Tetrabenazine for Moderate vs. Severe/Disabling Chorea Associated with Huntington's Disease (HD) (P06.032)

Objective: To assess dosing, efficacy, and safety of tetrabenazine for patients with moderate vs. severe/disabling HD-chorea. Background At study initiation (1979), tetrabenazine had not yet been approved in the US (2008). Design/Methods: In an open-label study, patients with hyperkinetic movement disorders were evaluated at Baylor College of Medicine. Tetrabenazine was used “last resort,” when other medications failed to provide satisfactory control. For HD-chorea patients, all previous chorea treatments were discontinued before tetrabenazine initiation. Patients were initially hospitalized, and tetrabenazine was started at 12.5 mg/day (≤300 mg/day maximum). Dosage was increased every 3 days, until a dosage-limiting AE occurred, and then down-titrated to greatest tolerated dosage. Visits were 6 weeks after hospitalization, and every 3 months thereafter. Responses were rated on a scale of 1–5 (1 = marked chorea reduction, excellent improvement in function; 2 = moderate chorea reduction, very good improvement in function; 3 = fair chorea improvement, only mild improvement in function; 4 = poor/no response for chorea/function; 5 = worsening chorea/some functional deterioration). 1 Results: By 2004, 98 HD-chorea patients had participated. At baseline, 44 had moderate and 54 had severe/disabling chorea. 45% with moderate vs. 61% with severe/disabling chorea received tetrabenazine >2 years. Average daily dosages (SD; range of mean dosages) were 60.5 mg (25.9; 16.9–138.1) and 74.8 mg (45.0; 21.4–225.5) for moderate and severe/disabling chorea, respectively. On optimal dosages, 71% of moderate chorea patients achieved a marked or very good rating (any time point) vs. 78% for severe/disabling. Five most common AEs (moderate, severe/disabling) were somnolence (43%, 22%), insomnia (16%, 15%), depression (23%, 11%), akathisia (7%, 15%), and nervousness (7%, 13%). Conclusions: Tetrabenazine dosing is highly individualized, independent of chorea severity. Responses to tetrabenazine and AE rates were similar for patients grouped by chorea severity. 1 Jankovic J, et al. Neurology . 1988;38:391–4. Supported by: Lundbeck Inc. Disclosure: Dr. Shen has received personal compensation for activities with Lundbeck Inc as an employee. Dr. Clarence-Smith has received personal compensation for activities with Lundbeck Research USA, Inc. Dr. Hunter has received personal compensation for activities with Lundbeck Research USA, Inc. as a consultant. Dr. Jankovic has received personal compensation for activities with Allergan, Inc., Chelsea Therapeutics, Serono Inc., Merz Pharma, Lundbeck Research USA, Inc, Teva Neuroscience as a consultant. Dr. Jankovic has received personal compensation in an editorial capacity for Medlink: Neurology in Clinical Practice. Dr. Jankovic has received research support from Allergan, Inc, Allon Therapeutics, Ceregene, Inc., Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation, Serono Inc., Huntington9s Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Research USA, Inc.