What are the best treatments for Tardive Dyskinesia (TD)?

Best Treatments for Tardive Dyskinesia (TD)

VMAT2 inhibitors (valbenazine or deutetrabenazine) are the first-line treatments for tardive dyskinesia while maintaining appropriate therapy for the underlying psychiatric condition. 1

Understanding Tardive Dyskinesia

Tardive dyskinesia (TD) is a movement disorder characterized by involuntary, repetitive movements primarily affecting the orofacial region (tongue protrusion, lip smacking) and extremities. It develops after prolonged exposure to dopamine receptor blocking agents, particularly antipsychotics, and can persist even after discontinuation of the causative medication.

Risk Factors

• Duration of antipsychotic treatment (up to 50% risk after 2 years of continuous use of typical antipsychotics in elderly patients)
• Higher cumulative dose of antipsychotics
• Older age
• Female gender
• Higher baseline AIMS scores
• Intellectual impairment 1

Treatment Algorithm

First-Line Treatments:

1. VMAT2 Inhibitors:

   • Valbenazine (Ingrezza): FDA-approved, 40 mg starting dose with target dose of 80 mg once daily. Response rates of 33-50% 1, 2
   • Deutetrabenazine (Austedo): FDA-approved, effective doses of 24-36 mg/day, requires twice-daily administration with food 1, 3

   Important note: For CYP2D6 poor metabolizers, dosage reduction of valbenazine is recommended due to approximately 2-fold higher exposure to the active metabolite 2

Second-Line Approaches (if VMAT2 inhibitors are not tolerated or available):

1. Medication Adjustment:

   • If clinically feasible, withdraw the causative antipsychotic medication 4, 5
   • Switch from first-generation to second-generation antipsychotic with lower D2 affinity (clozapine or quetiapine) 1, 4, 5
   • Reduce dose of conventional antipsychotics (contrary to some beliefs, dose reduction tends to improve rather than exacerbate TD) 6

2. Alternative Agents:

   • Amantadine
   • Benzodiazepines (clonazepam)
   • Ginkgo biloba
   • Beta-blockers 1

Monitoring and Assessment

• Use standardized assessment tools like the Abnormal Involuntary Movement Scale (AIMS) to monitor TD severity
• Perform assessments every 3-6 months 1
• The AIMS evaluates 7 body regions on a 0-4 scale, with total scores ranging from 0-28 (lower scores indicate improvement) 3, 2

Important Considerations and Pitfalls

Medication Management Pitfalls:

• Avoid anticholinergics: Medications like benztropine and trihexyphenidyl may worsen TD symptoms 1
• Tapering considerations: When discontinuing anticholinergics, taper slowly over 1-2 weeks to minimize withdrawal-emergent dyskinesia 1
• Clozapine caution: While clozapine may reduce TD severity, it appears to provide temporary suppression rather than permanent resolution 7

Special Populations:

• Elderly patients: Higher risk for TD development (up to 50% after 2 years of continuous typical antipsychotic use) 1
• Hepatic impairment: May have contraindications to certain medications like deutetrabenazine 1
• Huntington's disease patients: Require careful monitoring for depression and suicidal ideation when using VMAT2 inhibitors 1

Prevention Strategies

• Limit exposure to dopamine receptor blocking agents when possible
• Use minimum effective doses of antipsychotics
• Conduct regular monitoring with AIMS every 3-6 months
• Document baseline abnormal movements before starting antipsychotics 1

TD can significantly impact quality of life, with affected patients experiencing poorer prognoses, worse health-related quality of life, greater social withdrawal, and higher mortality than patients without TD 5. Early intervention with VMAT2 inhibitors offers the best chance for symptom improvement while allowing continued treatment of the underlying psychiatric condition.