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Effect of tetrabenazine on computerized dynamic posturography in Huntington disease patients.

ABSTRACT: Impairment in computerized dynamic posturography scores has been documented in Huntington disease patients. Tetrabenazine is approved to treat chorea in Huntington disease, but its effect on posturography scores, and balance in general, is unknown.We designed a study to test computerized dynamic posturography performance while taking tetrabenazine and after stopping tetrabenazine for at least three days.10 Huntington disease patients were studied both ON and OFF tetrabenazine. The composite score was statistically different between ON and OFF conditions and both conditions were significantly worse than reference scores. There was no significant difference between ON and OFF trials in the number of falls. A significant improvement on sensory orientation test conditions 3 (sway-referenced vision) and 5 (sway-referenced motion of the support surface and eyes closed) was seen while ON tetrabenazine. Strategy scores 1-3 were also significantly different while ON tetrabenazine.These findings suggest that tetrabenazine aided patients in gating out of abnormal visual cues when other sensory modalities were available, as well as in gating out abnormal kinesthetic cues when visual cues were not available. It could not help with gating out of simultaneous abnormal visual and somatosensory cues. Thus, tetrabenazine can improve postural stability when one sensory modality is irrelevant, but this effect is not sustained when multiple abnormal sensory modalities are present. This is the first study supporting the use of any medicine to treat balance problems in Huntington disease.

SUBMITTER: Fekete R

PROVIDER: S-EPMC3424328 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Effect of tetrabenazine on computerized dynamic posturography in Huntington disease patients.

Fekete Robert R Davidson Anthony A Ondo William G WG Cohen Helen S HS

Parkinsonism & related disorders 20120522 7

<h4>Background</h4>Impairment in computerized dynamic posturography scores has been documented in Huntington disease patients. Tetrabenazine is approved to treat chorea in Huntington disease, but its effect on posturography scores, and balance in general, is unknown.<h4>Materials and methods</h4>We designed a study to test computerized dynamic posturography performance while taking tetrabenazine and after stopping tetrabenazine for at least three days.<h4>Results</h4>10 Huntington disease patien ...[more]

PMID: 22621818

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Project description:BackgroundVesicular monoamine transporter 2 (VMAT2) inhibitors can improve hyperkinetic movements, and are effective treatment options for chorea of Huntington disease (HD). Tetrabenazine was assessed for treating chorea in the TETRA-HD trial, and while efficacious, there are tolerability concerns possibly due to its pharmacokinetic properties. Deutetrabenazine is a novel VMAT2 inhibitor that contains deuterium, which extends active metabolite half-lives and minimizes drug concentration fluctuations. In the First-HD trial, deutetrabenazine was efficacious in treating chorea and was generally well tolerated. In the absence of a head-to-head trial, we performed an indirect treatment comparison (ITC) of the tolerability of deutetrabenazine and tetrabenazine for the treatment of HD-associated chorea, as observed in the First-HD and TETRA-HD trials, using well-established comparison methods.MethodsData from the Phase III, 12-week, parallel-group, clinical trials First-HD (N = 90) and TETRA-HD (N = 84) were used to conduct an ITC of the tolerability of deutetrabenazine versus tetrabenazine using two anchor-based methods: Bucher comparison for unadjusted ITCs, and matching indirect comparison for adjusted ITCs. Overall adverse events (AEs; mild, moderate, and severe), serious AEs, specific AEs occurring in ≥10% of patients, and discontinuations (all-cause and AE-related) were included in the analysis. The risk differences of these outcomes for deutetrabenazine and tetrabenazine were estimated by subtracting the applicable placebo-adjusted risk in First-HD from that of TETRA-HD. Sensitivity analyses were performed to address differences between trials, and p-values were obtained from z-tests.ResultsCompared with tetrabenazine, deutetrabenazine was associated with a significantly lower risk of moderate to severe AEs and neuropsychiatric AEs including agitation, akathisia, depression, depression/agitated depression, drowsiness/somnolence, insomnia, and parkinsonism in both adjusted and unadjusted analyses (p < 0.05 for each). Deutetrabenazine had a significantly lower rate of dose reduction or dose reduction/suspension in the unadjusted and adjusted analyses (p < 0.001 for each). Deutetrabenazine resulted in numerically more mild AEs, such as diarrhea and coughing; however, these results were not statistically significant.ConclusionsThis indirect treatment comparison demonstrates that for the treatment of HD chorea, deutetrabenazine has a favorable tolerability profile compared to tetrabenazine.Trial registrationClinicalTrials.gov NCT01795859 and NCT00219804.

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Effect of tetrabenazine on computerized dynamic posturography in Huntington disease patients.

Publications

Effect of tetrabenazine on computerized dynamic posturography in Huntington disease patients.

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