What are the treatment options for Tardive Dyskinesia (TD)?

From the Guidelines

Tardive dyskinesia is best treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) for patients with moderate to severe or disabling symptoms associated with antipsychotic therapy. The American Psychiatric Association recommends this treatment approach 1. For established cases, FDA-approved VMAT2 inhibitors such as valbenazine and deutetrabenazine are effective treatments. These medications work by reducing dopamine release in the brain, which helps control the involuntary movements.

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

• Discontinuing the causative medication, typically antipsychotics, if possible
• Using the lowest effective dose of antipsychotics to minimize the risk of tardive dyskinesia
• Regular monitoring for early signs of tardive dyskinesia
• Individualizing treatment based on symptom severity, medication tolerability, and underlying psychiatric conditions
• Considering alternative treatments such as clonazepam, amantadine, or ginkgo biloba extract, though these have less evidence supporting their efficacy

It's also important to note that atypical antipsychotics generally carry a lower risk of tardive dyskinesia than typical antipsychotics 1. However, the primary recommendation for treatment of moderate to severe or disabling tardive dyskinesia remains the use of a reversible VMAT2 inhibitor, as stated by the American Psychiatric Association 1.

From the FDA Drug Label

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. 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

Treatment for Tardive Dyskinesia:

• Valbenazine (INGREZZA) is effective in treating tardive dyskinesia, with a statistically significant reduction in AIMS total dyskinesia score compared to placebo 2.
• Deutetrabenazine (AUSTEDO) is also effective in treating tardive dyskinesia, with a statistically significant improvement in AIMS total score compared to placebo 3. Key Points:
• Valbenazine and deutetrabenazine have been shown to be effective in reducing the symptoms of tardive dyskinesia.
• The Abnormal Involuntary Movement Scale (AIMS) was used to assess the severity of tardive dyskinesia in clinical trials.
• Both valbenazine and deutetrabenazine demonstrated statistically significant improvements in AIMS total scores compared to placebo.

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

VMAT2 Inhibitors

• Deutetrabenazine and valbenazine are novel VMAT2 inhibitors and the only drugs to receive approval from the US FDA for the treatment of tardive dyskinesia 5, 6
• These medications have demonstrated efficacy in several class 1 studies 6
• Deutetrabenazine has a recommended starting dose of 6 mg BID, administered with food, and can be increased at weekly intervals in increments of 6 mg/day to a maximum recommended daily dosage of 24 mg BID 7

Other Treatment Options

• Amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation are other treatment options for tardive dyskinesia, although their effectiveness and safety profiles may vary 5
• Treatment of tardive dyskinesia must be individualized and based on the severity, phenomenology, potential side effects, and other factors 5, 6

Efficacy and Safety of Deutetrabenazine

• Deutetrabenazine has been shown to be effective in reducing tardive dyskinesia symptoms, with a number needed to treat (NNT) of 5 (95% CI 3-19) and a number needed to harm (NNH) of 189 (not significant) 7
• The most common adverse reactions associated with deutetrabenazine were nasopharyngitis and insomnia, with NNH values of 50 (not significant) and 34 (95% CI 18-725), respectively 7