Short-term effects of tetrabenazine on chorea associated with Huntington's disease.
ABSTRACT We sought to assess the short-term clinical effects of tetrabenazine (TBZ) on choreic movements in Huntington's disease patients. A total of 10 patients on stable doses of TBZ were enrolled in this observational study. Patients took their evening dose of TBZ and presented the next day to the Baylor College of Medicine Movement Disorders Clinic without taking the usual morning dose. They were assessed using the Unified Huntington's Disease Rating Scale (UHDRS) motor assessment and Beck Depression Inventory. The usual morning dose of TBZ was then administered and patients were followed with serial UHDRS motor examinations approximately every 2 hours until choreic movements subsided and then returned. TBZ decreased the UHDRS chorea score on average 42.4% +/- 17.8%. The duration of effect varied from a minimum of 3.2 hours to a maximum of 8.1 hours (mean = 5.4 +/- 1.3). No patient experienced an adverse event related to TBZ or its withdrawal. During short-term follow-up after a single dose, TBZ improves chorea for approximately 5 hours.
Article: Treatment of Huntington's Disease.[Show abstract] [Hide abstract]
ABSTRACT: Huntington's disease (HD) is a dominantly inherited progressive neurological disease characterized by chorea, an involuntary brief movement that tends to flow between body regions. HD is typically diagnosed based on clinical findings in the setting of a family history and may be confirmed with genetic testing. Predictive testing is available to family members at risk, but only experienced clinicians should perform the counseling and testing. Multiple areas of the brain degenerate, mainly involving the neurotransmitters dopamine, glutamate, and γ-aminobutyric acid. Although pharmacotherapies theoretically target these neurotransmitters, few well-conducted trials for symptomatic interventions have yielded positive results and current treatments have focused on the motor aspects of HD. Tetrabenazine is a dopamine-depleting agent that may be one of the more effective agents for reducing chorea, although it has a risk of potentially serious adverse effects. Some newer neuroleptic agents, such as olanzapine and aripiprazole, may have adequate efficacy with a more favorable adverse effect profile than older neuroleptic agents for treating chorea and psychosis. There are no current treatments to change the course of HD, but education and symptomatic therapies can be effective tools for clinicians to use with patients and families affected by HD.Journal of the American Society for Experimental NeuroTherapeutics 12/2013; · 3.88 Impact Factor
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ABSTRACT: Basal ganglia are group of subcortical nuclei which are components of modular circuits involving cerebral cortex, thalamus and brain stem related with cortical functions. Basal ganglia includes four to five distinct loop which is responsible for parallel processing of information and grouped into two distinct direct and indirect pathways. Thus, this dual system provides a motor centre exhibiting both excitatory and inhibitory effect. These circuits are involved in movement disorders categorized as Hyperkinetic and Hypokinetic movement disorder. In recent year, with the upcoming studies it has been clear that functions of basal ganglia not only focuses motor disturbances but also involves cognitive and emotional functions as well.
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ABSTRACT: Chorea may contribute to balance problems and walking difficulties that lead to higher fall rates in individuals with Huntington’s disease (HD). Few studies have examined the effects of tetrabenazine (TBZ), an anti-choreic drug, on function and mobility in HD. The purpose of this study was to compare: 1) gait measures in forward walking, 2) balance and mobility measures, and 3) hand and forearm function measures on and off TBZ. We hypothesized that use of TBZ would improve gait, transfers and hand and forearm function. Eleven individuals with HD on stable doses of TBZ were evaluated while off medication and again following resumption of medication. Significant improvements were found on the Unified Huntington’s Disease Rating Scale (UHDRS) motor scores, Tinetti Mobility Test (TMT) total (t = 4.20, p = 0.002) and balance subscale (t = − 4.61, p = 0.001) scores, and the Five Times Sit-to-Stand test (5TSST, t = 3.20, p = .009) when on-TBZ compared to off-TBZ. Spatiotemporal gait measures, the Six Condition Romberg test, and UHDRS hand and forearm function items were not changed by TBZ use. Improved TMT and 5TSST performance when on drug indicates that TBZ use may improve balance and functional mobility in individuals with HD.Journal of the Neurological Sciences 10/2014; · 2.26 Impact Factor
Short-Term Effects of Tetrabenazine on Chorea Associated with
Christopher Kenney, MD, Christine Hunter, RN, Anthony Davidson, BS,
Joseph Jankovic, MD
Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology,
Baylor College of Medicine, Houston, Texas
OBJECTIVE: We sought to assess
the short-term clinical effects of
movements in Huntington disease
METHODS: A total of 10 patients on
stable doses of TBZ were enrolled in
this observational study. Patients
took their evening dose of TBZ and
presented the next day to the Baylor
College of Medicine
Disorders Clinic without taking the
usual morning dose. They were
Huntington Disease Rating Scale
(UHDRS) motor assessment and
Beck Depression Inventory (BDI).
