epub ahead of print). This is a recent detailed review of the pharmacological aspects of the medications currently used in HD and of those being evaluated for future use.
Adam OR, Jankovic J. Symptomatic treatment of Huntington disease. Neurotherapeutics. 2008;5:181–97.
Phillips W, Shannon KM, Barker RA. The current clinical management of Huntington’s disease. Mov Disord. 2008;23:1491–504.
Ross CA, Tabrizi SJ. Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 2011;10(1):83–98.
Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66:366–72.
Poon LH. Role of tetrabenazine for Huntington’s disease-associated chorea. Ann Pharmacother. 2010;44:1080–9.
Bonelli RM, Mahnert FA, Niederwieser G. Olanzapine for Huntington’s disease: an open label study. Clin Neuropharmacol. 2002;25:263–5.
Squitieri F, Cannella M, Piorcellini A, et al. Shortterm effects of olanzapine in Huntington’s disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14:69–72.
Dallocchio C, Buffa C, Tinelli C, Mazzarello P. Effectiveness of risperidone in Huntington chorea patients. J Clin Psychopharmacol. 1999;19:101–3.
Duff K, Beglinger LJ, O’Rourke ME, et al. Risperidone and the treatment of psychiatric, motor, and cognitive symptoms in Huntington’s disease. Ann Clin Psychiatry. 2008;20:1–3.
Giménez-Roldán S, Mateo D. Huntington disease: tetrabenazine compared to haloperidol in the reduction of involuntary movements. Neurologia. 1989;4:282–7.
Peiris JB, Boralessa H, Lionel ND. Clonazepam in the treatment of choreiform activity. Med J Aust. 1976;1:225–7.
Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics. 2006;47:70–2.
Saft C, Lauter T, Kraus PH, et al. Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington’s Disease patients: a case series. BMC Neurol. 2006;6:11.
Holl AK, Wilkinson L, Painold A, et al. Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25:46–50.
Duan W, Peng Q, Masuda N, et al. Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington’s disease. Neurobiol Dis. 2008;30:312–22.
Duan W, Guo Z, Jiang H, et al. Paroxetine retards disease onset and progression in Huntingtin mutant mice. Ann Neurol. 2004;55:590–4.
de Tommaso M, Specchio N, Sciruicchio V, et al. Effects of rivastigmine on motor and cognitive impairment in Huntington’s disease. Mov Disord. 2004;19:1516–8.
de Tommaso M, Difruscolo O, Sciruicchio V, et al. Two years’ follow-up of rivastigmine treatment in Huntington disease. Clin Neuropharmacol. 2007;30:43–6.
Cubo E, Shannon KM, Tracy D, et al. Effect of donepezil on motor and cognitive function in Huntington disease. Neurology. 2006;67:1268–71.
Brown GR. The use of methylphenidate for cognitive decline associated with HIV disease. Int J Psychiatry Med. 1995;25:21–37.
Brown TE, Landgraf JM. Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgrad Med. 2010;122:42–51.
Beglinger LJ, Adams WH, Paulson H, et al. Randomized controlled trial of atomoxetine for cognitive dysfunction in early Huntington disease. J Clin Psychopharmacol. 2009;29:484–7.
Tan E, Jankovic J, Ondo W. Bruxism in Huntington’s disease. Mov Disord. 2000;15:171–3.
Burbaud P, Ducerf C, Cugy E, et al. Botulinum toxin treatment in neurological practice: how much does it really cost? A prospective cost-effectiveness study. J Neurol. 2011;258:1670–5.
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;13:453–4.
Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington’s disease. Neurology. 2001;57:397–404.
Hersch SM, Gevorkian S, Marder K, et al. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG. Neurology. 2006;66:250–2.
de Yebenes JG, Landwehrmeyer B, Squitieri F, et al. on behalf of the MermaiHD study investigators. Pridopidine for the treatment of motor function in patients with Huntington’s disease: a phase 3, randomised, placebo-controlled trial. Lancet Neurol. 2011;10:1049–57.
Zeef D, Schaper F, Vlamings R, et al. Deep brain stimulation in Huntington’s disease: the current status. Open Neurosurg J. 2011;4:7–10.
Hauser RA, Furtado S, Cimino CR, et al. Bilateral human fetal striatal transplantation in Huntington’s disease. Neurology. 2002;58:687–95.
Southwell AL, Patterson PH. Gene therapy in mouse models of Huntington disease. Neuroscientist. 2011;17:153–62.
Jongen P, Renier W, Gabreels F. Seven cases of Huntington’s disease in childhood and levodopa induced improvement in the hypokinetic—rigid form. Clin Neurol Neurosurg. 1980;82:251–61.
Striano P, Manganelli F, Boccella P, et al. Levetiracetam in patients with cortical myoclonus: a clinical and electrophysiological study. Mov Disord. 2005;20:1610–4.
de Tommaso M, Di Fruscolo O, Sciruicchio V, et al. Efficacy of levetiracetam in Huntington disease. Clin Neuropharmacol. 2005;28:280–4.
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