What is the treatment for Tardive Dyskinesia (TD)?

From the Guidelines

Tardive dyskinesia is best treated by first discontinuing the causative medication, if possible, and then using FDA-approved VMAT2 inhibitors, such as valbenazine or deutetrabenazine, as the most effective options for symptomatic treatment. The treatment of tardive dyskinesia should prioritize reducing the severity and impact of movements on daily functioning, as complete symptom resolution may not occur 1. According to the American Psychiatric Association practice guideline for the treatment of patients with schizophrenia, patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy should be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) 1.

Some key points to consider in the treatment of tardive dyskinesia include:

• Discontinuing the causative medication, typically antipsychotics or certain antiemetics, if possible
• Using FDA-approved VMAT2 inhibitors, such as valbenazine (Ingrezza) 40-80mg once daily or deutetrabenazine (Austedo) 6-48mg daily in divided doses, as the most effective options for symptomatic treatment
• Considering alternative treatments, such as clonazepam 0.5-2mg daily, ginkgo biloba 240mg daily, or amantadine 100-300mg daily, for patients who cannot tolerate or access VMAT2 inhibitors
• Continuing treatment long-term, as tardive dyskinesia often persists even after stopping the causative medication
• Regularly monitoring for improvement using standardized rating scales, with dose adjustments as needed 1.

It is essential to note that early intervention typically yields better outcomes, as tardive dyskinesia can become permanent if left untreated for extended periods 1. Therefore, prompt treatment with VMAT2 inhibitors is recommended for patients with moderate to severe or disabling tardive dyskinesia.

From the FDA Drug Label

The efficacy of AUSTEDO in the treatment for tardive dyskinesia was established in two 12‑week, randomized, double-blind, placebo-controlled, multi-center trials conducted in 335 adult ambulatory patients with tardive dyskinesia caused by use of dopamine receptor antagonists The Abnormal Involuntary Movement Scale (AIMS) was the primary efficacy measure for the assessment of tardive dyskinesia severity In Study 1, the AIMS total score for patients receiving AUSTEDO demonstrated statistically significant improvement, from baseline to Week 12, of 3.3 and 3.2 units for the 36 mg and 24 mg arms, respectively, compared with 1. 4 units in placebo The change from baseline in the AIMS total dyskinesia score in the 80 mg INGREZZA group was statistically significantly different from the change in the placebo group.

Treatment of Tardive Dyskinesia:

• Deutetrabenazine (AUSTEDO) is effective in treating tardive dyskinesia, with significant improvements in AIMS total score compared to placebo 2.
• Valbenazine (INGREZZA) is also effective in treating tardive dyskinesia, with significant improvements in AIMS total score compared to placebo 3.
• The recommended dosage for deutetrabenazine is 12-48 mg per day, titrated upward at weekly intervals until satisfactory treatment of dyskinesia is achieved or until intolerable side effects occur 2.
• The recommended dosage for valbenazine is 40-80 mg per day, with a starting dose of 40 mg per day and titration upward at weekly intervals until satisfactory treatment of dyskinesia is achieved or until intolerable side effects occur 3.

From the Research

Treatment Options for Tardive Dyskinesia

• The first-line management of tardive dyskinesia is the withdrawal of antipsychotic medication if clinically feasible 4
• Switching from a first-generation to a second-generation antipsychotic with a lower D2 affinity, such as clozapine or quetiapine, may be effective in reducing tardive dyskinesia symptoms 4
• The strongest evidence for a suitable co-intervention to treat tardive dyskinesia comes from tests with the new VMAT inhibitors, deutetrabenazine and valbenazine 4, 5, 6, 7, 8

Vesicular Monoamine Transporter 2 Inhibitors

• VMAT2 inhibitors, including tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice for most patients with tardive dyskinesia 5
• Deutetrabenazine and valbenazine have pharmacokinetic advantages that translate into less frequent dosing and better tolerability compared to tetrabenazine 5
• Valbenazine and deutetrabenazine were recently approved by the FDA for the treatment of tardive dyskinesia 6, 7, 8

Efficacy and Tolerability of VMAT2 Inhibitors

• Valbenazine 40-80 mg and deutetrabenazine 12-36 mg per day have been evaluated for the treatment of tardive dyskinesia, with Abnormal Involuntary Movement Scale (AIMS) scores declining similarly (by 2-5 points) with use of either agent 8
• AIMS response rates, defined by a 50% decline in symptoms, range from 33% to 50% 8
• Both agents are well tolerated, with somnolence and akathisia reported most frequently (at low rates) 8