Treatment for Tardive Dyskinesia
For patients with moderate to severe or disabling tardive dyskinesia, treat with a VMAT2 inhibitor (valbenazine or deutetrabenazine) as first-line pharmacotherapy. 1
Initial Management Steps
If clinically feasible, gradually withdraw or reduce the offending antipsychotic medication as this represents the most fundamental intervention. 2, 3 However, for most patients with serious mental illness requiring ongoing antipsychotic therapy, complete discontinuation is not possible due to risk of psychiatric relapse. 4
If antipsychotic therapy must continue, switch from a first-generation to a second-generation antipsychotic with lower D2 receptor affinity (specifically clozapine or quetiapine), as this may reduce tardive dyskinesia symptoms. 2, 3, 4
Pharmacological Treatment with VMAT2 Inhibitors
Deutetrabenazine (FDA-Approved)
Deutetrabenazine demonstrates robust efficacy in class 1 studies and is FDA-approved specifically for tardive dyskinesia treatment. 2, 5
Dosing protocol:
- Start at 12 mg per day 5
- Titrate upward at weekly intervals in 6 mg increments 5
- Continue titration until satisfactory control of dyskinesia is achieved, intolerable side effects occur, or maximum dose of 48 mg per day is reached 5
- Average effective dose is approximately 38-40 mg per day 5
- Administer twice daily with food 6
Clinical efficacy data:
- AIMS total score improved by 3.2-3.3 units compared to 1.4 units with placebo at 12 weeks 5
- Treatment effects are sustained during maintenance therapy 5
- Symptoms return toward baseline within 1 week of discontinuation 5
Key considerations for deutetrabenazine:
- Consider CYP2D6 modulators for drug-drug interactions 6
- Contraindicated in hepatic impairment 6
- Requires dose titration to efficacy/tolerability 6
Valbenazine (FDA-Approved Alternative)
Valbenazine is equally efficacious and offers different practical advantages. 4, 6, 7
Dosing differences:
- Once daily administration (versus twice daily for deutetrabenazine) 6
- Titrate to target dose of 80 mg/day 6
- No food requirement 6
- Consider both CYP2D6 and CYP3A4 modulators for drug interactions 6
Mechanism of Action
VMAT2 inhibitors reduce dopamine packaging into synaptic vesicles, leading to decreased dopamine release in the motor striatum, which provides robust therapeutic effects by reducing excessive "go" signaling and increasing "stop" signaling. 8, 9
Monitoring Requirements
Before initiating any antipsychotic therapy, record baseline assessment of abnormal movements. 2, 3
Perform regular monitoring for dyskinesias at least every 3-6 months using the Abnormal Involuntary Movement Scale (AIMS). 2, 3 Early detection is crucial as tardive dyskinesia may persist even after medication discontinuation. 2, 3
Common Pitfalls to Avoid
Do not use anticholinergic medications for tardive dyskinesia - these are indicated for acute dystonia and parkinsonism, not tardive dyskinesia. 1
Do not avoid antipsychotics entirely in patients who genuinely need them due to fear of tardive dyskinesia - the concern over tardive dyskinesia should not outweigh potential benefits for patients requiring antipsychotic therapy. 2, 3
Avoid long-term metoclopramide use in any patient at risk for tardive dyskinesia, as it can cause potentially irreversible tardive dyskinesia, particularly in elderly patients. 2
Prevention Strategies
Use atypical antipsychotics when possible as they carry lower tardive dyskinesia risk compared to typical antipsychotics. 2, 3
Prescribe antipsychotics only for specific indications, use the minimum effective dose, and minimize duration of therapy. 4
Obtain adequate informed consent regarding tardive dyskinesia risk when prescribing antipsychotics. 2