When should Austedo (deutetrabenazine) be used versus Ingrezza (valbenazine) for a patient with a movement disorder, such as Huntington's disease or tardive dyskinesia?

When to Use Austedo vs Ingrezza

Both Austedo (deutetrabenazine) and Ingrezza (valbenazine) are FDA-approved VMAT2 inhibitors that serve as first-line pharmacotherapy for moderate-to-severe tardive dyskinesia, with equivalent efficacy and safety profiles; however, Austedo has the additional FDA-approved indication for chorea associated with Huntington's disease, making it the clear choice when treating Huntington's disease-related movement disorders. 1, 2, 3

Primary Decision Algorithm

For Tardive Dyskinesia

• Either medication is appropriate as first-line treatment for moderate-to-severe or disabling persistent tardive dyskinesia, as both are VMAT2 inhibitors with Level 1A evidence supporting their use 1, 2
• The American Psychiatric Association recommends VMAT2 inhibitors (valbenazine or deutetrabenazine) as first-line pharmacotherapy without preference between the two agents 2
• Both medications demonstrate consistent efficacy regardless of underlying psychiatric illness or concurrent use of dopamine-receptor antagonists 4

For Huntington's Disease Chorea

• Austedo is the required choice as it is FDA-approved for chorea associated with Huntington's disease, whereas Ingrezza lacks this indication 5, 3
• Austedo demonstrated statistically significant improvement in Total Maximal Chorea Score (-2.5 units treatment effect, p<0.0001) in controlled trials 3
• 51% of patients treated with Austedo rated their symptoms as "Much Improved" or "Very Much Improved" compared to 20% on placebo 3

Pharmacokinetic Differences That May Guide Selection

Dosing Frequency

• Austedo requires twice-daily dosing (or once-daily with extended-release formulation), while Ingrezza is dosed once daily 6, 7
• Deutetrabenazine's active metabolites have a doubled elimination half-life compared to tetrabenazine, with lower peak-to-trough fluctuations (3- to 4-fold improvement) 7

Food Effects

• Austedo can be taken without regard to meals, as food has no effect on total exposure (AUC), though Cmax increases approximately 50% with food while remaining lower than tetrabenazine 7

Metabolic Considerations

• Austedo's active metabolites (α-HTBZ and β-HTBZ) are CYP2D6 substrates, with strong CYP2D6 inhibitors (e.g., paroxetine) increasing total exposure approximately 3-fold 3
• In the presence of strong CYP2D6 inhibitors, dose adjustments are necessary for Austedo 3

Practical Clinical Scenarios

When Austedo is Specifically Indicated

• Any patient with Huntington's disease-related chorea requires Austedo, as it is the only VMAT2 inhibitor with FDA approval for this indication 5, 3
• Patients already on tetrabenazine can be switched to Austedo the day following discontinuation 3

When Either Agent is Appropriate

• Tardive dyskinesia in patients on antipsychotics can be treated with either VMAT2 inhibitor with equivalent expected outcomes 1, 2
• Both medications show similar safety profiles to placebo in clinical trials 4

Critical Safety Considerations (Apply to Both Agents)

Absolute Contraindications

• Never use anticholinergics (benztropine, trihexyphenidyl) to treat tardive dyskinesia, as they may worsen the condition 1, 2, 8
• Concurrent use with tetrabenazine or the other VMAT2 inhibitor is contraindicated 3

Drug Interactions Requiring Caution

• Concomitant use with dopamine antagonists or antipsychotics increases risk of parkinsonism, neuroleptic malignant syndrome, and akathisia 3
• Alcohol or sedating drugs have additive effects on sedation and somnolence 3

Monitoring Requirements

• Use the Abnormal Involuntary Movement Scale (AIMS) to monitor treatment response at least every 3-6 months 2
• Document baseline abnormal movements before initiating therapy to avoid mislabeling pre-existing movements as treatment-emergent 1

Common Pitfalls to Avoid

• Do not confuse drug-induced parkinsonism with tardive dyskinesia: anticholinergics may benefit the former but worsen the latter 8
• Do not use these agents in pediatric populations: neither medication has established safety and efficacy in children for tardive dyskinesia or Huntington's disease, and Austedo failed to demonstrate efficacy in pediatric Tourette syndrome trials 3
• Do not overlook the option to discontinue the offending antipsychotic: if clinically feasible, gradual withdrawal remains the primary intervention when the underlying psychiatric condition allows 1, 2

Alternative Management if VMAT2 Inhibitors Are Not Suitable

• Switch to clozapine if continued antipsychotic therapy is necessary, as it has the lowest risk profile for movement disorders 2
• Consider atypical antipsychotics with lower D2 affinity if antipsychotic treatment must continue 1