Three classes of medication are commonly used to suppress chorea in Huntington's disease:
neuroleptics, such as haloperidol and fluphenazine; benzodiazepines, such as clonazepam and diazepam; and dopamine depleting
agents, such as reserpine and tetrabenazine. Each class has its advantages and disadvantages.
The suppression of movement, regarded as a side effect when neuroleptics are used to treat
psychosis, is the desired effect when they are used to treat chorea. Therefore the most popular neuroleptic agents are the
high potency drugs, which can also induce the most parkinsonism.
Haloperidol and fluphenazine are most commonly prescribed. They should be started at a low
dose, 0.5 to lmg once or twice a day, and gradually increased to efficacy. Doses higher than 6-8mg per day have not generally
been found helpful in treating chorea.
Risperidone is a newer neuroleptic which does not cause as much parkinsonism as the other
high potency agents, but is still useful in suppressing chorea and may relieve agitation as well. It may be also be started
at 0.5-lmg once or twice a day, with some patients tolerating doses as high as 6-8mg daily.
In some cases, patients who experience unacceptable rigidity, akathisia, or dystonia with
high potency agents may benefit from a lower potency neuroleptic such as thiothixene or thioridazine. This may be preferable
to adding an anticho-linergic agent to the original drug to counteract the side effects.
Lower potency agents tend to be more sedating, however, and are more inherently anticholinergic,
producing more tachy-cardia, postural hypotension, constipation, and delirium. Thiothixene can be started at l-2mg once or
twice a day and increased to 10-20mg/day. Thioridazine, which is even lower potency, can be started at l0mg once or twice
a day and increased to about l00mg/day.
Patients starting neuroleptics should be warned about two unlikely, but potentially serious
The first is tardive dyskinesia, a syndrome of involuntary movements often
first noted in the face and mouth, that develops in some patients taking neuroleptics.
Tardive dyskinesia is of concern because the symptoms are usually permanent, and will likely
be hard to recognize in someone with HD.
The other serious problem is neuroleptic malignant syndrome, a rare, but
life threatening reaction characterized by acute onset of delirium, rigidity, and fever, often accompanied by leukocytocis,
and elevated CPK. Families should know about this so that the patient can be given prompt medical attention if it develops.
Benzodiazepines, such as clonazepam and diazepam can also be useful in the treatment of
chorea. Some clinicians prefer them to neuroleptics because they do not induce parkinsonism or tardive dyskinesia. Sedation and the increased risk of delirium are the main deleterious side effects, along with tolerance,
withdrawal symptoms, and the potential for abuse.
Long acting varieties such as clonazepam and diazepam are favored because they require less
frequent dosing, provide more even coverage of symptoms throughout the day, and are less likely to precipitate withdrawal
symptoms if a dose is missed. Clonazepam may be started at 0.5mg per day, and may be raised as high as 4mg per day, in divided
doses. Diazepam may be dosed from about 1.25mg to 20mg per day, also in divided doses.
Some clinicians favor dopamine depleting agents as a treatment for chorea. While these drugs
do share some of the "neuro-leptic" side effects, they may be milder at low doses, and they have not been shown to cause tardive
dyskinesia. The class includes reserpine and tetrabenazine, which is not sold in the
United States, but is used widely in Europe.
Reserpine was used in the past as an antihypertensive, and may cause hypotension. This can
be minimized by giving the drug at bedtime. Parkinsonism, restlessness, dizziness, and sedation are other common side effects.
The increased rate of depression in patients taking these agents is also of concern. Reserpine may be started at 0.lmg per
day and increased weekly to a dose as great as 3mg per day.
Tetrabenazine is similar in action to reserpine, but is felt by some clinicians to be more
effective and is less likely to cause hypotension. It can be started at 12.5mg bid or tid and increased over several weeks
to a maximum of 75 or l00mg per day in divided doses. Tetrabenazine may be obtained from John Bell & Croyden in the UK
by calling 011-44-171-935-5555 or faxing a prescrip-tion to 011-44-171-935-9605. The drug is costly and probably will not
be covered by insurance.