What are the treatment options for tardive dyskinesia?

From the Guidelines

Treatment of tardive dyskinesia should prioritize the use of reversible inhibitors of the vesicular monoamine transporter 2 (VMAT2), such as valbenazine or deutetrabenazine, as recommended by the American Psychiatric Association 1. The goal of treatment is to reduce the severity of involuntary movements while minimizing the risk of worsening the underlying psychiatric condition.

• The first step in managing tardive dyskinesia is to reduce or discontinue the causative medication, typically an antipsychotic or metoclopramide, if possible, while carefully monitoring for withdrawal symptoms or worsening of the underlying condition 1.
• For patients still requiring antipsychotic medication, switching to a lower-risk atypical antipsychotic like quetiapine or clozapine may help, as suggested by the American Academy of Child and Adolescent Psychiatry 1.
• VMAT2 inhibitors, such as valbenazine (Ingrezza, 40-80 mg daily) and deutetrabenazine (Austedo, 6-48 mg daily in divided doses), are specifically designed to treat tardive dyskinesia by regulating dopamine release in the brain.
• Other options, including older medications like tetrabenazine, clonazepam, or amantadine, and Ginkgo biloba extract (240 mg daily), have less evidence supporting their use but may be considered in certain cases.
• Treatment response should be monitored using standardized rating scales, and patients should be aware that improvement may take several weeks to become noticeable. The American Psychiatric Association recommends (1B) that patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) 1.

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 A randomized, double-blind, placebo-controlled trial of INGREZZA was conducted in patients with moderate to severe tardive dyskinesia as determined by clinical observation. 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 options for tardive dyskinesia include:

• Deutetrabenazine (AUSTEDO):
  • Doses of 24 mg and 36 mg per day demonstrated statistically significant improvement in AIMS total score compared to placebo 2
  • Treatment duration included a 4-week dose escalation period and an 8-week maintenance period followed by a 1-week washout
• Valbenazine (INGREZZA):
  • A dose of 80 mg per day demonstrated statistically significant improvement in AIMS total dyskinesia score compared to placebo 3
  • Treatment duration included a 6-week dose titration period and a 6-week maintenance period followed by a 4-week period off-drug

From the Research

Treatment Options for Tardive Dyskinesia

Tardive dyskinesia is a movement disorder characterized by irregular, stereotyped, and choreiform movements associated with the use of antipsychotic medication. The primary goal is to prevent tardive dyskinesia by following best practices for prescribing antipsychotic medication, including limiting prescription to specific indications, using the minimum effective dose, and minimizing the duration of therapy 4.

First-Line Management

The first-line management of tardive dyskinesia is the withdrawal of antipsychotic medication if clinically feasible. However, for many patients with serious mental illness, discontinuation of antipsychotics is not possible due to disease relapse 4.

Alternative Treatment Options

Some alternative treatment options include:

• Switching from a first-generation to a second-generation antipsychotic with a lower D2 affinity, such as clozapine or quetiapine, which may be effective in reducing tardive dyskinesia symptoms 4.
• Using vesicular monoamine transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, which have demonstrated efficacy in several class 1 studies 5, 6, 7, 8.
• Valbenazine and deutetrabenazine offer a unique mechanism of action and have been approved by the FDA for the treatment of tardive dyskinesia 5, 6, 7, 8.

Key Considerations

When using VMAT2 inhibitors, key considerations include:

• Dosing and administration: valbenazine is administered once daily, while deutetrabenazine is administered twice daily 8.
• Titration requirements: deutetrabenazine requires dose titration to efficacy/tolerability, while valbenazine is titrated to a target dose of 80 mg/day 8.
• Drug-drug interactions: both valbenazine and deutetrabenazine have potential interactions with other medications, including CYP2D6 and CYP3A4 modulators 8.
• Adverse event profile: both valbenazine and deutetrabenazine have similar adverse event profiles, but with some minor differences 8.