What are the management options for tardive dyskinesia?

Management of Tardive Dyskinesia

The first-line management of tardive dyskinesia (TD) is discontinuation of the causative antipsychotic medication if clinically feasible, followed by switching to an atypical antipsychotic with lower D2 affinity if discontinuation is not possible, and then considering VMAT2 inhibitors (valbenazine or deutetrabenazine) for persistent symptoms. 1, 2

Prevention and Risk Assessment

• Prevention is critical as TD can be persistent and challenging to treat
• Risk factors include:
  • Treatment with typical antipsychotics
  • Higher doses and longer duration of exposure
  • Older age (especially elderly females)
  • Female gender
  • Higher baseline AIMS scores
  • Intellectual impairment 1
• Regular monitoring using the Abnormal Involuntary Movement Scale (AIMS) every 3-6 months during antipsychotic therapy 1
• Record baseline measures of abnormal movements before starting antipsychotic therapy 1

Management Algorithm

Step 1: Discontinuation or Dose Reduction of Causative Agent

• If clinically feasible, discontinue the antipsychotic medication causing TD 1, 2
• Contrary to some beliefs, dose reduction of conventional antipsychotics typically improves rather than exacerbates TD 3
• Monitor closely as withdrawal dyskinesia may temporarily occur but typically resolves over time, unlike true TD 1

Step 2: Switch to Lower-Risk Antipsychotic (if discontinuation not possible)

• Switch from first-generation to second-generation antipsychotic with lower D2 receptor affinity
• Clozapine or quetiapine are preferred options due to their lower D2 affinity 2
• Atypical antipsychotics have shown effectiveness in treating TD and may reduce its prevalence and incidence 4

Step 3: VMAT2 Inhibitors

• For persistent TD symptoms, VMAT2 inhibitors are the treatment of choice 5
• FDA-approved options:
  1. Valbenazine: Demonstrated efficacy in reducing AIMS dyskinesia total score at 80mg daily dosage 6
  2. Deutetrabenazine: Shown to improve Total Maximal Chorea Score in patients with TD, with 51% of patients rating their symptoms as "Much Improved" or "Very Much Improved" 7
• Benefits of newer VMAT2 inhibitors (deutetrabenazine and valbenazine) over tetrabenazine include:
  • Less frequent dosing
  • Better tolerability
  • Minimal off-target binding 5
• Dosage considerations:
  • For CYP2D6 poor metabolizers, dosage reduction is recommended for valbenazine 6
  • Careful titration of VMAT2 inhibitors is required for optimal effect 1

Step 4: Alternative Pharmacological Options

• Beta-blockers may provide some relief, though evidence is limited 1
• Benzodiazepines have shown limited efficacy 1
• Tocopherol (vitamin E) has demonstrated effectiveness and is generally well-tolerated 4
• Ginkgo biloba, amantadine, clonazepam, and zolpidem have been used with varying success 5

Step 5: Advanced Interventions for Severe Cases

• Electroconvulsive therapy (ECT) should be considered only for severe cases where medications are ineffective or not tolerated, particularly in bipolar disorder 1
• Botulinum toxin injections or deep brain stimulation may be considered in refractory cases 5

Important Caveats and Pitfalls

• Anticholinergic medications: These have a limited and potentially problematic role in TD management as they may actually aggravate TD symptoms 1

  • Only use when TD coexists with drug-induced parkinsonism
  • Monitor for adverse effects such as mental confusion, visual hallucinations, urinary retention
  • Avoid in patients with angle-closure glaucoma and use with caution in elderly males with prostatic hypertrophy

• Misdiagnosis: Avoid confusing TD with:

  • Akathisia (often misdiagnosed as psychotic agitation or anxiety)
  • Withdrawal dyskinesia (occurs with cessation of neuroleptics but typically resolves) 1

• Monitoring requirements:

  • AIMS assessments every 3-6 months
  • Additional monitoring for specific medications (e.g., lithium levels, thyroid and renal function tests)
  • Body mass index monitoring if atypical antipsychotics are added 1