What is the treatment approach for chorea?

Treatment Approach for Chorea

Dopamine antagonists and VMAT2 inhibitors are the first-line pharmacological treatments for chorea, with selection based on comorbid conditions and side effect profiles. 1, 2

Evaluation and Diagnosis

• Brain MRI without contrast is the optimal imaging modality for patients with chorea to identify structural causes and assess for neurodegenerative patterns, though it may be normal early in disease course 1
• Genetic testing is recommended for suspected Huntington's disease (HD), the most common cause of adult-onset chorea, to detect CAG repeat expansions in the huntingtin gene 1
• Evaluation should identify potential secondary causes of chorea including cerebrovascular disease, infectious, autoimmune, metabolic, and drug-induced syndromes 1

Pharmacological Management

First-Line Options

• VMAT2 inhibitors:

  • Tetrabenazine: Effective for chorea reduction with dosing starting low and titrated weekly based on response and tolerability 3
  • Deutetrabenazine (AUSTEDO): FDA-approved for HD chorea with potentially improved side effect profile compared to tetrabenazine 2, 4
  • Starting dose for deutetrabenazine is 6 mg twice daily (12 mg/day) with food, titrating weekly by 6 mg/day up to maximum 48 mg/day based on response and tolerability 2

• Antipsychotic drugs (APDs):

  • Particularly tiapride (in European countries), olanzapine, and risperidone are preferred first-choice alternatives 5
  • APDs are preferred when comorbid psychotic or aggressive behaviors are present 5
  • Should be used as first-line when active depression prevents the use of VMAT2 inhibitors 5

Treatment Selection Considerations

• Geographic practice variations exist, with European experts favoring antipsychotics while North American experts are split between antipsychotics and tetrabenazine as first-line therapy 5
• For HD-related chorea with comorbid depression, avoid tetrabenazine due to its potential to worsen depressive symptoms 2, 5
• For chorea associated with antiphospholipid antibodies/syndrome, consider antiplatelet and/or anticoagulation therapy in addition to symptomatic treatment 1

Combination Therapy

• Consider combination of an antipsychotic and VMAT2 inhibitor when:
  • Severe chorea is inadequately controlled by either drug alone 5
  • Treatment requires both drugs for control of chorea and a concurrent comorbid symptom 5
• Benzodiazepines are not effective as monotherapy but may be useful as adjunctive therapy, particularly when chorea is exacerbated by anxiety 5

Immunomodulatory Therapy

• For chorea related to systemic lupus erythematosus or other autoimmune conditions, glucocorticoids alone or in combination with immunosuppressive therapy (azathioprine, cyclophosphamide) may be used 1
• Pulse intravenous methylprednisolone with intravenous cyclophosphamide has shown effectiveness in refractory cases with generalized autoimmune activity 1

Special Considerations

• Huntington's Disease Warning: VMAT2 inhibitors carry a boxed warning for depression and suicidality in HD patients; monitor patients closely for emergence or worsening of depression or suicidal thoughts 2
• Contraindications for VMAT2 inhibitors: Suicidal ideation, untreated/inadequately treated depression, hepatic impairment, concomitant use of MAOIs, reserpine, tetrabenazine, or valbenazine 2
• Dosing in poor CYP2D6 metabolizers: Maximum recommended dosage of deutetrabenazine is 36 mg per day 2
• QT prolongation: Avoid VMAT2 inhibitors in patients with congenital long QT syndrome or arrhythmias associated with prolonged QT interval 2

Treatment Monitoring

• Monitor for common side effects of VMAT2 inhibitors including somnolence, diarrhea, dry mouth, and fatigue 2
• Watch for potential development of akathisia, agitation, restlessness, and parkinsonism; reduce dose or discontinue if these occur 2
• Regularly assess treatment efficacy using standardized rating scales such as the Unified Huntington's Disease Rating Scale (UHDRS) for HD-related chorea 3
• Despite available treatments, only about 36% of patients with HD-related chorea receive medications specifically indicated for chorea management 6

Non-Pharmacological Approaches

• Physical therapy may help maintain mobility and prevent falls in patients with chorea 7
• Speech therapy for patients with orofacial chorea affecting speech and swallowing 1
• Occupational therapy to assist with activities of daily living impacted by choreiform movements 1