What is the treatment protocol for Tardive Dyskinesia (TD)?

From the Guidelines

The primary treatment for tardive dyskinesia involves discontinuing or reducing the causative medication, typically antipsychotics, when clinically feasible, and using FDA-approved VMAT2 inhibitors, such as valbenazine or deutetrabenazine, as first-line treatments for symptomatic management. According to the American Psychiatric Association practice guideline for the treatment of patients with schizophrenia 1, 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). The use of VMAT2 inhibitors has been shown to be effective in reducing the symptoms of tardive dyskinesia, and they are considered a first-line treatment option.

Some key points to consider when treating tardive dyskinesia include:

• Discontinuing or reducing the causative medication, typically antipsychotics, when clinically feasible
• Using FDA-approved VMAT2 inhibitors, such as valbenazine (40-80 mg once daily) or deutetrabenazine (6-48 mg/day in divided doses), as first-line treatments for symptomatic management
• Alternative options, such as clonazepam (0.5-4 mg/day), amantadine (100-400 mg/day), or ginkgo biloba extract (240 mg/day), may be considered, although they have less robust evidence
• Treatment should be individualized based on symptom severity, medication tolerability, and comorbidities
• Regular monitoring for improvement using standardized rating scales, such as the Abnormal Involuntary Movement Scale (AIMS), is essential, as is watching for side effects, such as somnolence, depression, or parkinsonism, with VMAT2 inhibitors 1.

Prevention strategies are also crucial in managing tardive dyskinesia, and include:

• Using the lowest effective dose of antipsychotics
• Considering atypical over typical antipsychotics
• Regular screening for early movement disorders in at-risk patients
• Monitoring for dyskinesias at least every 3 to 6 months, using a standardized measure, such as the AIMS 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 In Study 1, a 12-week, placebo-controlled, fixed-dose trial, adults with tardive dyskinesia were randomized 1:1:1:1 to 12 mg AUSTEDO, 24 mg AUSTEDO, 36 mg AUSTEDO, or placebo The dose of AUSTEDO was started at 12 mg per day and increased at weekly intervals in 6 mg/day increments to a dose target of 12 mg, 24 mg or 36 mg per day. In Study 2, a 12-week, placebo-controlled, flexible-dose trial, adults with tardive dyskinesia (n=113) received daily doses of placebo or AUSTEDO, starting at 12 mg per day with increases allowed in 6-mg increments at 1-week intervals until satisfactory control of dyskinesia was achieved, until intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached

The treatment protocol for tardive dyskinesia involves:

• Starting with a dose of 12 mg per day of deutetrabenazine (AUSTEDO)
• Increasing the dose at weekly intervals in 6 mg/day increments
• Target doses of 12 mg, 24 mg, or 36 mg per day
• Alternatively, using a flexible-dose regimen with increases allowed in 6-mg increments at 1-week intervals until satisfactory control of dyskinesia is achieved, or until a maximal dose of 48 mg per day is reached 2 Alternatively, valbenazine (INGREZZA) can be used at a dose of 40 mg or 80 mg per day 3

From the Research

Treatment Options for Tardive Dyskinesia

The treatment protocol for tardive dyskinesia (TD) involves several options, including:

• Prevention of TD by limiting the use of antipsychotic medications and using the minimum effective dose 4
• Withdrawal of offending medications, if clinically feasible 4
• Switching from a first-generation to a second-generation antipsychotic with a lower D2 affinity, such as clozapine or quetiapine 4
• Use of vesicular monoamine transporter 2 (VMAT2) inhibitors, such as tetrabenazine, deutetrabenazine, and valbenazine, which are considered the treatment of choice for most patients with TD 5, 6
• Other treatment options, including amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation 5, 7

VMAT2 Inhibitors

VMAT2 inhibitors, such as deutetrabenazine and valbenazine, have been shown to be effective in reducing TD symptoms 6, 8. These medications work by depleting presynaptic dopamine and reducing involuntary movements. The advantages of VMAT2 inhibitors include:

• High affinity for VMAT2 and minimal off-target binding 5
• Less frequent dosing and better tolerability compared to tetrabenazine 5
• No association with the development of TD, unlike dopamine receptor-blocking agents (DRBAs) 5

Efficacy and Safety of Valbenazine

Valbenazine has been shown to be effective in reducing TD symptoms, with a number needed to treat (NNT) of 4 (95% CI 3-6) 8. The most common adverse event associated with valbenazine is somnolence, with a number needed to harm (NNH) of 15 (95% CI 9-52) 8. Valbenazine is currently the only US Food and Drug Administration-approved agent specifically indicated for the treatment of TD.

Treatment Algorithm

A suggested treatment algorithm for TD includes:

• Prevention and early recognition of TD
• Withdrawal of offending medications, if clinically feasible
• Use of VMAT2 inhibitors, such as deutetrabenazine and valbenazine, as first-line treatment
• Consideration of other treatment options, such as amantadine, clonazepam, and botulinum toxin, if VMAT2 inhibitors are not effective or tolerated 7