What is the best medication for treating Huntington's disease (HD) chorea?

Best Medication for Treating Huntington's Chorea

Deutetrabenazine (Austedo) is the best medication for treating chorea associated with Huntington's disease due to its better tolerability profile compared to tetrabenazine while maintaining similar efficacy. 1

First-Line Medication Options

VMAT2 Inhibitors

These medications are the most effective for treating Huntington's chorea:

1. Deutetrabenazine (Austedo)

   • FDA-approved for Huntington's chorea 2
   • Better tolerability profile than tetrabenazine 1
   • Requires less frequent dosing
   • Lower peak-dose side effects 3

2. Tetrabenazine

   • FDA-approved specifically for Huntington's chorea 4
   • Efficacy: 75% of patients show marked or very good responses with long-term treatment 5
   • Dosing: Start at 12.5 mg/day, gradually titrate to effective dose (typically 25-75 mg/day) 1, 4
   • Maximum recommended daily dose: 100 mg (for extensive metabolizers) 4
   • Limitations: Higher risk of depression, suicidality, and somnolence 4, 6

3. Valbenazine (Ingrezza)

   • Improved side effect profile 1
   • Once-daily dosing

Treatment Algorithm

1. Initial Assessment

   • Determine severity of chorea and impact on daily functioning
   • Screen for depression, suicidality, and psychiatric symptoms
   • Consider CYP2D6 metabolizer status before prescribing tetrabenazine at doses >50 mg/day 4

2. First-Line Treatment

   • Start with deutetrabenazine (Austedo) due to better tolerability profile
   • Begin with low dose and titrate slowly to minimize side effects
   • Monitor for effectiveness in reducing chorea and impact on function

3. Alternative Options (if first-line ineffective or not tolerated)

   • Switch to tetrabenazine or valbenazine
   • Consider antipsychotics if psychiatric symptoms are also present

4. For Patients with Prominent Psychiatric Symptoms

   • Consider antipsychotics with antichorea effects:
     • Haloperidol
     • Sulpiride
     • Quetiapine 7, 1

Monitoring and Follow-up

• Regular assessment of chorea control
• Monitor for depression and suicidality (especially with tetrabenazine)
• Assess for side effects: somnolence, insomnia, parkinsonism, akathisia
• Evaluate swallowing function and fall risk

Important Considerations

• Real-world data shows many patients receive suboptimal dosing of tetrabenazine (average 45.5 mg/day vs. potential effective doses up to 100 mg/day) 8
• Discontinuation rates are high with tetrabenazine (41.8% of patients), with median time to discontinuation of 293.5 days 8
• Common adverse events with tetrabenazine include somnolence (39%), insomnia (33%), depression (31%), and dysphagia (19%) 5
• Chorea severity and non-persistence to treatment are associated with increased emergency room visits and hospitalizations 9

Emerging Therapies

Research into disease-modifying treatments is ongoing, including:

• Antisense oligonucleotide (ASO) therapy targeting mutant huntingtin protein 7
• Gene therapy approaches targeting CAG repeat expansion 1
• Small molecule splice modulators like Branaplam (LMI070) 7

These emerging therapies may eventually provide more comprehensive treatment options, but currently, deutetrabenazine represents the best balance of efficacy and tolerability for managing Huntington's chorea.