What are the next steps for treating tardive dyskinesia if a patient is refractory to Austedo (deutetrabenazine)?

Treatment Options for Tardive Dyskinesia Refractory to Austedo (Deutetrabenazine)

For patients with tardive dyskinesia who are refractory to Austedo (deutetrabenazine), switching to valbenazine, a different VMAT2 inhibitor, is the recommended next step in management. 1

First-Line Alternative Treatment

When a patient with tardive dyskinesia does not respond adequately to deutetrabenazine (Austedo), the following approach is recommended:

1. Switch to valbenazine (Ingrezza)
   • Valbenazine is an FDA-approved VMAT2 inhibitor specifically for tardive dyskinesia
   • Offers once-daily dosing with rapid onset of effect within 2 weeks 2
   • Pharmacologically distinct from deutetrabenazine as it is the purified parent product of one of the main tetrabenazine metabolites 3
   • No cross-resistance has been established between different VMAT2 inhibitors

Second-Line Options

If valbenazine is not effective or not tolerated, consider:

1. Atypical antipsychotic switch (if clinically appropriate)

   • Consider switching to an antipsychotic with lower D2 receptor affinity such as:
     • Clozapine
     • Quetiapine
   • These agents may reduce tardive dyskinesia symptoms while maintaining psychiatric stability 4

2. Adjunctive medications

   • Amantadine
   • Clonazepam (short-term use)
   • Ginkgo biloba
   • Zolpidem 3

Medication Management Considerations

• Dose optimization: Ensure adequate trial duration (at least 12 weeks) and appropriate dosing before declaring treatment failure 5

• Medication assessment: Review all current medications that may exacerbate TD symptoms and discontinue any non-essential dopamine receptor blocking agents if clinically feasible 1

• Regular monitoring: Continue to assess TD symptoms using standardized scales such as the Abnormal Involuntary Movement Scale (AIMS) every 3-6 months 1

Special Considerations

• Severity assessment: Treatment approach may differ based on whether TD is moderate to severe/disabling versus mild 1

• Psychiatric stability: Any medication changes must balance TD symptom management with maintaining psychiatric stability

• Potential pitfalls:

  • Avoid typical antipsychotics as they may worsen TD 1
  • Avoid anticholinergic medications for long-term TD management as they may mask symptoms temporarily but worsen them long-term 1
  • Be aware that TD may be irreversible in some cases despite appropriate treatment 4

Advanced Options for Refractory Cases

For cases that remain refractory to pharmacological interventions:

• Botulinum toxin injections: Consider for focal dyskinesias, particularly in the orofacial region 3

• Deep brain stimulation: May be considered in severe, disabling cases unresponsive to all other treatments 3

The management of tardive dyskinesia requires careful balancing of symptom control against the need for ongoing psychiatric treatment. While VMAT2 inhibitors represent the most evidence-based approach, switching between different agents in this class offers the best chance for symptom improvement when the initial agent fails.