Short-Term Effects of Tetrabenazine on Chorea Associated with Download full-text
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 (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 4537.5 83 5
59M1042 175.0 84 10
61M442 50.0 2412
95% CI/F itted v alues /UHDR S S c ore
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