Tetrabenazine (12.5–50 mg orally three times daily) depletes cerebral dopamine and reduces the severity of chorea. It has less troublesome adverse effects than reserpine, which has also been used for this purpose. Tetrabenazine is metabolized by cytochrome P450 (CYP2D6), and genotyping has therefore been recommended to determine metabolizer status (CYP2D6 expression) in patients needing doses exceeding 50 mg/d. For poor metabolizers, the maximum recommended dose is 50 mg daily (25 mg/dose); otherwise, a maximum dose of 100 mg daily can be used. Treatment with postsynaptic dopamine receptor blockers such as phenothiazines and butyrophenones may also be helpful. Haloperidol is started in a small dose, eg, 1 mg twice daily, and increased every 4 days depending on the response. If haloperidol is not helpful, treatment with increasing doses of fluphenazine in a similar dose, eg, 1 mg twice daily, sometimes helps. Several recent reports suggest that olanzapine may also be useful; the dose varies with the patient, but 10 mg daily is often sufficient, although doses as high as 30 mg daily are sometimes required. The pharmacokinetics and clinical properties of these drugs are considered in greater detail elsewhere in this book. Selective serotonin reuptake inhibitors may reduce depression, aggression, and agitation. However, strong CYP2D6 inhibitors should be used with caution, as it may be necessary to decrease the dose of tetrabenazine taken concurrently.
A novel agent, deutetrabenazine, which is a selective inhibitor of the vesicular monoamine 2 transporter (VMAT2) that modulates dopamine stores was approved by the FDA for the chorea of Huntington’s disease while this book was in press. The dose is built up weekly from  6 mg daily to a maximum of 24 mg twice daily with food (18 mg twice daily in poor CYP2DG metabolizers). Deutetrabenazine is contraindicated in patients on monoamine oxidase inhibitors, reserpine, or tetrabenazine, and in those who are severely depressed or suicidal.
Other important aspects of management include genetic counseling, speech therapy, physical and occupational therapy, dysphagia precautions, and provision of social services.
Other Forms of Chorea
Benign hereditary chorea is inherited (usually autosomal dominant; possibly also autosomal recessive) or arises spontaneously. Chorea develops in early childhood and does not progress during adult life; dementia does not occur. In patients with TITF-1 gene mutations, thyroid and pulmonary abnormalities may also be present (brain-thyroid-lung syndrome). Familial chorea may also occur as part of the chorea-acanthocytosis syndrome, together with orolingual tics, vocalizations, cognitive changes, seizures, peripheral neuropathy, and muscle atrophy; serum β-lipoproteins are normal. Mutations of the gene encoding chorein at 9q21 may be causal. Treatment of these hereditary disorders is symptomatic. Tetrabenazine (0.5 mg/kg/d for children and 37.5 mg/d for adults) may improve chorea in some instances.