What is the recommended treatment and dosage for tardive dyskinesia using Ingrezza (valbenazine)?

Ingrezza (Valbenazine) Treatment for Tardive Dyskinesia

For adults with tardive dyskinesia, Ingrezza (valbenazine) should be initiated at 40 mg once daily for one week, then increased to the recommended dosage of 80 mg once daily. 1

Dosing Protocol for Tardive Dyskinesia

• Initial dosage: 40 mg once daily
• After one week: Increase to 80 mg once daily (recommended maintenance dose)
• Alternative dosing: 40 mg or 60 mg once daily may be considered depending on response and tolerability 1, 2
• Administration: Can be taken with or without food 1
• Formulations:
  • INGREZZA capsules: 40 mg, 60 mg, and 80 mg
  • INGREZZA SPRINKLE capsules: Can be opened and sprinkled over soft food (do not use milk or drinking water) or swallowed whole with water (do not crush or chew) 1

Special Population Considerations

• Hepatic impairment: For patients with moderate or severe hepatic impairment, the recommended dosage is 40 mg once daily 1
• CYP2D6 poor metabolizers: The recommended dosage is 40 mg once daily 1
• Older adults: No dose adjustment required based on age; valbenazine is equally effective and well-tolerated in both older (≥55 years) and younger adults 3

Drug Interactions

Interacting Medication	Recommended Adjustment
MAOIs	Avoid concomitant use
Strong CYP3A4 inducers	Concomitant use not recommended
Strong CYP3A4 inhibitors	Reduce to 40 mg once daily
Strong CYP2D6 inhibitors	Reduce to 40 mg once daily

1

Efficacy

• The 80 mg dose shows the highest response rate, with approximately 40% of patients achieving ≥50% improvement in AIMS scores after 6 weeks of treatment 3
• The 60 mg dose provides intermediate efficacy between the 40 mg and 80 mg doses, with predicted mean AIMS change from baseline of -2.69 points 2
• Long-term treatment (48 weeks) shows increased response rates:
  • AIMS response (≥50% improvement): 70.7% in older adults, 58.7% in younger adults
  • CGI-TD response ("much improved" or "very much improved"): 82.8% in older adults, 72.3% in younger adults 3

Monitoring and Safety Considerations

• Common adverse effects: Somnolence (most common, ≥5% and twice the rate of placebo) 1
• QT prolongation: May cause increased QT interval; avoid use in patients with congenital long QT syndrome or arrhythmias associated with prolonged QT interval 1
• Somnolence/sedation: May impair ability to drive or operate hazardous machinery 1
• Parkinsonism: Monitor for parkinson-like symptoms; reduce dose or discontinue if clinically significant signs develop 1
• Neuroleptic Malignant Syndrome: Discontinue if this occurs 1
• Hypersensitivity: Including angioedema may occur; discontinue if this develops 1

Clinical Pearls

• Valbenazine is a selective inhibitor of vesicular monoamine transporter 2 (VMAT2), which reduces dopamine release in nerve terminals 4
• Unlike tetrabenazine, valbenazine requires only once-daily dosing due to its longer half-life 4
• Valbenazine does not antagonize postsynaptic monoamine receptors, potentially resulting in fewer motor and psychiatric side effects compared to tetrabenazine 4
• Regular monitoring for tardive dyskinesia using standardized scales (e.g., AIMS every 3-6 months) is recommended for all patients on antipsychotics 5
• Prevention remains critical: use antipsychotics only for specific indications, at minimum effective doses, and for shortest duration possible 5

Treatment Algorithm for Tardive Dyskinesia

1. First step: If clinically feasible, discontinue the causative antipsychotic
2. Second step: If discontinuation not possible, switch to an atypical antipsychotic with lower D2 affinity
3. Third step: If TD persists, initiate VMAT2 inhibitor therapy with valbenazine:
   • Start with 40 mg once daily for one week
   • Increase to 80 mg once daily (or consider 60 mg if concerns about tolerability)
   • Assess response after 6 weeks of treatment
   • Continue monitoring for adverse effects and efficacy

Valbenazine represents a significant advance in TD treatment as the first FDA-approved medication specifically for this condition, with demonstrated efficacy and tolerability in both short-term and long-term studies 6, 7.