What medications are used to treat tardive dyskinesia?

Medications for Tardive Dyskinesia

Patients with moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy should be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) such as deutetrabenazine or valbenazine. 1, 2

First-Line Treatment Options

VMAT2 Inhibitors

VMAT2 inhibitors are the treatment of choice for tardive dyskinesia (TD) based on the strongest clinical evidence:

1. Valbenazine (Ingrezza)

   • FDA-approved specifically for TD
   • Dosing: Once-daily administration
   • Starting dose: 40 mg daily, target dose: 80 mg daily
   • Advantages: Convenient once-daily dosing, rapid onset of effect within 2 weeks 3, 4

2. Deutetrabenazine (Austedo)

   • FDA-approved specifically for TD
   • Dosing: Twice-daily administration with food
   • Effective doses: 24-36 mg/day 5, 6
   • Should be titrated gradually to minimize side effects

Both medications have demonstrated significant reduction in TD symptoms as measured by the Abnormal Involuntary Movement Scale (AIMS), with response rates (defined as 50% symptom reduction) ranging from 33% to 50% 6.

Management Algorithm for Tardive Dyskinesia

1. Prevention is primary

   • Use antipsychotics only when clinically indicated
   • Use minimum effective doses
   • Regular monitoring using AIMS every 3-6 months 2
   • Record baseline abnormal movements before starting antipsychotics

2. When TD is diagnosed:

   • Step 1: If clinically feasible, discontinue or reduce the causative antipsychotic medication 2, 7
   • Step 2: If antipsychotic discontinuation is not possible, consider switching to an atypical antipsychotic with lower D2 receptor affinity (e.g., clozapine, quetiapine) 2, 7
   • Step 3: Initiate VMAT2 inhibitor therapy (valbenazine or deutetrabenazine) 1, 2

Important Considerations and Precautions

Medications to Avoid

• Anticholinergics (benztropine, trihexyphenidyl) should be avoided as they may worsen TD symptoms 2
• These medications have a limited and potentially problematic role in TD management and may aggravate symptoms, especially in cases without coexisting drug-induced parkinsonism

Monitoring

• Regular assessment using the AIMS is recommended to track treatment response
• Monitor for potential side effects of VMAT2 inhibitors:
  • Somnolence and fatigue (most common)
  • Akathisia
  • Parkinsonism symptoms 3

Special Populations

• Elderly patients are at higher risk for developing TD (up to 50% after 2 years of continuous typical antipsychotic use) 2
• Patients with hepatic impairment may have contraindications to certain medications (e.g., deutetrabenazine) 8
• Patients with Huntington's disease require careful monitoring for depression and suicidal ideation when using VMAT2 inhibitors 3

Alternative Treatments with Limited Evidence

These options may be considered when VMAT2 inhibitors are not available or not tolerated:

• Amantadine - limited evidence of efficacy 9
• Clonazepam - limited efficacy in treating TD 2, 9
• Ginkgo biloba - some evidence of benefit 9
• Beta-blockers - may provide some relief but evidence is not strong 2

VMAT2 inhibitors represent a significant advancement in TD treatment as they specifically target the underlying mechanism of the disorder without the risk of causing or worsening TD, unlike dopamine receptor blocking agents that have historically been used to manage hyperkinetic movement disorders 9.