Movement Disorder Medicines

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 disease-associated chorea.

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.

Dr. 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 this condition.

He added that the results concur with those of open-label and smaller partially controlled and controlled trials.

Medscape

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Study-Clozapine non effective in HD

July 2001

Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study.
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.

OBJECTIVES:
To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with
Huntington's disease.

METHODS:
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.

Patients and 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.

RESULTS:
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 no improvement.

Clozapine had no beneficial effect on chorea in patients already receiving
neuroleptic medication. 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 difficulties.

CONCLUSIONS:
Clozapine has little beneficial effect in patients with Huntington's disease,
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.

Source: Medscape

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MOVEMENT DISORDERS

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)
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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
Baclofen (Lioresal®) Package Insert
Botox® (Botulinum Toxin Type A) Package Insert - (41k pdf)
Bromocriptine mesylate (Parlodel®) Package Insert
Carbamazepine (Tegretol®) Package Insert
Carbidopa/levodopa (Sinemet®) Package Insert
Clonazepam (Klonopin®) Package Insert
Clonazepam (Rivotril®) Package Insert
Clonidine hydrochloride (Catapres®) Package Insert
Dantrium® (dantrolene sodium) capsules Package Insert - (28k pdf)
Diazepam (Valium®) Package Insert
Gabapentin (Neurontin®) Package Insert
Myobloc-TM (Botulinum Toxin Type B) Package Insert
Oxycodone Hydrochloride (Percocet®) Package Insert
Pergolide mesylate (Permax®) Package Insert
Pramipexole dihydrochloride (Mirapex®) Package Insert
Risperidone (RisperdalT) Package Insert
Ropinirole hydrochloride (RequipT) Package Insert
Temazepam (Restoril®) Package Insert
Tizanidine (Zanaflex®) Package Insert
Triazolam (Halcion®) Package Insert
Valproate (Depakene®) Package Insert

Click 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)

amantadine
baclofen
botulinum toxin
tizanidine OR Zanaflex
dantrolene OR dantrium
diazepam OR Valium
dopamine agonists
apomorphine
bromocriptine
cabergoline
pergolide
pramipexole
ropinirole
levodopa/carbidopa
COMT inhibitors
entacapone
tolcapone

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AMANTADINE
1. 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 study.

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.
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ARTANE
My 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.
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CLOZAPINE - 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.

Unfortunately, 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.

In addition, clozapine-treated patients showed significant improvement in
reduction of hallucinations and overall behavior while olanzapine had no effect.

(Medscape users see
http://neurology.medscape.com/medscape/features/JournalScan/Neurology/2000/js-neu0210.html#J2.3
for full article
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DIAZAPAN/VALIUM

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
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FLUOXETINE

Fluoxetine 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.
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Single Fluoxetine Dose Improves Motor Skills Impaired by Stroke
NEW 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.

In 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 motor cortex.
Ann Neurol 2001;50:718-729.
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LAMOTRIGINE/LAMICTAL (see other page)
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NABILONE
Nabilone increases choreatic movements in Huntington's disease
Mov Disord 1999 Nov;14(6):1038-40 (ISSN: 0885-3185)
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OLZANZAPINE-ZYPREXA

Family 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.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 )

The mechanism by which olanzapine may have beneficial effects is unclear.
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

Zyprexa/Olanzapine
http://www.mentalhealth.com/drug/p30-o02.html
Patients 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 50
to 60% Elderly or debilitated patients (late stage HD) should be monitored closely if on other drugs.

Tell your 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).

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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.html
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The 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 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.

This binding profile is similar to clozapine, another atypical antipsychotic drug, but substantially different to the conventional antipsychotic haloperidol.

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.

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

Full study available at JNNP OnLine
http://jnnp.bmjjournals.com/cgi/content/full/67/1/123?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&titleabstract=Huntington%27s+Diseas
e&fulltext=Huntington%27s+Disease&searchid=QID_NOT_SET&stored_search=&FIRSTINDEX=50&journalcode=jnnp

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RAGLAN/METOCLOPRAMIDE

All family experiences: do NOT take in HD can have severe consequences.

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TETRABENAZINE

Subject: Tetrabenazine for Huntington's Disease (AAN 2001)
Date: 5/8/01 http://www.wemove.org/emove/article.asp?ID=319

E-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 affected.

Adverse effects included akathisia, constipation, drooling, and insomnia, most of which resolved with dose adjustment.
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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.