AAN Summary of Evidence-based Guideline for CLINICIANS

Pharmacologic Treatment of Chorea

in Huntingtons Disease

This is a summary of the American Academy of Neurology (AAN) guideline regarding pharmacologic treatment of chorea in
Huntingtons disease (HD).
Please refer to the full guideline at www.aan.com for more information, including definitions of the classifications of evidence
and recommendations.

Drug Warnings

The following treatments have associated US Food and Drug Administration (FDA) warnings:
Nabilone (Cesamet): http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf
Riluzole (Rilutek): http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020599s013lbl.pdf
Tetrabenazine (Xenazine): http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021894s004lbl.pdf
For adult patients with HD requiring symptomatic chorea therapy, what available pharmacologic agents effectively reduce chorea as
measured by validated scales?

Dopamine-modifying Drugs
Moderate evidence

If HD chorea requires treatment, clinicians should prescribe tetrabenazine (TBZ) (up to 100 mg/day) (Level B).
Clinicians should discuss possible adverse effects (AEs) with patients with HD and monitor for their occurrence.
TBZ likely has very important antichoreic benefits. Clinicians should discuss possible AEs with patients with HD and
monitor for their occurrence, particularly parkinsonism and depression/suicidality with TBZ.

Insufficient evidence

Data are insufficient to make recommendations regarding use of clozapine or other neuroleptics for HD chorea
treatment (Level U).

Glutamatergic-modifying Drugs
Moderate evidence

If HD chorea requires treatment, clinicians should prescribe amantadine (300400 mg/day) or riluzole (200 mg/day)
(Level B). Clinicians should discuss possible AEs with patients with HD and monitor for their occurrence, particularly
elevated liver enzymes with riluzole.
Riluzole 200 mg/day likely has moderate antichoreic benefits (Level B).

Insufficient evidence

The degree of benefit for amantadine is unknown (Level U).

Moderate evidence

Whereas riluzole 200 mg/day likely decreases chorea, clinicians should not prescribe riluzole 100 mg/day for
moderate short-term benefits (Level B negative) or for any long-term (3-year) HD antichoreic goals (Level B negative).
Modest short-term benefits of riluzole 100 mg/day cannot be excluded.

Energy Metabolites
Moderate evidence

Clinicians may choose not to prescribe ethyl-EPA for very important improvements in HD chorea (Level B negative).
Moderate antichoreic benefits cannot be excluded.

Weak evidence

Clinicians may choose not to prescribe creatine for very important improvements in HD chorea (Level C negative).
Moderate antichoreic benefits cannot be excluded.

Other Therapies
Weak evidence

Clinicians may prescribe nabilone for modest decreases in HD chorea (Level C).

Insufficient evidence

Information is insufficient to recommend long-term use of nabilone, particularly given abuse potential concerns (Level U).
Data are insufficient to make recommendations regarding use of donepezil for HD chorea treatment (Level U).

Moderate evidence

Clinicians may choose not to prescribe minocycline for very important improvements in HD chorea (Level B negative).
Moderate antichoreic benefits cannot be excluded.
Clinicians may choose not to prescribe coenzyme Q10 for moderate improvements in HD chorea (Level B negative).
Modest antichoreic benefits cannot be excluded.

Clinical Context

TBZ is the only US Food and Drug Administration (FDA)-approved drug for treating HD chorea, and thus other drug options are off-label. HD
studies typically enroll patients who are ambulatory, retain good functional capacity, and are free from disabling depression or cognitive decline.
Thus, study results may not apply to the entire HD population. Additionally, the clinically meaningful change for United Huntington Disease
Rating Scale (UHDRS) chorea is not established. We ranked degree of benefit using an effect size of 1.0, but the clinical relevance of this grading
system is unknown. In addition, short-term and long-term designations may or may not be meaningful. Results demonstrated over specific
study durations may not apply to other time frames.
Physicians and patients must consider individually whether chorea requires treatment. Some studies report that improvements in chorea decrease
disability or improve quality of life; other studies show no association between chorea and functional decline. Preferences of patients with HD
for symptomatic therapy are unstudied, highlighting the importance of individualized decisions. In decision making about whether to treat
chorea, other issues, including mood disturbance, cognitive decline, and AE and polypharmacy risks, should be considered. Cost and availability
are also important; TBZ, riluzole, and nabilone can be prohibitively expensive. Nabilone also is a class two controlled substance with high abuse
potential, so longer-term studies are required.
Neuroleptic agents are traditionally used for HD chorea treatment, and neuroleptics and antidepressants are the most commonly prescribed
drugs in HD. Other than the clozapine study, only two studies of neuroleptic treatment for HD chorea had sufficient sample size for
consideration. Both examined tiapride, an atypical neuroleptic unavailable in North America, but neither used validated outcome measures.
Neuroleptic agents may be reasonable options given behavioral concerns in HD and historical suggestion of antichoreic benefit, but formal
guidelines cannot be provided. Additionally, neuroleptic AEs require consideration, particularly parkinsonism.
Given prevalence of depression and suicide in HD, clinicians should screen for these before and during TBZ use, and should monitor for signs
of parkinsonism. EKG changes were not observed in HD TBZ studies, but pretreatment EKGs are reasonable. TBZ prescribing information in
the United States recommends genotyping for CYP2D6, the enzyme responsible for metabolizing TBZ, prior to TBZ use. Whether this advice
is followed clinically is unknown. Possible interactions with other medications metabolized by the CYP2D6 system, such as fluoxetine or
paroxetine, should be considered during TBZ dosing.
The significance of conflicting findings for different doses and treatment durations of riluzole is unknown. It is possible that 200 mg/day is the
minimum dose needed for antichoreic effect. There is insufficient evidence to conclude whether patients unable to tolerate 200 mg/day should
continue riluzole at the 100-mg dose.

This is an educational service of the American Academy of Neurology. It is designed to provide members with evidence-based guideline recommendations to
assist the decision making in patient care. It is based on an assessment of current scientific and clinical information and is not intended to exclude any reasonable
alternative methodologies. The AAN recognizes that specific patient care decisions are the prerogative of the patient and the physician caring for the patient,
and are based on the circumstances involved. Physicians are encouraged to carefully review the full AAN guidelines so they understand all recommendations
associated with care of these patients.

2012 American Academy of Neurology

Copies of this summary and additional companion

tools are available at www.aan.com or through
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www.aan.com (800) 879-1960