How do you treat the symptoms of Huntington's chorea?

Symptomatic Treatment of Huntington's Chorea

For chorea in Huntington's disease, initiate tetrabenazine or deutetrabenazine as first-line therapy when chorea causes functional impairment, social isolation, gait instability, falls, or physical injury. 1, 2, 3

Indications for Pharmacological Treatment

Treatment should be initiated when chorea causes: 4

• Patient stigma or social isolation
• Physical injury or risk of falls
• Gait instability
• Work or daily activity interference
• Disturbed sleep

Do not treat chorea solely based on its presence—only treat when it impacts quality of life or safety. 3, 4

First-Line Pharmacological Options

VMAT2 Inhibitors (Preferred in North America/Australia)

Tetrabenazine is FDA-approved specifically for HD chorea: 2

• Start at 12.5 mg once daily in the morning
• Increase by 12.5 mg weekly as tolerated
• Divide doses when exceeding 37.5-50 mg/day
• Most patients respond to ≤50 mg/day total 5
• Maximum dose: 100 mg/day (requires genetic testing for doses >50 mg/day) 2

Critical contraindications for tetrabenazine: 2

• Active depression or suicidal ideation (absolute contraindication)
• Concurrent MAOI use
• Hepatic impairment
• Recent reserpine use (wait 20 days after stopping reserpine)

Deutetrabenazine (Austedo) offers similar efficacy with potentially fewer peak-dose side effects: 1, 3

• May be better tolerated than tetrabenazine
• Dosing similar but with improved pharmacokinetics

Antipsychotic Drugs (Preferred in Europe)

Tiapride (available in Europe): 6

• First-line choice among European HD experts
• Dose: 300-800 mg/day in divided doses
• Less depression risk compared to tetrabenazine
• Can be given at higher doses at night to improve sleep

Risperidone: 1, 6

• Dose: 0.5-4 mg/day
• Particularly useful when irritability or aggression coexists with chorea
• May also improve sleep disorders

Olanzapine: 1, 6

• Dose: 2.5-10 mg/day
• Beneficial for weight loss (common in HD)
• Dual benefit for chorea and weight maintenance

Quetiapine: 6

• Dose: 25-300 mg/day
• Useful when mood stabilization or antidepressant effect needed
• Lower risk of extrapyramidal side effects

Treatment Algorithm by Clinical Scenario

Chorea Alone (No Psychiatric Comorbidity)

• North America/Australia approach: Start tetrabenazine or deutetrabenazine 4
• European approach: Start tiapride 6, 4
• Both approaches are acceptable based on expert consensus 4

Chorea + Active Depression

• Use antipsychotic drugs only (risperidone, olanzapine, or quetiapine) 6, 4
• Tetrabenazine is contraindicated due to depression risk 2

Chorea + Psychosis or Aggression

• Use antipsychotic drugs (risperidone preferred) 6, 4
• Addresses both chorea and behavioral symptoms synergistically

Chorea + Weight Loss

• Use olanzapine 6
• Treats chorea while promoting weight gain

Chorea + Anxiety

• Add benzodiazepines as adjunctive therapy 4
• Benzodiazepines ineffective as monotherapy but useful when anxiety exacerbates chorea

Management of Inadequate Response

Severe Chorea Uncontrolled by Monotherapy

Combine drugs with different mechanisms: 6

• Postsynaptic dopamine blocker (tiapride or other antipsychotic) PLUS
• Presynaptic VMAT2 inhibitor (tetrabenazine or deutetrabenazine)
• This combination targets chorea through complementary pathways

Reasons for Stopping Dose Escalation

Common reasons include: 5

• Optimal chorea control achieved (55.5% of cases)
• Intolerance at higher doses (31.2% of cases)
• Maximum recommended dose reached despite suboptimal control (11.4% of cases)

Critical Monitoring and Side Effects

Monitor closely for: 2, 3

• Depression and suicidal ideation (especially with tetrabenazine)
• Sedation (common with all agents)
• Parkinsonism or worsening bradykinesia
• Akathisia
• Cognitive decline

Sedation management: 6

• Give highest daily dose at bedtime to improve sleep
• Avoid driving until sedation effects are known 2

Non-Pharmacological Approaches

Implement before or alongside medication: 1

• Establish predictable daily routines with consistent meal, activity, and sleep timing
• Create safe environment by removing hazards
• Reduce environmental stimuli that trigger agitation
• Speech therapy for orofacial chorea affecting swallowing 7
• Occupational therapy for activities of daily living 7

Common Pitfalls to Avoid

• Do not treat chorea in patients with active untreated depression with tetrabenazine 2
• Do not overlook non-pharmacological interventions before starting medication 1
• Do not use amantadine—experts describe benefit as small and transient 4
• Do not routinely use benzodiazepines as monotherapy—ineffective alone 4
• Do not continue dose escalation if patient develops intolerable side effects—most patients respond to lower doses 5
• Do not forget that emerging symptoms may be medication side effects rather than disease progression 6

Valbenazine Alternative

Valbenazine (Ingrezza) is also FDA-approved for HD chorea: 1

• Another VMAT2 inhibitor option
• Once-daily dosing may improve adherence