What class of drugs treats tardive dyskinesia?

VMAT2 Inhibitors Are the Drug Class That Treats Tardive Dyskinesia

For moderate to severe or disabling tardive dyskinesia, VMAT2 inhibitors (valbenazine or deutetrabenazine) are the first-line pharmacotherapy and the only FDA-approved drug class specifically for this condition. 1, 2, 3

Mechanism and FDA-Approved Agents

• VMAT2 (vesicular monoamine transporter 2) inhibitors work by depleting presynaptic dopamine, reducing involuntary movements by decreasing transport of monoamines into presynaptic vesicles 4, 5

• Two FDA-approved VMAT2 inhibitors are available:

  • Valbenazine (INGREZZA) - dosed once daily, no food requirement 2, 5
  • Deutetrabenazine (AUSTEDO) - dosed twice daily, must be taken with food 3, 5

Clinical Efficacy and Evidence Quality

• Both agents demonstrated efficacy in well-designed class 1 clinical trials, representing the first FDA-approved medications specifically for tardive dyskinesia 1, 5

• These VMAT2 inhibitors have a major advantage over dopamine receptor-blocking agents: they do not cause tardive dyskinesia themselves 4

• No head-to-head studies exist comparing valbenazine versus deutetrabenazine, but both show similar efficacy profiles 4, 5

Practical Prescribing Differences

Valbenazine:

• Once-daily dosing 5
• Titrate to target dose of 80 mg/day 5
• Consider both CYP2D6 and CYP3A4 drug interactions 5
• No food requirements 5

Deutetrabenazine:

• Twice-daily dosing 5
• Dose titrate to efficacy/tolerability 5
• Must be administered with food 5
• Consider CYP2D6 modulators 5
• Contraindicated in hepatic impairment 5

Alternative Treatments (Not First-Line)

• Anticholinergic medications should NOT be used for tardive dyskinesia - they are indicated for acute dystonia and parkinsonism, not TD 1

• Other options with less robust evidence include amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation 4

Critical Management Context

• If antipsychotic therapy must continue, consider switching to clozapine, which has the lowest risk profile for movement disorders among all antipsychotics 1

• If clinically feasible, gradually withdraw the offending antipsychotic medication before or concurrent with VMAT2 inhibitor initiation 1, 6

• The majority of patients do not achieve complete remission with VMAT2 inhibitors, and TD may recur once treatment is withdrawn, making prevention still crucial 7