The usual morning dose of TBZ was
then administered and patients were
followed with serial UHDRS motor
examinations approximately every 2
hours until choreic
subsided and then returned.
UHDRS chorea score on average
42.4 ± 17.8%. The duration of effect
varied from a minimum of 3.2 hours
to a maximum of 8.1 hours (mean =
5.4 ± 1.3). No patient experienced an
adverse event related to TBZ or its
CONCLUSIONS: During short-term
follow up after a single dose, TBZ
improves chorea for approximately 5
? To our knowledge, this is the
first report of short-term clinical
effects of TBZ
associated with HD.
?Clinical benefits at a given dose of
TBZ can be assessed rapidly in
?The mean duration of TBZ effect
on chorea equaled 5.4 ± 1.3 hours.
necessitates dosing three times per
day in most patients.
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Tetrabenazine treatment in movement disorders.
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treatment of hyperkinetic movement disorders.
Expert Rev Neurother 2006;6:7-17.
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antichorea therapy in Huntington disease: a
randomized controlled trial. Neurology
4. Frank S, Ondo WG, Hunter C, et al. A
randomized, double-blind, placebo-controlled,
staggered withdrawal study in patients with
Huntington's disease treated with tetrabenazine.
Ann Neurol 2006;(in press).
5. Ondo WG, Tintner R, Thomas M, et al.
Tetrabenazine treatment for Huntington's
disease-associated chorea. Clin Neuropharmacol
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tetrabenazine in hyperkinetic movement
disorders. Neurology 1997;48:358-362.
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treatment of severe pediatric chorea. Mov Disord
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Tetrabenazine-induced depletion of brain
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Tetrabenazine (TBZ), a monoamine-
depleting drug synthesized nearly 50
years ago, inhibits monoamine uptake
into granular vesicles of presynaptic
neurons through its ability to bind to
vesicular monoamine transporter 2
(VMAT2). Though initially designed as
an antipsychotic medication, clinicians
primarily use TBZ to treat a variety of
hyperkinetic movement disorders such
as chorea, tics, and tardive dyskinesia.
TBZ ameliorates chorea related to
Huntington disease (HD) and other
etiologies. In published clinical trials,
the dose of TBZ is usually titrated to
“best dose,” defined as the dose that
provides efficacy without intolerable
side effects. TBZ, however, displays
considerable inter-individual variability
with regard to “best dose”; some
patients respond to doses as low as
12.5 mg/day, whereas others require
up to 400 mg/day. For a given
individual, the therapeutic window for
TBZ is quite narrow. Dose-limiting
side effects include
? All patients met clinical criteria
for HD and were
disabled by chorea
? Stable TBZ
requirement for inclusion in the
? Patients took their last regular
dose of TBZ the evening prior to the
observation day. At least 12 hours
intervened between the last dose
and the baseline evaluation.
? One rater (CK) completed all
clinical evaluations. Baseline data
consisted of the motor portion of
the Unified Huntington Disease
Rating Scale (UHDRS) and the Beck
Depression Inventory (BDI).
? Each patient then took their
usual morning dose of TBZ followed
by serial assessments
UHDRS motor score every 90-150
minutes. A total of at least 4 serial
assessments were completed until
reemergence of baseline chorea
indicated wearing off of TBZ benefit.
? The maximal decrease in UHDRS
chorea score was calculated by the
dosing was a
Baseline UHDRS chorea score
– Lowest UHDRS chorea score
Baseline UHDRS chorea score
? Duration of effect was defined as
the time needed for the chorea
score of the
assessment to return to baseline
from the time of TBZ administration.
? To calculate duration of effect in
four patients whose chorea score
did not return to the baseline value,
the return-to-baseline time values
extrapolation of the final two time-
points relative to the baseline
UHDRS chorea score.
?The 10 patients (6 males) had a
mean age of 56.3 ± 11.6 years and a
mean duration of symptoms of 10.4
± 5.8 years (Table 1).
? Daily TBZ dosage ranged from
37.5 to 175.0 mg/day (mean = 90.0 ±
?The baseline UHDRS and BDI
scores were 54.7 ± 24.9 and 8.3 ±
?Based on the rated perceptual
intensity change of one rater, the
UHDRS chorea score decreased by
42.4% ± 17.8 with a tendency to
improve (decrease) and then worsen
?The mean duration of effect
equaled 5.4 ± 1.3 hours.
Table 1. Demographic Information
48F 45 37.5835
59M 10 42175.0 8410
62M941 75.057 15
67F14 4150.035 18
55F5 4337.5 194
95% CI/F itted v alues /UHDR S S c ore
0 100 200300400
Minutes Post TBZ Administration
UHDRS Chorea Scores Vs. Time (Minutes) After Administration of TBZ
Baseline = At Least 12 Hours Off TBZ
Minutes Post-TBZ Administration
U H D R S C h o r e a S c o r e