Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators

Abstract

BackgroundTetrabenazine (TBZ) selectively depletes central monoamines by reversibly binding to the type-2 vesicular monoamine transporter. A previous double blind study in Huntington disease (HD) demonstrated that TBZ effectively suppressed chorea, with a favorable short-term safety profile (Neurology 2006;66:366-372). The objective of this study was to assess the long-term safety and effectiveness of TBZ for chorea in HD.MethodsSubjects who completed the 13-week, double blind protocol were invited to participate in this open label extension study for up to 80 weeks. Subjects were titrated to the best individual dose or a maximum of 200 mg/day. Chorea was assessed using the Total Maximal Chorea (TMC) score from the Unified Huntington Disease Rating Scale.ResultsOf the 75 participants, 45 subjects completed 80 weeks. Three participants terminated due to adverse events (AEs) including depression, delusions with associated previous suicidal behavior, and vocal tics. One subject died due to breast cancer. The other 26 subjects chose not to continue on with each ensuing extension for various reasons. When mild and unrelated AEs were excluded, the most commonly reported AEs (number of subjects) were sedation/somnolence (18), depressed mood (17), anxiety (13), insomnia (10), and akathisia (9). Parkinsonism and dysphagia scores were significantly increased at week 80 compared to baseline. At week 80, chorea had significantly improved from baseline with a mean reduction in the TMC score of 4.6 (SD 5.5) units. The mean dosage at week 80 was 63.4 mg (range 12.5-175 mg).ConclusionsTBZ effectively suppresses HD-related chorea for up to 80 weeks. Patients treated chronically with TBZ should be monitored for parkinsonism, dysphagia and other side effects including sleep disturbance, depression, anxiety, and akathisia.Trial RegistrationClinicaltrials.gov registration number (initial study): NCT00219804

Treatment of Huntington's Disease

“…Compared with baseline, TBZ treatment resulted in a reduction of 5.0 Unified Huntington Disease Rating Scale (UHDRS) total maximal chorea units compared with a reduction of 1.5 units in the placebo group. There is also evidence to suggest continuous long-term efficacy and tolerability of TBZ in patients with HD [69][70][71][72].…”

Disease stage, but not sex, predicts depression and psychological distress in Huntington's disease: A European population study

“…We also included a number of other variables so we could control for several known predictors of depression and anxiety. These included: years in education, as a longer period in education has been found to be related to 9 lower levels of depression in later life [35]; certain medications (antidepressants, anxiolytics, mood stabilisers/anti-epileptics, neuroleptics, sleeping tablets, betablockers and tetrabenazine, the latter of which can have side-effects of anxiety and depression [36]); past use of antidepressants and anxiolytics, and history of depression (no assessment of history of anxiety is included in REGISTRY); cigarette use (number per day) and alcohol use (units per day), as these have both been found to affect depression and anxiety [37][38][39]; largest CAG repeat length and the Total Motor Score from the UHDRS (a composite measure of different motor tasks, including oculomotor function, dysarthria, chorea, dystonia, gait and postural stability, with higher scores indicating more motor impairment).…”

Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

“…Tetrabenazine was approved in 2008 by the United States Food and Drug Agency to control the involuntary periodic movements of the limbs and face, associated with chorea [34] . Tetrabenazine is a central monoamine extinguisher that reversibly binds to the type-2 vesicular monoamine transporter [35] . Dopamine and glutamate transmission and interaction are one of the affected pathway in the HD brain.…”