Tetrabenazine Can Be Helpful in Chorea Associated With Huntington's Disease
PHILADELPHIA (Reuters Health) May 08 2001 - New findings presented here Tuesday at the 53rd annual meeting of
the American Academy of Neurology (AAN) suggest that tetrabenazine may be an effective and well-tolerated treatment for Huntington's
Dr. William G. Ondo and associates, from Baylor College of Medicine in Houston, Texas, reported
that blinded videotape assessment of motor scores showed an improvement in 12 of 15 patients following 7 months of tetrabenazine
treatment. Scores worsened in two patients and remained
unchanged in one patient. Except for one case of akathisia, side
effects were mild.
Participants in the trial were videotaped at the time of enrollment and then started on tetrabenazine
therapy at 12.5 mg/day. The dose was increased until a clinical effect was seen and patients were videotaped again 6 months
later. The videotapes were assessed by investigators who rated involuntary movements using the modified Abnormal Involuntary
Movement Scale (AIMS).
Subjects had a mean of 42.6 CAG repeats - triplet amino acid repeats that are characteristic
of Huntington's - and the number of repeats was not significantly different among the patients. The duration of symptoms of
Huntington's disease was 8.3 years. Eleven patients had tried a total of
19 medications chosen specifically for chorea
prior to enrollment.
Blinded AIMS scores improved from 17.0 to 13.5 after treatment with tetrabenazine. Patients (and
family, when applicable) rated the improvement as marked in four cases, moderate in four, mild in two,
and none in one.
Ondo emphasized that the study only evaluated chorea, and only in Huntington's disease patients for whom
it was a major feature of their disease. Chorea, he pointed out, represents only one feature of Huntington's disease and may
not be the major cause of disability. "The results should thus not be interpreted to mean that tetrabenazine helps all
Huntington's disease patients," he said.
Despite these and other limitations in the study design, Dr. Ondo said,
"we believe that this drug should be considered for patients with Huntington's disease-associated chorea given the fairly
consistent benefit and good tolerability shown in this study and the relatively poor efficacy of traditional treatments for
He added that the results concur with those of open-label and smaller partially controlled and controlled
Study-Clozapine non effective in HD
Clozapine versus placebo in Huntington's disease: a double blind randomised
J Neurol Neurosurg Psychiatry 1997 Jul;63(1):35-9 (ISSN: 0022-3050)
van Vugt JP; Siesling
S; Vergeer M; van der Velde EA; Roos RA Department of Neurology, Leiden University Medical Centre, The Netherlands.
establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability
in patients with
Thirty three patients with Huntington's disease
participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo
equivalent was given for
a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using
the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS),
and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale.
their partners completed a questionnaire regarding functional
disability. Twelve patients already used other neuroleptic
medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients
were analysed separately.
Clozapine tended to reduce chorea in neuroleptic naive patients
only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine.
Other measures of chorea (UHDRS chorea score, video ratings) showed
Clozapine had no beneficial effect on chorea in patients already receiving
Voluntary motor performance did not improve with clozapine.
Neuroleptic naive patients reported aggravation of functional
disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six
patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking
Clozapine has little beneficial effect in patients with Huntington's
although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often
encountered, clozapine should be used with restraint in this patient group.
First thing, for sudden increases in chorea movements is to check
what else might be causing them like being upset, tired, etc. Also check for reactions or combination with other
medications or over the counter stuff .
For more information go to FDA's CDER page
http://www.fda.gov/cder/consumerinfo/druginteractions.htm Drug Interactions and Over-the-Counter Medicines
Learning More About Drug Interactions
Examples of Drug Interaction Warnings
The PG to HD describes
some medications which have been used, but also recommend other considerations before medicating (see other page)
MOVEMENT DISORDER MEDICATIONS
Many of the drugs used to treat movement disorders are prescribed
for more than one disorder. Because of this, information about these drugs is located in a variety of places on the WE MOVE
web site. On this page, you can link to all of the pages that discuss each drug throughout the site.
