Medication Summary
Although no therapy is currently available to delay the onset of symptoms or prevent the progression of the disease, symptomatic treatment of patients with Huntington disease (HD) may improve the quality of life and prevent complications. As is the case with other neurological diseases, HD makes individuals more vulnerable to side effects from medications, particularly cognitive adverse effects. Avoid polypharmacy if possible. Symptomatic treatment for HD can be divided into drugs to treat the movement disorder and drugs to treat psychiatric or behavioral problems.
Experimental therapies for HD currently are being tested in animal models and human trials. Awareness of ongoing research to find an effective cure for HD must be a part of the care plan of an individual patient and the patient's family.
Therapeutic options include dopamine-depleting agents (eg, reserpine, tetrabenazine) and dopamine-receptor antagonists (eg, neuroleptics). Long-term use of these drugs may carry a high risk of adverse effects. Choreic movements in patients with HD should be treated pharmacologically only if they become disabling to the patient. Neuroleptics may worsen other features of the disease, such as bradykinesia and rigidity, leading to further functional decline.
Results of some studies have suggested that valproic acid and clonazepam may be effective in the treatment of chorea, while results of other studies have been less conclusive. In the authors' experience, using valproic acid and clonazepam first may be worthwhile because of their safer adverse-effect profiles.
Tetrabenazine is a dopamine-depleting agent was approved by the FDA in August 2008. It may be more effective than reserpine in the treatment of chorea and less likely to cause hypotension. The dose is titrated slowly and may be increased over several weeks to a maximum 75-100 mg/d in divided doses.
Monoamine Inhibitors
Class Summary
Antichorea effect of central monamine-depleting agents is believed to be related to its effect on reversible depletion of monoamines (eg, dopamine, serotonin, norepinephrine) from nerve terminals.
Tetrabenazine (Xenazine)
Depletes neurotransmitter stores of dopamine, serotonin, and noradrenaline within nerve cells in the brain, thereby altering transmission of electric signals from the brain that control movement by reversibly inhibiting vesicular monoamine transporter 2 (VMAT2).
Efficacy and safety established in a randomized, double-blind, placebo-controlled, multicenter study. Patients treated with tetrabenazine had significant improvement in chorea compared with those treated with placebo. Additional studies support this effect. Indicated for chorea associated with Huntington disease.
Deutetrabenazine (Austedo)
Orally administered VMAT-2 inhibitor. It is indicated for chorea associated Huntington disease.
Reserpine
Dopamine-depleting agent. Used in past to treat hypertension.
Anticonvulsant
Class Summary
These agents are used to manage muscle spasms in chorea.
Valproic acid (Depakote, Depakene, Depacon)
Carboxylic acid commonly used as antiepileptic drug, mood stabilizer in mania, and prophylactic agent for migraine. When combined with sodium valproate in 1:1 molar relationship, called divalproex sodium. Mechanism by which valproate exerts its antiepileptic effects has not been established; its activity may be related to increased brain levels of GABA. No large clinical trials exist to support its use for hyperkinetic movement disorders, but it may be effective, as suggested by a few small studies in patients with chorea of different etiologies.
Daily maximum dose of 2000 mg in divided doses (bid or tid) is enough to determine whether drug is going to be effective for individual patient.
Clonazepam (Klonopin)
Belongs to benzodiazepine class of drugs. Enhances activity of GABA, major inhibitory neurotransmitter in CNS. Used commonly as antiepileptic drug. May be useful in treatment of chorea, but no large clinical trials exist to support its use. Does not induce parkinsonism or carry risk of tardive syndromes, as neuroleptics do; therefore, an adequate trial with this medication is reasonable before using dopamine antagonists.
Maximum daily dose of 2-4 mg divided bid/tid usually is enough to determine effectiveness for individual patient.
Antipsychotic agents
Class Summary
These agents may improve choreic movements in patients.
Risperidone (Risperdal)
Antipsychotic agent that belongs to new chemical class, benzisoxazole derivatives.
Antagonist of type 2 dopamine and serotonin receptors.
Less likely than typical neuroleptics to cause parkinsonism.
Haloperidol (Haldol)
First of butyrophenone class of major tranquilizers. Typical neuroleptics, such as haloperidol, are potent dopamine-receptor antagonists and should be used only as last resort to treat chorea.
Antidepressants
Class Summary
Depression is relatively common in patients with HD and should be treated pharmacologically as soon as diagnosis of depression is made. Depression in patients with HD can be treated with the same agents used for treatment of depression of any other cause. SSRIs may be used as first-line therapy because of their low adverse-effect profile, convenient dosing, and safety in the event of overdose. Other antidepressants can be used, including bupropion, venlafaxine, nefazodone, and the tricyclic antidepressants. Electroconvulsive therapy can be effective if an immediate intervention is required and in patients who do not respond to several good trials of medication.
Paroxetine (Paxil)
SSRI that can be used once daily. Most patients should take it in morning because can be stimulating and may cause insomnia. If sedation occurs, drug should be taken at bedtime. A few patients develop sexual problems, such as decreased libido, anorgasmia, or ejaculatory delay.
