What is the management plan for chorea (involuntary movements)?

From the Guidelines

The management of chorea involves addressing both the underlying cause and symptomatic treatment, with dopamine-blocking agents being first-line therapy, as seen in the 2020 study on movement disorders and neurodegenerative diseases 1. The primary goal is to identify and treat the primary etiology, which may include Huntington's disease, Sydenham's chorea, drug-induced chorea, or metabolic disorders.

• For symptomatic treatment, haloperidol starting at 0.5-1 mg daily and titrating up as needed (maximum 5-10 mg daily) is effective, as it modulates dopaminergic pathways in the basal ganglia, which are typically overactive in chorea.
• Alternatively, atypical antipsychotics like risperidone (0.5-3 mg daily) or olanzapine (2.5-10 mg daily) may have fewer extrapyramidal side effects, making them a viable option for patients who are susceptible to these side effects.
• For Huntington's disease specifically, tetrabenazine (12.5-25 mg three times daily) or deutetrabenazine (6-48 mg daily in divided doses) can be used as they deplete presynaptic dopamine, providing relief from chorea symptoms.
• Valproic acid (250-500 mg twice daily) or clonazepam (0.5-2 mg twice daily) may help when chorea is refractory, as they have been shown to be effective in reducing symptoms in some patients. Regular monitoring for side effects is essential, particularly for extrapyramidal symptoms with antipsychotics and depression with tetrabenazine, as these can significantly impact the patient's quality of life. Supportive care including physical therapy, occupational therapy, and psychological support should complement pharmacological treatment to improve quality of life and functional status, as chorea can have a significant impact on a patient's daily life and overall well-being, as noted in the study on movement disorders and neurodegenerative diseases 1.

From the FDA Drug Label

Extensive and Intermediate CYP2D6 Metabolizers Genotyped patients who are identified as extensive (EMs) or intermediate metabolizers (IMs) of CYP2D6, who need doses of tetrabenazine tablets above 50 mg per day, should be titrated up slowly at weekly intervals by 12. 5 mg daily, to allow the identification of a tolerated dose that reduces chorea.

Doses above 50 mg per day should be given in a three times a day regimen. The maximum recommended daily dose is 100 mg and the maximum recommended single dose is 37. 5 mg.

The management plan for chorea (involuntary movements) involves titrating tetrabenazine tablets up slowly to a tolerated dose that reduces chorea. The dose should be individualized based on the patient's CYP2D6 metabolizer status. Key considerations include:

• Starting with a low dose and increasing gradually
• Using a three times a day regimen for doses above 50 mg per day
• Not exceeding the maximum recommended daily dose of 100 mg or single dose of 37.5 mg
• Monitoring for adverse reactions and adjusting the dose as needed 2

From the Research

Management Plan for Chorea

The management plan for chorea involves a combination of pharmacologic and nonpharmacologic treatment strategies 3. The first step in the approach to a patient with chorea is accurately defining the phenomenology, followed by an investigation into determining the etiology 3.

Pharmacologic Treatment Options

Several pharmacologic agents are available to reduce chorea in Huntington's disease, including:

• Tetrabenazine, a monoamine-depleting agent that acts by depletion of the monoamines serotonin, norepinephrine, and dopamine in the central nervous system (CNS) 4
• Deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects 5
• Tiapride, olanzapine, and risperidone, which are preferred first choice drugs to reduce chorea among HD experts 5
• Valbenazine, an inhibitor of presynaptic vesicular monoamine transporter type 2 (VMAT2) that causes striatal dopamine depletion 6
• Dopamine receptor blockers, such as antipsychotics, and other drugs, including anti-epileptics and anti-glutamatargics 6

Nonpharmacologic Treatment Options

Nonpharmacologic treatment options for chorea include:

• Deep brain stimulation, which is usually reserved for patients with disabling chorea despite optimal medical therapy 6
• Genetic testing, which has led to increased awareness of HD mimics, such as C9orf72 and IgLON5 3

Treatment Approach

The treatment approach for chorea involves:

• Starting with a low dose and increasing the dose with close monitoring of any adverse effects 5
• Recognizing causes that are reversible or have disease-modifying interventions 3
• Targeting transcription and translation of the mutant huntingtin protein as a potential disease-modifying strategy in Huntington disease (HD) 3
• Symptom-focused treatments, including a third vesicular monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and drugs to target irritability and cognitive impairment 3