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Guideline Proposal for Treatment of Chorea in Huntington’s Disease
Melissa J. Armstrong, MD
Janis Miyasaki, MD
There are current no management guidelines for the treatment of Huntington’s disease (HD), a
progressive neurodegenerative disorder without cure. The prevalence of the condition has been difficult
to estimate historically given related stigma and lack of diagnostic confirmation, but with the advent of
genetic testing and greater insights into the disease, a 2010 report suggests that the prevalence may be
approximately 10.6 per 100,000 in Northern Ireland (Morrison 2010). Prior studies showed a prevalence
of 4-8 per 100,000 in most European countries (Frank 2010); North American data were not reported.
Chorea is a hallmark of HD along with cognitive decline and psychiatric impairment. While studies of
neuroprotection, cognitive therapies, and psychiatric therapies are still in their infancy in the HD
population, studies of treatment for chorea have been increasing over recent years. Pharmacotherapy
for chorea is important as chorea in HD can affect safety (difficulty positioning patients or injury can
result from the large amplitude movements) (Frank 2010), is associated with weight loss (Mahant,
McCusker et al. 2003), and is one of several factors in HD that can contribute to falls (Grimbergen, Knol
et al. 2008).
The proposed question for the guideline is: For HD patients requiring symptomatic therapy for chorea,
what treatments are effective in reducing chorea (as measured by validated scales) and what are the
associated adverse events with those treatments?
This topic will be of particular interest to neurologists practising within the field of movement disorders
but will also be relevant to the general neurologist trying to treat HD patients without access to
subspecialty centers. Because there is no consensus on appropriate management of chorea in HD, and
because the field has been increasing in recent years, a guideline will help evaluate the state of the
current evidence, highlight if one treatment is best supported, identify related risks, and reveal if
additional trials need to be performed.
The Cochrane Collaboration performed a review of 22 randomized controlled trials through December
2007, concluding that tetrabenazine was the drug with the best quality evidence for use but that no
intervention resulted in consistent benefit (Mestre, Ferreira et al. 2009). A brief Medline search (January
2010) shows that there are now 55 randomized controlled-trials found for English language studies of
drug therapy for chorea in HD (see Appendix for select examples). While not all of these studies are
likely relevant, the number suggests that there will be adequate articles for making recommendations
about appropriate treatment, particularly if non-English language studies are also included and EMBASE
is also searched. Furthermore, while the FDA has recently approved tetrabenazine for the treatment of
chorea in HD, this does not necessarily mean it is the treatment of choice. Tetrabenazine has known
adverse effects of parkinsonism and worsened depression that could be particularly problematic in the
HD population where these symptoms may already coexist. Thus, a systematic evaluation of adverse
effects will be critical in addition to a study of treatment benefits.
Particularly in a disease where there is a history of physicians and medical publications harming a
patient population as there is with early research in HD (Wexler 2010), the medical community has a
responsibility to promote high-quality research and care. By establishing guidelines for appropriate HD
treatment, we can improve the care of this challenging patient group and highlight where further
research is warranted.
References:
Frank, S. (2010). "Tetrabenazine: the first approved drug for the treatment of chorea in US patients with
Huntington disease." Neuropsychiatr Dis Treat 6: 657-65.
Grimbergen, Y. A. M., M. J. Knol, et al. (2008). "Falls and gait disturbances in Huntington's disease."
Movement.Disord. 23(7): 970-976.
Mahant, N., E. A. McCusker, et al. (2003). "Huntington's disease - Clinical correlates of disability and
progression." Neurology 61(8): 1085-1092.
Mestre, T., J. Ferreira, et al. (2009). "Therapeutic interventions for symptomatic treatment in
Huntington's disease." Cochrane Database Syst Rev(3): CD006456.
Morrison, P. J. (2010). "Accurate prevalence and uptake of testing for Huntington's disease." Lancet
Neurol 9(12): 1147.
Wexler, A. (2010). "Stigma, history, and Huntington's disease." Lancet 376(9734): 18-9.
Appendix: Sample References
- Brusa, L., A. Orlacchio, et al. (2009). "Treatment of the symptoms of Huntington's disease: Preliminary
results comparing aripiprazole and tetrabenazine." Movement Disorders 24 (1): 126-129.
- Dorsey, E. R. (2008). "Randomized controlled trial of ethyl-eicosapentaenoic acid in huntington disease
the TREND-HD study." Archives of Neurology 65 (12): 1582-1589.
- Frank, S. (2009). "Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label
continuation study. Huntington Study Group/TETRA-HD Investigators." BMC Neurology 9: 62.
- Kieburtz, K., M. P. McDermott, et al (2010). "A randomized, placebo-controlled trial of latrepirdine in
Huntington disease." Archives of Neurology 67 (2): 154-160.
- Lundin, A., E. Dietrichs, et al (2010). "Efficacy and safety of the dopaminergic stabilizer pridopidine
(ACR16) in patients with Huntington's disease." Clinical Neuropharmacology 33 (5):260-4.
- Marshall, F. J. (2006). "Tetrabenazine as antichorea therapy in Huntington disease: A randomized
controlled trial." Neurology 66 (3): 366-372.