What are the treatment options for breakthrough symptoms of tardive dyskinesia?

Treatment of Breakthrough Symptoms in Tardive Dyskinesia

For breakthrough symptoms of tardive dyskinesia, use FDA-approved VMAT2 inhibitors (valbenazine or deutetrabenazine) as first-line pharmacological treatment, as these are the only medications with strong evidence for efficacy in established TD. 1, 2

Initial Management Steps

When breakthrough symptoms occur despite current management:

• Gradually withdraw the offending antipsychotic if clinically feasible, as this remains the primary intervention when TD symptoms emerge or worsen 3, 4
• Switch to atypical antipsychotics with lower D2 affinity (clozapine or quetiapine) if discontinuation is not possible due to psychiatric instability 5
• Document baseline severity using the Abnormal Involuntary Movement Scale (AIMS) before initiating any new treatment 1, 2

Pharmacological Treatment for Breakthrough Symptoms

VMAT2 Inhibitors (First-Line)

Valbenazine (INGREZZA):

• Start at 40 mg once daily, increase to 80 mg once daily after one week based on response and tolerability 2
• Demonstrated mean reduction of 3.0-3.3 units on AIMS dyskinesia score compared to 0.1 units with placebo at 6 weeks 2
• Reduce dose to 40 mg daily in CYP2D6 poor metabolizers 2

Deutetrabenazine (AUSTEDO):

• Start at 12 mg per day, titrate upward in 6 mg increments weekly until satisfactory control is achieved, up to maximum 48 mg per day 1
• Demonstrated mean improvement of 3.2-3.3 units on AIMS total score versus 1.4 units with placebo at 12 weeks 1
• Average effective dose was 38-40 mg per day in clinical trials 1

Alternative Pharmacological Options

For mild breakthrough symptoms:

• Low-dose benzodiazepines (e.g., clonazepam) may reduce both dyskinesia and associated anxiety 6

For tardive dystonia specifically:

• Anticholinergic medications may be effective, unlike their lack of benefit in classic TD 6, 7
• Botulinum toxin injections for localized tardive dystonia (retrocollis, blepharospasm) 6, 7

Presynaptic dopamine depletors:

• Tetrabenazine or reserpine may have efficacy, especially in tardive dystonia, though side effects often limit use 6

Critical Considerations

• Avoid abrupt withdrawal of the offending antipsychotic, as this can cause exacerbation of tardive syndromes; taper gradually 7
• Do not use anticholinergics for classic TD, as they are unhelpful and may aggravate symptoms 6
• Clozapine may temporarily suppress TD symptoms but does not provide permanent resolution; symptoms can reemerge after discontinuation 8
• The concern over TD should not outweigh potential benefits of antipsychotics for patients who genuinely need these medications 3, 4

Monitoring Treatment Response

• Reassess AIMS scores every 3-6 months to track response to intervention 3, 4
• Continue regular monitoring even after symptom improvement, as TD may persist or recur 3, 4
• Document all treatment changes and their effects for ongoing management decisions 1, 2