From the Guidelines
Tardive dyskinesia is best managed through a combination of prevention, medication adjustment, and targeted treatments, with a focus on discontinuing or reducing the causative agent and using FDA-approved VMAT2 inhibitors as the most effective pharmacological treatments. The first step is to discontinue or reduce the causative agent, typically antipsychotic medications, when clinically feasible 1. For patients who require continued antipsychotic therapy, switching to a second-generation antipsychotic with lower risk (such as quetiapine or clozapine) is recommended 1. FDA-approved VMAT2 inhibitors, including valbenazine, deutetrabenazine, and tetrabenazine, are the most effective pharmacological treatments, as recommended by the American Psychiatric Association 1. These medications work by reducing dopamine release in the brain, directly addressing the underlying mechanism of tardive dyskinesia.
Key Considerations
- Regular monitoring using standardized rating scales like the Abnormal Involuntary Movement Scale (AIMS) is essential to track symptom progression and treatment response 1.
- Early intervention is crucial, as tardive dyskinesia can become permanent if not addressed promptly.
- Patients should be educated about the condition and potential side effects of VMAT2 inhibitors, which may include somnolence, depression, and parkinsonism.
Treatment Options
- Valbenazine (40-80 mg daily)
- Deutetrabenazine (12-48 mg daily in divided doses)
- Tetrabenazine (25-200 mg daily in divided doses) It is essential to note that the American Psychiatric Association recommends treating patients with moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy 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 In Study 2, AIMS total score for patients receiving AUSTEDO demonstrated statistically significant improvement by 3.0 units from baseline to endpoint (Week 12), compared with 1.6 units in the placebo group with a treatment effect of -1. 4 units
Tardive Dyskinesia Management:
- The best management for tardive dyskinesia is treatment with deutetrabenazine (AUSTEDO) as it has shown statistically significant improvement in AIMS total score compared to placebo in two 12-week trials.
- Deutetrabenazine can be initiated at a dose of 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.
- The treatment response rate distribution and mean changes in the AIMS total score by visit can be used to assess the efficacy of deutetrabenazine in managing tardive dyskinesia 2.
From the Research
Management of Tardive Dyskinesia
The management of tardive dyskinesia (TD) involves several strategies, including:
- Preventing TD by following best practices for prescribing antipsychotic medication, such as limiting the prescription to specific indications, using the minimum effective dose, and minimizing the duration of therapy 3
- Withdrawing antipsychotic medication if clinically feasible, as this is the first-line management of TD 3, 4
- 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 TD symptoms 3
- Using vesicular monoamine transporter 2 (VMAT2) inhibitors, such as deutetrabenazine and valbenazine, which have demonstrated efficacy in several class 1 studies 5
Treatment Options
Other treatment options for TD include:
- Benzodiazepines, such as clonazepam, which may reduce the amount of dyskinesia and associated anxiety 4
- Anticholinergic drugs, which may be effective in tardive dystonia, but may aggravate TD 4
- Botulinum toxin injections, which are of considerable value in managing localized forms of tardive dystonia, such as retrocollis or blepharospasm 4, 6
- Deep brain stimulation and repetitive transcranial magnetic stimulation, which are newer approaches that have shown preliminary evidence of effectiveness 7
Considerations
When managing TD, it is essential to consider the individual patient's symptoms, etiology, and potential side effects of medications to find the best possible treatment approach 5. Additionally, early recognition and assessment of TD are crucial, as well as a comprehensive approach to management, including non-pharmacological interventions and lifestyle modifications 7.