What is the best treatment for tardive dyskinesia due to stopped antipsychotic medication?

Treatment for Tardive Dyskinesia After Discontinuation of Antipsychotics

VMAT2 inhibitors (valbenazine or deutetrabenazine) are the first-line treatment for tardive dyskinesia that persists after antipsychotic discontinuation, with valbenazine offering the advantage of once-daily dosing and rapid onset of effect within 2 weeks. 1

First-Line Treatment Options

Valbenazine (Ingrezza)

• FDA-approved specifically for tardive dyskinesia
• Dosing:
  • Starting dose: 40 mg once daily
  • Target dose: 80 mg once daily
• Advantages:
  • Convenient once-daily dosing
  • Rapid onset of effect within 2 weeks
  • Significant reduction in TD symptoms with response rates of 33-50% 1
  • Strong efficacy demonstrated in clinical trials with effect size of 0.90 at 80 mg/day 2
  • Mean change in AIMS dyskinesia score of -3.2 for 80 mg/day group compared to -0.1 for placebo 3

Deutetrabenazine (Austedo)

• FDA-approved specifically for tardive dyskinesia
• Dosing:
  • Effective doses: 24-36 mg/day
  • Requires twice-daily administration with food
  • Gradual titration to minimize side effects 1
• Efficacy:
  • Demonstrated significant reduction in TD symptoms
  • Effectively controls involuntary movements according to rating scales 4
  • Well-tolerated with nasopharyngitis and insomnia being the most common side effects (>2%) compared to placebo 4

Special Considerations

Monitoring

• Regularly assess TD symptoms using the Abnormal Involuntary Movement Scale (AIMS)
• Monitor for potential side effects of VMAT2 inhibitors:
  • Depression and suicidal ideation
  • Somnolence
  • Balance issues 1

CYP2D6 Poor Metabolizers

• For valbenazine, dosage reduction is recommended in CYP2D6 poor metabolizers due to approximately 2-fold higher exposure of the active metabolite 5
• Consider genetic testing if available or if patient shows signs of increased side effects at standard doses

Contraindications and Precautions

• Avoid anticholinergics (benztropine, trihexyphenidyl) as they may worsen TD symptoms 1
• Patients with hepatic impairment may have contraindications to certain medications, such as deutetrabenazine 1
• For patients with Huntington's disease, careful monitoring for depression and suicidal ideation is required when using VMAT2 inhibitors 1

Second-Line Options

If VMAT2 inhibitors are not tolerated or available, consider:

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

Treatment Algorithm

1. Confirm diagnosis: Differentiate TD from other movement disorders like drug-induced parkinsonism, akathisia, and withdrawal dyskinesia
2. First-line treatment: Start VMAT2 inhibitor
   • Valbenazine 40 mg daily, titrate to 80 mg daily after one week if tolerated
   • OR Deutetrabenazine starting at lower doses and gradually titrating to 24-36 mg/day
3. Evaluate response: Assess improvement using AIMS at 2-4 weeks
4. Adjust treatment:
   • If good response: Continue treatment with regular monitoring
   • If partial response: Optimize dose of VMAT2 inhibitor
   • If poor response or intolerance: Consider switching to the alternative VMAT2 inhibitor or second-line options

Pitfalls to Avoid

• Do not restart antipsychotics if clinically feasible, as this may worsen TD
• Avoid anticholinergics which can exacerbate TD symptoms
• Don't confuse TD with withdrawal dyskinesia, which is temporary and resolves within weeks of medication discontinuation
• Don't assume TD will resolve spontaneously after antipsychotic discontinuation - many cases persist and require specific treatment

The evidence strongly supports VMAT2 inhibitors as the most effective treatment for tardive dyskinesia, with both valbenazine and deutetrabenazine demonstrating significant efficacy in reducing TD symptoms in clinical trials 3, 4. The choice between these two medications should be based on considerations such as dosing convenience, side effect profile, and patient-specific factors.