Click on http://www.wemove.org/meds_pis.html to find following information on the package inserts for
Alprazolam (Xanax®) Package Insert
(Lioresal®) Package Insert
Botox® (Botulinum Toxin Type A) Package Insert - (41k pdf)
mesylate (Parlodel®) Package Insert
Carbamazepine (Tegretol®) Package Insert
(Sinemet®) Package Insert
Clonazepam (Klonopin®) Package Insert
Clonidine hydrochloride (Catapres®) Package Insert
Dantrium® (dantrolene sodium)
capsules Package Insert - (28k pdf)
Diazepam (Valium®) Package Insert
Myobloc-TM (Botulinum Toxin Type B) Package Insert
Oxycodone Hydrochloride (Percocet®)
Pergolide mesylate (Permax®) Package Insert
Pramipexole dihydrochloride (Mirapex®)
Risperidone (RisperdalT) Package Insert
Ropinirole hydrochloride (RequipT)
Temazepam (Restoril®) Package Insert
Tizanidine (Zanaflex®) Package
Triazolam (Halcion®) Package Insert
Valproate (Depakene®) Package Insert
on http://www.wemove.org/meds.html then on a drug name to see the pages where that drug is discussed (like
referenced studies, etc on medication with HD)
tizanidine OR Zanaflex
dantrolene OR dantrium
S49.005 A double-blind, placebo-controlled crossover study of the effect of amantadine on chorea in Huntington's disease L
Verhagen, M Morris, C Farmer, M Gillespie, J Wu, TN Chase
Amantadine is effective for chorea in HD, according to this
Twenty-two patients with HD received either placebo or 300-400 mg amantadine for two weeks, followed by crossover
to the other arm. Compared to baseline, treated patients had a 25% decrease in chorea at rest, versus 4% for placebo (p=0.01).
An 18% improvement was seen for
chorea during activity, versus 5% for placebo (p=0.01). Mean improvements reflect a varied
response among patients, in which approximately one third showed improvement of better than 50%, while several patients showed
little or no response.
father had tried Artane, made this falling down much worse and he was
unable to maintain his balance. So he is on
no medications at this time.
- Do NOT take for chorea
Also, young children on this medication may experience seizures "the psychiatrist
got a warning about the probability of children and youth having seizures while taking it. She immediately pulled
him off. "
Clozapine appears to be more active at the limbic dopamine receptors than at the striatal receptors and
does not induce parkinsonism or tardive dyskinesias. In addition, clozapine has been shown to treat some of the movement disorders
associated with PD (eg, tremor, dystonia, and dyskinesia) by a direct mechanism that is independent of the antipsychotic effect.
clozapine therapy has been associated with a potentially serious adverse effect, idiosyncratic agranulocytosis. As a result,
frequent blood counts are required for patients taking this medication. The primary dysfunction responsible for the
olanzapine-associated decline was
bradykinesia and gait.
Kelly took diazepam/valium which, although addictive does not have the
same concerns with Tardive
Dystonia or Neuroleptic Malignant Syndrome
associated with some of the other recommended medications.http://www.intelihealth.com/IH/ihtIH/WSIHW000/8271/8271.html?k=zonex408x8271===========================================================================
is primarily used for depression (and obsessive complusive disorders)
Herbal/dietary supplement products may interact
with this medication. Discuss any such product with your doctor or pharmacist before taking.
Single Fluoxetine Dose Improves Motor Skills Impaired by Stroke
YORK (Reuters Health) Dec 12 - One dose of fluoxetine modulates cerebral motor activation in patients with hemiplegia due
to lacunar infarcts. This activation correlates to an improvement of motor performance, French investigators report.
a prospective crossover study, Dr. Francois Chollet and associates at Hopital Purpan in Toulouse, France, evaluated 8 highly
selected patients after a pure motor stroke caused by a central lesion of the cortico-spinal tract. Each patient underwent
functional MRI at 7 to 23 days post-stroke and again 7 days later. The examinations were conducted once
5 hours after administration
of fluoxetine 20 mg, and the other time after administration of placebo.
During an active task of flexion-extension
of the fingers of the affected hand, fluoxetine compared with placebo caused greater activation of the signal from the ipsilesional
primary motor cortex, the investigators report in the Annals of Neurology for December.
