The prestigious American Academy of Neurology (AAN) has published a new set of "evidence-based" guidelines for the treatment of chorea in Huntington's disease (HD). These guidelines are based on "best evidence", which uses only sets of data from clinical trials or studies testing drugs for chorea. But what if there isn't enough evidence to make sound medical recommendations -- which had been the conclusion drawn by the Cochrane Review and the survey of expert HD physician leaders from the European Huntington's Disease Network (EHDN) and the Huntington Study Group (HSG)?

Why be concerned about the AAN guidelines? At best they are inappropriate; at worst they have potential to harm.

What are the AAN guidelines and what are the potential problems?

For the sake of brevity, a shortened key-word version of the AAN recommendations (noted in QUOTES) is taken from the abstract of the article. What follows is the author's opinion. I'm quoting from the abstract (though the entire article is open access to the public) because the abstract will be what most families and many community doctors see [Armstrong MJ 2012].

  1. "Clinicians should prescribe tetrabenazine, or amantadine" The problem is the word should because it does not address the complexity of prescribing for chorea in HD patients who have other symptoms. The AAN tetrabenazine (TBZ) recommendation was based on a single clinical trial that showed chorea benefit in participants specifically selected because they had no uncontrolled behavioral or psychiatric symptoms [Huntington Study Group 2006]. So participants in the trial were not characteristic of many "real world" patients who do have multiple symptoms -- where TBZ should probably not be prescribed prior to satisfactory treatment of other symptoms. Authors from a recent Cochrane review came to a different conclusion: even though TBZ had the best evidence, it wasn't sufficient to make a treatment recommendation [Mestre T 2009]. Regarding amatadine: Using information obtained from a survey, this drug is used by a minority of HD physician leaders from EHDN and HSG, while an equal number believed it may be harmful [Burgunder JM 2011].
  2. "Clinicians may prescribe nabilone" Not a single physician leader considered this drug a treatment for chorea. And any physician trying to prescribe it would have difficulty because insurers will not cover this very expensive drug that is prescribed for nausea and weight loss of cancer or AIDS.
  3. "Clinicians may choose not to prescribe ethyl-EPA, coenzyme Q-10 or creatine" Though not very useful, this makes sense.
  4. "Data are insufficient to recommend neuroleptics" This AAN guideline statement isn't just confusing, it is misleading. It's true that no quality clinical trials have been done testing neuroleptics or antipsychotics (therefore no evidence base) nor any completed trial that has compared TBZ to antipsychotics (though one is underway in Europe). The wording of the AAN statement can be confused with a "not recommend" using neuroleptics. Further, AAN neglected to point out that this recommendation contradicts the practice patterns of experienced EHDN and HSG HD physician leaders -- who in fact prescribe antipsychotic medications more frequently than tetrabenzine for chorea [Burgunder JM 2011].

So why the concern? The laudable AAN goal of making clinical recommendations based on "best evidence" is seriously flawed -- as has long been recognized [Feinstein AR 1997] -- by trying to make recommendations based on the inadequate quantity and quality of available evidence. This flaw has led to inappropriate and potentially harmful guidelines, that can only be amplified by the authoritative nature of AAN. Let's hope they reconsider.

My recommendations? For families: put your trust in HD physician leaders, not the AAN guidelines -- realizing that subsequent clinical trial evidence may (and should) change practice patterns. For physician leaders, the AAN guidelines tell us we should be working on improving the HD evidence base. And lastly, we look forward to results from the drug comparison study in France of tetrabenzine to olanzapine (Zyprexa®) and Tiapride, a neuroleptic drug prescribed frequently in Europe, but not available in the U.S.


Armstrong MJ, Miyasaki JM; American Academy of Neurology. Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2012 Aug 7;79(6):597-603. doi: 10.1212/WNL.0b013e318263c443. Epub 2012 Jul 18. PubMed abstract

Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006 Feb 14;66(3):366-72. PubMed abstract

Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington's disease. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD006456. doi: 10.1002/14651858.CD006456.pub2. PubMed abstract

Burgunder JM, Guttman M, Perlman S, Goodman N, van Kammen DP, Goodman L. An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington's Disease. Version 2. PLoS Curr. 2011 Aug 30 [revised 2011 Oct 11];3:RRN1260. PubMed abstract

Feinstein AR, Horwitz RI. Problems in the "evidence" of "evidence-based medicine". Am J Med. 1997 Dec;103(6):529-35. PubMed abstract