An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington’s Disease

Abstract

It is generally believed that treatments are available to manage chorea in Huntington’s disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews available chorea studies, and lastly presents an algorithm for the treatment of chorea in HD which is based on expert preferences obtained through this international survey.

Current Pharmacological Approaches to Reduce Chorea in Huntington’s Disease

“…Specialists start symptomatic treatment in HD in consultation with the patient and family when chorea is causing balance disturbances, falls, and physical injury, and when it interferes with daily functioning at work and at home [3, 10]. In a Europe-wide assessment of medication use among HD patients, 39.3% of all registered HD patients received medication for the treatment of chorea, comprising dopamine depleting drugs, antipsychotics, or antiparkinsonian medication [25].…”

“…Pharmacological treatment is therefore focused on improving daily functioning by reducing symptom severity [9, 10]. …”

“…To date, practice-based studies showed that among HD experts, there is a wide variety in preferred drugs to treat chorea [10, 11]. Non-pharmacological treatment approaches to reduce chorea are currently also under investigation.…”

Orphan drugs in development for Huntington's disease: challenges and progress

“…Until recently, few high-quality clinical trials had been performed specifically for the treatment of symptoms in HD patients, 69 and a wide range of drugs used, due to a lack of consensus. 70 Tetrabenazine was the first drug to be approved for symptomatic treatment in HD, in this case chorea. The drug inhibits the vesicular monoamine transporter (VMAT), and at doses up to 100 mg per day UHDRS chorea, 71 and improves global clinical impression, with a clear deterioration after withdrawal.…”

Recent advances in the management of choreas

“…Faced with the paucity of good evidence to prepare guidelines to treat movement disorder in HD [Bonelli and Hofmann, 2007;Bonelli and Wenning, 2006;Venuto et al 2012], we have performed a survey on the use of drugs to treat chorea in different continents [Burgunder et al 2011]. Survey results showed that patient's need, including stigma, physical injury, gait instability, work interference and disturbed sleep were indications to start antichoreic drugs, but there were profound differences in their choice.…”