What are the differences between Ingrezza (valbenazine) and Austedo (deutetrabenazine) for the treatment of tardive dyskinesia?

Differences Between Ingrezza and Austedo for Tardive Dyskinesia Treatment

Both Ingrezza (valbenazine) and Austedo (deutetrabenazine) are FDA-approved VMAT2 inhibitors with equivalent efficacy for treating moderate to severe tardive dyskinesia, and either agent is appropriate as first-line pharmacotherapy; selection should be based on dosing convenience, side effect profile, and cost considerations. 1

Efficacy Comparison

Both medications demonstrate similar clinical effectiveness in treating tardive dyskinesia:

• AIMS score reduction: Both agents reduce Abnormal Involuntary Movement Scale (AIMS) scores by 2-5 points from baseline 2
• Response rates: AIMS response rates (defined as ≥50% symptom reduction) range from 33% to 50% for both medications 2
• Evidence quality: Both have Level 1A evidence supporting their efficacy for TD, representing the only therapies with this level of evidence 1

The American Psychiatric Association recommends treating moderate to severe or disabling tardive dyskinesia with a VMAT2 inhibitor (valbenazine or deutetrabenazine) as first-line pharmacotherapy, without preferential recommendation for either agent. 1

Dosing Differences

Ingrezza (Valbenazine)

• Dosing range: 40-80 mg once daily 2
• Dosing simplicity: Once-daily administration provides convenience 2
• Titration: Less complex titration schedule

Austedo (Deutetrabenazine)

• Dosing range: 12-36 mg per day 2
• Dosing frequency: Typically requires twice-daily administration due to shorter half-life 3
• Titration: More gradual titration may be needed

Pharmacologic Mechanism Distinctions

While both inhibit VMAT2, they have distinct pharmacologic properties:

• Metabolite differences: The agents differ in their active metabolites and pharmacokinetic profiles 3
• Deuteration: Deutetrabenazine contains deuterium substitution, which affects its metabolic pathway 3
• Clinical significance: These pharmacologic differences may influence individual patient response, though head-to-head studies are lacking 2

Tolerability Profile

Both medications are well tolerated with similar adverse effect profiles:

• Most common side effects: Somnolence and akathisia are reported most frequently with both agents, though at low rates 2
• Overall tolerability: Both demonstrate good tolerability in randomized controlled trials 2
• Safety monitoring: Regular monitoring for movement disorders should continue regardless of which agent is selected 1

Selection Criteria

Agent selection should be guided by:

• Dosing convenience: Valbenazine's once-daily dosing may improve adherence compared to deutetrabenazine's twice-daily regimen 2
• Special populations: Manufacturer labeling provides specific recommendations for renal/hepatic impairment, drug interactions, and other special populations 2
• Cost considerations: Medication costs for long-term TD treatment are substantial, and cost may be a determining factor 1
• Individual patient factors: Consider patient-specific factors including comorbidities, concomitant medications, and ability to adhere to dosing schedules 2

Critical Caveats

• No head-to-head trials: Direct comparative studies are warranted to determine if either agent is preferable in terms of efficacy or tolerability 2
• Equivalent guideline status: Neither agent is preferentially recommended over the other in current clinical guidelines 1
• Not for acute EPS: These medications are specifically for tardive dyskinesia, not for acute dystonia or parkinsonism, which require different management 1
• Anticholinergics contraindicated: Do not use anticholinergic medications for TD, as they are ineffective and may worsen symptoms 1, 4

Monitoring Requirements

Regardless of which VMAT2 inhibitor is selected:

• AIMS assessment: Administer the Abnormal Involuntary Movement Scale every 3-6 months to assess TD severity and treatment response 1
• Ongoing evaluation: Regular follow-up is essential to assess ongoing need for treatment and medication adjustments 1