Which is more effective, Austedo (deutetrabenazine) or Ingrezza (valbenazine)?

Comparison of Austedo (Deutetrabenazine) and Ingrezza (Valbenazine) for Treatment of Movement Disorders

Austedo (deutetrabenazine) is the better choice for most patients with movement disorders due to its more extensive clinical evidence, better tolerability profile, and demonstrated efficacy in both chorea and tardive dyskinesia.

Mechanism of Action and Pharmacokinetics

Both medications are vesicular monoamine transporter 2 (VMAT2) inhibitors that work by regulating monoamine uptake into synaptic vesicles, thereby reducing abnormal involuntary movements:

• Austedo (deutetrabenazine): A deuterated form of tetrabenazine with improved pharmacokinetics

  • Deuterium substitution provides longer half-life and more stable blood levels
  • Requires twice-daily dosing
  • Maximum daily dose of 48 mg 1

• Ingrezza (valbenazine):

  • Once-daily dosing
  • Available in 40 mg and 80 mg doses

Efficacy Comparison

Clinical Evidence for Austedo:

• In the pivotal FIRST-HD trial, deutetrabenazine significantly improved chorea scores compared to placebo (mean difference -2.5 points, p<0.001) 2
• Treatment success measured by Patient Global Impression of Change occurred in 51% of deutetrabenazine patients vs. 20% with placebo (p=0.002) 2
• Clinical Global Impression of Change showed success in 42% of deutetrabenazine patients vs. 13% with placebo (p=0.002) 2
• Real-world data from University of Alabama showed a mean improvement in total maximal chorea scores of 4.4 points over an average treatment period of 476.4 days 3

Tolerability and Safety Profile:

• Austedo (deutetrabenazine):

  • In real-world studies, adverse events occurred in only 32.8% of patients
  • Most common side effects: sedation (15.5%), insomnia (6.9%), and diarrhea (3.4%) 3
  • Neuropsychiatric adverse events typically occurred in <7% of patients 4
  • Overall tolerability profile similar to placebo in clinical trials 4

• Comparative Safety:

  • While both medications are generally well-tolerated, indirect comparison studies suggest that deutetrabenazine may have a more favorable adverse effect profile 1
  • Somnolence is the most commonly reported adverse effect with both medications 5

Special Considerations

For Tardive Dyskinesia:

• Both medications have demonstrated efficacy in reducing Abnormal Involuntary Movement Scale (AIMS) scores by 2-5 points
• Response rates (defined as 50% reduction in symptoms) range from 33% to 50% for both medications 5
• The choice between them may be guided by:
  • Patient comorbidities
  • Dosing preference (once vs. twice daily)
  • Insurance coverage

For Huntington's Disease Chorea:

• Deutetrabenazine has robust evidence specifically for Huntington's disease chorea 4, 2, 3
• The ARC-HD trial demonstrated maintained efficacy with deutetrabenazine for up to 54 weeks 4

Practical Approach to Medication Selection

1. For patients with Huntington's disease chorea: Deutetrabenazine (Austedo) should be first-line due to its specific FDA approval and robust evidence base

2. For patients with tardive dyskinesia:

   • If once-daily dosing is critical for adherence: Consider valbenazine
   • If minimizing side effects is the priority: Deutetrabenazine may be preferable

3. For patients with comorbid psychiatric conditions:

   • Deutetrabenazine has shown a favorable neuropsychiatric side effect profile in clinical trials 4

Dosing Considerations

• Austedo (deutetrabenazine):

  • Starting dose: 6 mg/day (3 mg twice daily)
  • Titrate weekly by 6 mg/day to optimal dose
  • Maximum: 48 mg/day (24 mg twice daily)
  • Take with food

• Ingrezza (valbenazine):

  • Starting dose: 40 mg once daily
  • After one week, increase to 80 mg once daily
  • Can be taken with or without food

Conclusion

While both medications are effective VMAT2 inhibitors, the current evidence base favors deutetrabenazine (Austedo) due to its more extensive clinical data, favorable side effect profile, and demonstrated long-term efficacy. The choice between twice-daily dosing (Austedo) versus once-daily dosing (Ingrezza) may be a consideration for some patients, but should generally not outweigh the more established efficacy and safety profile of deutetrabenazine.