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New AAN Guidelines for Treating Huntington's Chorea

Rukovets, Olga

doi: 10.1097/01.NT.0000417967.54902.a3


Chorea, an abnormal, involuntary movement disorder, is a classic feature of Huntington's disease (HD). Whether or not to prescribe drug treatment for chorea is an individual patient-doctor decision, but now the AAN has released a new guideline published online ahead of print on July 18 and in print on Aug. 7 in Neurology. The guideline provides insight on how to make this difficult choice and what effective pharmacologic options are available for adult HD patients.

The lead guideline author Melissa J. Armstrong, MD, who serves on the AAN Guideline Development Subcommittee, and coauthor Janis Miyasaki, MD, associate clinical director of the Movement Disorders Centre at Toronto Western Hospital of the University of Toronto, reviewed the existing literature through 2011. Dr. Armstrong, assistant professor of neurology at the University of Maryland School of Medicine, tells Neurology Today how to interpret the guidelines, what to keep in mind before prescribing any medications for chorea, and where more research is needed for HD-associated chorea.

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Evidence suggests that the drugs tetrabenazine, amantadine, and riluzole (all Level B) can be helpful and nabilone (Level C) may be helpful in treating chorea. While tetrabenazine is approved by the Food and Drug Administration (FDA) for the treatment of chorea in HD and is commonly used, the other drugs are not often prescribed for chorea in HD. Typical and atypical neuroleptics are often used clinically for HD chorea, but no high quality research was found to support this use of these drugs, and so the evidenced-based guideline could not make a recommendation regarding these treatments (Level U).



Also, the guideline identified that more research is needed to understand what change scores are clinically meaningful on chorea scales. It is possible that some of the improvements seen in studies of drugs for chorea were statistically significant but not clinically meaningful.

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The medications with the highest level of evidence in favor of use are tetrabenazine, amantadine, and riluzole 200mg/day, all of which received a Level B recommendation in cases where HD chorea requires treatment. Of these, however, tetrabenazine showed the most improvement on chorea scales. There was not enough data in the amantadine studies to know how much improvement one might expect; in fact, while patients described benefits, those improvements were not always captured on the chorea scales. Riluzole 200mg/day showed moderate improvement in chorea.

There was also Level B evidence against the use of riluzole 100mg/day, ethyl-EPA, minocycline, and coenzyme Q10 for HD chorea, though the precision in most of these studies was insufficient to rule out the possibility of small benefits.

There was Level C evidence that nabilone may result in modest decreases in chorea and there was Level C evidence against creatine use, at least for important changes in chorea. Data were insufficient to make recommendations regarding the use of neuroleptics or donepezil for HD chorea (Level U), though clinically neuroleptics are commonly used in HD.

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When considering serious side effects, the two most concerning possibilities with tetrabenazine are depression/suicidality and parkinsonism. Tetrabenazine may also prolong the corrected QT interval. Riluzole is associated with a risk of elevated liver enzymes. Nabilone is a synthetic cannabinoid that is listed by the FDA as a class two controlled substance with high abuse potential.

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The first step is to recognize that not all chorea requires treatment. HD is associated with a movement disorder (often chorea, at least at the beginning), cognitive impairment, and psychiatric problems. In some patients, the psychiatric and/or cognitive problems will cause much more disability than the motor problems and those need to be prioritized for treatment. Even when chorea is the main clinical symptom, not all HD patients require treatment for it. There is no good evidence regarding when to start medicine for chorea and the literature regarding whether improved chorea translates into less disability or functional decline or improved quality of life is conflicting. Patients and physicians must decide whether other HD symptoms require treatment more urgently than chorea.

When patients and physicians decide that chorea needs treatment, they need to individually weigh the options' risks and benefits. For example, tetrabenazine seems to have the most benefit for HD chorea and is the only FDA-approved treatment. It might not be a good choice for a patient with depression that is hard to control, though, given the risk of worsening depression/suicidality and potential interactions with select anti-depressants. While our evidence-based guideline could not find evidence to make a recommendation regarding neuroleptic use, a physician might decide to use a neuroleptic regardless, particularly if the patient has behavioral symptoms that require treatment and the hope is to try one drug that can theoretically address multiple symptoms.

Cost is also a concern — riluzole and nabilone, apart from other considerations, are likely to be prohibitively expensive for many HD patients.

It's important to discuss that the benefits of decreasing chorea are not completely clear; some studies report that improvements in chorea decrease disability or improve quality of life whereas other studies show no association between chorea and functional decline.

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When antichorea medication is initiated, long-term therapy is typically expected given HD's progressive nature. Most studies, though, are relatively short. Also, it was felt that the two riluzole studies — one lasting 8 weeks and one lasting 3 years — probably shouldn't be combined into a single analysis given different expectations for chorea change over those different time frames. Thus, we labeled studies conducted over a course of 12 months or less as “short-term” and studies lasting longer than 12 months as “long-term,” though the clinical significance of this division is unknown.

Of the medications for which a positive recommendation was made, tetrabenazine was studied over 12 weeks, amantadine was studied over 2 weeks, riluzole 200mg/day was studied over 8 weeks, and nabilone was studied over 5 weeks. Many of the long-term studies were aimed at non-motor objectives, such as neuroprotection, with chorea as a secondary endpoint. Thus, physicians are left making likely long-term chorea treatment decisions with primarily short-term data. While long-term treatment is generally expected, there may be occasions when short-term chorea reductions are desired (e.g., patients undergoing imaging studies or procedures or attending important events).

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It is critical for the clinically meaningful change for chorea scales to be studied. Without knowing what change in chorea is clinically important, it is difficult to interpret the results of chorea studies. Some studies may have results that are statistically significant but not clinically meaningful. From a treatment perspective, it would be helpful to have high quality studies examining the effect of neuroleptics on chorea and how this compares to other drugs. Better understanding of the effect of chorea treatments over long duration administration and across different HD stages is also important for guiding clinicians. And of course, HD remains a devastating neurodegenerative disease in need of neuroprotective treatments and treatments for other symptoms besides chorea.

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• Armstrong MJ, Miyasaki J Evidence-based Guideline: Pharmacologic treatment of chorea in Huntington's disease report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2012: E-pub 2012 Jul 18.
    ©2012 American Academy of Neurology