Is tetrabenazine helpful for managing chorea in Huntington's disease?

Tetrabenazine for Managing Chorea in Huntington's Disease

Tetrabenazine is an effective first-line treatment for chorea in Huntington's disease, significantly reducing chorea symptoms with a mean reduction of 5.0 units on the Unified Huntington's Disease Rating Scale compared to 1.5 units with placebo. 1

Efficacy and Mechanism of Action

• Tetrabenazine works by selectively depleting central monoamines through reversible binding to the type 2 vesicular monoamine transporter (VMAT2), effectively suppressing chorea symptoms 1
• Long-term studies demonstrate sustained efficacy for up to 80 weeks with a mean reduction in Total Maximal Chorea score of 4.6 units 2
• In clinical practice, approximately 75% of patients achieve either marked or very good responses at their optimal dosages 3
• Tetrabenazine is FDA-approved specifically for the treatment of chorea associated with Huntington's disease 4

Dosing Recommendations

• Initial dosing should start low at 12.5 mg once daily in the morning 4
• After one week, increase to 25 mg daily given as 12.5 mg twice daily 4
• Titrate slowly at weekly intervals by 12.5 mg daily to identify the optimal dose that reduces chorea and is tolerated 4
• For doses of 37.5-50 mg per day, administer in a three-times-daily regimen 4
• Maximum recommended single dose is 25 mg 4
• For doses above 50 mg daily, CYP2D6 genotyping is required to determine metabolizer status 4
  • Extensive/intermediate metabolizers: maximum 100 mg daily (maximum single dose 37.5 mg)
  • Poor metabolizers: maximum 50 mg daily (maximum single dose 25 mg)

Safety Considerations and Monitoring

• WARNING: Tetrabenazine carries a boxed warning for increased risk of depression and suicidal thoughts/behavior in Huntington's disease patients 4

• Close monitoring is essential for:

  • Depression or worsening of pre-existing depression 4
  • Suicidal thoughts or behaviors 4
  • Development of parkinsonism symptoms 2
  • Akathisia, which can be mistaken for worsening chorea 2, 3

• Most common adverse events (occurring in ≥5% of patients) include:

  • Somnolence/sedation (39%) 3
  • Insomnia (33%) 3
  • Depression (31%) 3
  • Accidental injury (26%) 3
  • Dysphagia (19%) 3

Important Clinical Considerations

• If adverse reactions occur (akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, sedation), stop titration and reduce the dose 4
• If adverse reactions persist despite dose reduction, consider discontinuing tetrabenazine or initiating specific treatment for the side effect (e.g., antidepressants) 4
• Tetrabenazine is contraindicated in patients who are actively suicidal or have untreated/inadequately treated depression 4
• Recent data from a large observational study suggests that with close clinical supervision, tetrabenazine treatment is not associated with increased risk of depressed mood, suicidal ideation, suicide attempts, or suicide compared to no treatment 5

Alternative Treatment Options

• Deutetrabenazine (Austedo) is a newer VMAT2 inhibitor that contains deuterium, which extends active metabolite half-lives and minimizes drug concentration fluctuations 6
• Indirect treatment comparisons suggest deutetrabenazine has a more favorable tolerability profile than tetrabenazine, with significantly lower risk of moderate to severe adverse events and neuropsychiatric adverse events 6
• Valbenazine (Ingrezza) is another option for treating chorea in Huntington's disease 7

Practical Management Tips

• Educate patients, caregivers, and families about the risk of depression and suicidality, instructing them to report concerning behaviors promptly 4
• Exercise particular caution in patients with a history of depression or prior suicide attempts/ideation, which are increased in frequency in Huntington's disease 4
• Consider CYP2D6 genotyping before exceeding 50 mg/day to optimize dosing and minimize adverse effects 4
• Tetrabenazine can be administered without regard to food 4