Several areas became hypoactivated
by fluoxetine during the active task, including the cerebellum, the contralesional caudate nucleus, the contralateral inferior
premotor cortex, and the cingulum.
Fluoxetine exerted no effect during a passive task during which a clinician performed
flexion-extension of the affected wrist.
Patients treated with fluoxetine also performed significantly better during
a finger-tapping test and a dynamometer strength test than when treated with placebo. The French investigators attribute fluoxetine's
hyperactivation effect to stimulation through the serotonin system of
pyramidal cells, which are quite dense in the primary
Ann Neurol 2001;50:718-729.
(see other page)
increases choreatic movements in Huntington's disease
Mov Disord 1999 Nov;14(6):1038-40
Reports it was noticed when given to Phd's their movements also slowed down...
My husband participated in a trial that tested for tolerablity and
movements... it was a double blind test and he was on the real drug... It helped his chorea a great deal and he has continued
to be on it at a dose of 7.5 mg... any higher and he had a great deal of swelling... we are very happy with the results of
this drug. PatD
Since Olanzapine is currently prescribed for HD am assuming
the recommened trials have been
completed. Also see: Olanzapine
Brand name: Zyprexa http://www.mentalhealth.com/fr30.htmlThe use of olanzapine for movement disorder in Huntington's disease:
a first case report J Neurol Neurosurg Psychiatry 1999;67:123-124 ( July )
The mechanism by which olanzapine may have beneficial effects is
This case report indicates that olanzapine may be a useful addition to the treatments for movement disorder,
for some patients, and controlled trials of its use in Huntington's disease would be welcome
http://www.mentalhealth.com/drug/p30-o02.htmlPatients blood should be checked for elevated creatine phosphokinase
and other stuff to make sure they don't get the bad stuff;Neuroleptic Malignant Syndroms (NMS). A Medscape article on
this drug indicates NMS is one of the most significant adverse affects of this drug.
Smoking may reduce the active ingredients in Olanzapine by
to 60% Elderly or debilitated patients (late stage HD) should be monitored closely if on other drugs.
doctor of all prescription or nonprescription drugs you take, especially of: medicine for sleep, antidepressants, tranquilizers
(such as diazepam), narcotic pain medicines, Parkinson's disease or seizure medicines, high blood pressure drugs, antihistamines,
omeprazole, rifampin, anti- cholinergics (e.g., benztropine, hyoscyamine).
Since Olanzapine is
currently prescribed for HD am assuming
the recommened trials have been completed. Also see:
name: Zyprexa http://www.mentalhealth.com/fr30.html
The use of olanzapine for movement disorder in Huntington's disease:
a first case report
J Neurol Neurosurg Psychiatry 1999;67:123-124 ( July )
by which olanzapine may have beneficial effects is unclear. Olanzapine has been shown to have high affinity for a large number
of receptors including D1, D2, D4, 5HT2A, 5HT2C, 5 HT3, -1-adrenergic, histamine H1, and 5 muscarinic receptors.
binding profile is similar to clozapine, another atypical antipsychotic drug, but substantially different to the conventional
Preferential loss of D2 projection neurons which are involved in a feedback loop normally
active in the suppression of involuntary movements is thought to be the pathophysiological basis of chorea in patients with
Huntington's disease. The D2 antagonist properties of olanzapine may explain its possible benefits in the improvement
of chorea. However,
the effect at other receptors such as D4 may also be important, as D4 receptor density has been
shown to be raised in Huntington's disease, therefore the D4/D2 ratio of activity may also be relevant. Differences in binding
profile across a range of receptors may explain clinical differences in outcome when comparing different antipsychotic drugs.
case report indicates that olanzapine may be a useful addition to the treatments for movement disorder, for some patients,
and controlled trials of its use in Huntington's disease would be welcome
Full study available at JNNP OnLine
All family experiences:
do NOT take in HD can have severe consequences.
Subject: Tetrabenazine for Huntington's Disease (AAN 2001)
5/8/01 http://www.wemove.org/emove/article.asp?ID=319E-MOVE reports from the 53rd Annual Meeting of the American Academy
of Neurology in Philadelphia May 5-11, 2001. Poster and Platform session numbers refer to abstracts published in Neurology
2001;56 (Supplement 3).
