What is the recommended dose and onset of action of Ingrezza (valbenazine) for treating tardive dyskinesia?

Ingrezza (Valbenazine) for Tardive Dyskinesia: Dosing and Onset of Action

Valbenazine (Ingrezza) is the first FDA-approved medication for tardive dyskinesia with once-daily dosing and demonstrates rapid efficacy within 2 weeks of treatment initiation. 1

Recommended Dosing

• Initial dose: 40 mg once daily
• Maintenance dose: 80 mg once daily (after 4 weeks)
• Dose adjustment: Dose can be reduced to 40 mg daily if 80 mg is not tolerated 2

Onset of Action and Efficacy

• Rapid onset: Effects typically begin within 2 weeks of starting treatment 1
• Maximum benefit: Significant improvements observed at 6 weeks in clinical trials 3
• Long-term efficacy: Benefits are maintained with continued treatment for periods exceeding 1 year 2, 4

Clinical Evidence

The KINECT 3 trial, a phase 3 randomized controlled study, demonstrated significant improvement in tardive dyskinesia symptoms with valbenazine:

• 80 mg/day group showed mean AIMS score reduction of -3.2 compared to -0.1 for placebo
• 40 mg/day group showed mean AIMS score reduction of -1.9 3

Long-term extension studies showed:

• Sustained improvement in tardive dyskinesia symptoms
• High patient satisfaction (>98% of participants rated as "very satisfied" or "somewhat satisfied") 2
• Return of symptoms toward baseline after discontinuation, indicating need for continued treatment 4

Safety Profile

• Generally well-tolerated in clinical trials
• Common adverse events: No single adverse event occurred in ≥5% of participants in long-term studies 2
• Psychiatric stability: Treatment does not appear to worsen underlying psychiatric conditions 3
• No significant risk for inducing or worsening akathisia or parkinsonism 4

Important Considerations

• Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor
• Regular monitoring using the Abnormal Involuntary Movement Scale (AIMS) is recommended every 3-6 months 5
• If discontinuing treatment, be aware that TD symptoms typically return after washout period 4

Treatment Algorithm for Tardive Dyskinesia

1. First-line approach: Consider discontinuing the causative antipsychotic if clinically feasible
2. Second-line approach: If discontinuation not possible, switch to an atypical antipsychotic with lower D2 affinity
3. VMAT2 inhibitor therapy: Initiate valbenazine at 40 mg daily, titrating to 80 mg daily after 4 weeks based on response and tolerability 5

Common Pitfalls to Avoid

• Misdiagnosis: TD may be confused with akathisia or withdrawal dyskinesia 5
• Inappropriate medication use: Avoid using anticholinergics like benztropine (Cogentin) or trihexyphenidyl (Artane) for TD management as they may worsen symptoms 6, 5
• Inadequate monitoring: Failure to establish baseline abnormal movements before starting antipsychotic therapy 5
• Premature discontinuation: Be aware that benefits diminish after stopping treatment, with symptoms returning toward baseline after 4 weeks of washout 4