What are the treatment options for tardive dyskinesia?

Treatment Options for Tardive Dyskinesia

The most effective treatments for tardive dyskinesia are the FDA-approved VMAT2 inhibitors valbenazine and deutetrabenazine, which should be considered first-line pharmacological interventions when discontinuation of the offending agent is not feasible. 1, 2, 3, 4

Prevention and Early Detection

• Prevention is critical as treatment options are limited once tardive dyskinesia (TD) develops 1
• Use atypical antipsychotics when possible, as they have lower TD risk compared to typical antipsychotics 5, 1
• Baseline assessment of abnormal movements should be recorded before starting antipsychotic therapy 1
• Regular monitoring using standardized measures like the Abnormal Involuntary Movement Scale (AIMS) should occur every 3-6 months 1

Management Algorithm

First-line Approaches:

1. Discontinuation of the offending agent

   • If clinically feasible, gradually withdraw the dopamine receptor-blocking medication 5, 1, 6
   • Abrupt discontinuation should be avoided as it may worsen TD symptoms 7

2. Switch to lower-risk antipsychotic

   • Consider switching to atypical antipsychotics with lower D2 affinity 1
   • Clozapine or quetiapine may be effective in reducing TD symptoms, though the effect may be temporary rather than permanent 6, 8

3. VMAT2 Inhibitors

   • Valbenazine and deutetrabenazine have demonstrated efficacy in multiple high-quality studies 2, 3, 4
   • Valbenazine showed statistically significant improvement in AIMS total score compared to placebo in clinical trials 2
   • Deutetrabenazine demonstrated significant improvement in AIMS total score in 12-week trials 3
   • Dosage considerations:
     • For valbenazine: Start at lower doses and titrate as needed, with dose reduction recommended in CYP2D6 poor metabolizers 2
     • For deutetrabenazine: Starting dose of 12 mg/day with weekly increases of 6 mg increments until optimal control is achieved 3

Special Considerations

• TD can affect any body part but typically involves the orofacial region 1
• Up to 50% of youth receiving neuroleptics may experience some form of tardive or withdrawal dyskinesia 5, 1
• The concern over TD should not outweigh potential benefits of antipsychotics for patients who genuinely need these medications 1
• Early detection is crucial as TD may persist even after medication discontinuation 1

Monitoring Treatment Response

• Regular follow-up is essential to assess ongoing need for treatment and medication adjustments 1
• Patient-rated and physician-rated global impression of change scales can help evaluate treatment effectiveness 2, 3
• In clinical trials of VMAT2 inhibitors, TD symptoms returned to baseline after discontinuation of treatment, suggesting ongoing treatment may be necessary for sustained benefit 2, 3

Pitfalls and Caveats

• Anti-emetics with dopamine receptor blocking properties (prochlorperazine, promethazine, metoclopramide) can also cause TD 7
• Patients may have multiple tardive syndromes simultaneously (dyskinesia, dystonia, akathisia) requiring different treatment approaches 7
• Discontinuation of clozapine may lead to reemergence of TD symptoms, suggesting it provides temporary suppression rather than permanent resolution 8
• There is no minimal safe duration of exposure to dopamine receptor blockers for the development of tardive syndromes 7