P01.012 Tetrabenazine for Huntington's disease chorea: A single-blind study WG Ondo, R Tintner,
C Kwak, M Thomas, J Jankovic
Tetrabenazine can improve chorea in HD for up to a year, according to this study. Twelve
patients (mean age 58) received tetrabenazine for 4-12 months (mean dose 66 mg/day).
Abnormal Involuntary Movement
Scale scores rated by a blinded investigator decreased from 17.0 to 13.5 (p=0.02). Other features of the disorder were not
Adverse effects included akathisia, constipation, drooling, and insomnia, most of which resolved with dose
Reported December 2001
ROCHESTER, N.Y. (Ivanhoe Newswire)
- Standard treatment for Parkinson's disease is the drug levodopa. However, the drug brings with it a host of side effects
including involuntary hand, arm and leg movements. Now, doctors say a new drug may be an effective treatment for Parkinson's
patients with fewer side effects.
A recent study shows a new drug, pramipexole, also called Mirapex,
may reduce the side effects of levodopa. Doctors say combine the two drugs and patients may have better disease control with
fewer unwanted side effects.
Neurologist Robert Holloway, M.D., of the University of Rochester, is encouraged. "If
you initiate a therapy with pramipexole, there is approximately a 50 percent reduction in the occurrence of these complications
over a two year period," he says.
Dr. Holloway says each patient should be assessed individually to determine which
therapy would work best for him or her. Side effects of pramipexole may include sudden sleepiness, hallucinations and
swelling of the ankles, feet or legs.
I found this interesting, but particularily the reference to the
between chorea and women taking oral contraceptives. When Kelly was first suspected of having HD she
found a medical book in her school library which said in rare cases, some females who have taken oral contraceptives have
gotten HD after having an abortion. Kelly had been on oral contraceptives for about a year, went off them, got
pregnant and had an abortion. Since we weren't aware of HD in either side of her family, I honestly thought this is
what happened with Kelly.
Years later, when talking to a doctor at USF I had asked him about
this possible relationship and he looked at me like I had just escaped from the funnyfarm. When I brought the xerox
copy of that article in to him later, he just went "hmmmmmmm" and kept it.
Perhaps that article (1983 timeframe) was
preliminary research into oral
contraceptives and chorea?
Does this mean that women who have HD, or are at risk
for HD, should not be taking oral contraceptives? Has any female with HD's chorea symptoms been advised not to take
Just a thot.
From the Merck
http://www.merck.com/pubs/mmanual/section14/chapter179/179c.htmCHOREA AND ATHETOSIS
is brief, purposeless involuntary movements of the distal extremities and face, which may merge imperceptibly into purposeful
or semipurposeful acts that mask the involuntary motion. Athetosis is writhing movements, often with alternating postures
of the proximal limbs that blend continuously into a flowing stream of movement.
(See also Sydenham's Chorea in Ch.
Chorea and athetosis often occur together (choreoathetosis). The most important cause of chorea is Huntington's
disease (see below). Other causes include thyrotoxicosis, SLE affecting the CNS, and drugs (eg, antipsychotics).
Chorea and athetosis are manifestations of dopaminergic overactivity
in the basal ganglia--the antithesis of Parkinson's disease. The role of cholinergic and other systems is less clear in the
pathophysiology of the dyskinesias than in that of Parkinson's disease.
Chorea gravidarum is choreiform
movement occurring during pregnancy, often in patients with a history of rheumatic fever. Chorea usually begins during the
first trimester and resolves spontaneously by or after delivery.
Rarely, a similar disorder occurs in women taking oral contraceptives.
Treatment consists of sedation with barbiturates, because other drugs may harm the fetus.
is violent, continuous proximal limb flinging movements confined to one side of the body, usually affecting the arm more than
the leg. It is caused by a lesion, usually an infarct, in the region of the contralateral subthalamic nucleus of Luys. Differential
diagnosis includes acute hemichorea, usually due to tumor or infarct of the caudate nucleus,
and focal seizures. Although
disabling, hemiballismus is usually self-limited, lasting 6 to 8 wk. Treatment with antipsychotics is often effective.