New Class of VMAT2 Inhibitors Approved for the Treatment of Tardive Dyskinesia

A new class of vesicular monoamine transporter 2 inhibitors (VMAT2 inhibitors) approved for the treatment of Tardive Dyskinesia (TD), a dyskinesia that most commonly emerges after long-term use of dopamine receptor blocking drugs, show efficacious results, according to a recent presentation at Neurology Week.

Rajeev Kuman, MD, FRCPC, Director, Rocky Mountain Movement Disorders Center, Huntington’s Disease Society of America Center of Excellence, Colorado Neurological Institute, Englewood, CO, discussed updated treatments and recommendations for quality of life improvement in patients with TD.

“Our goal of treatment in tardive dyskinesia is, first of all, to maintain psychiatric stability, because in general the main thing that is of concern in these individuals is the psychiatric problem, and the movement disorder problem is secondary,” Dr Kuman said. “We want to treat patients to improve tardive dyskinesia without overtreating them.”

Overtreating to remove all TD causes a likeliness of drug-induced parkinsonism or a degree of sedation. Dr Kuman recommended avoiding medications that worsen TD, including anticholinergics, which can heighten chorea and stereotypy.

The presentation provided an overview of medications historically used for the treatment of TD, including benzodiazepine and ginkgo biloba, which have little evidence to support their efficacy for the treatment of TD. Newer generation VMAT2 inhibitors, including FDA-approved valbenazine and deutetrabenazine, have more proven cases of effectiveness. Additionally, tetrabenazine is FDA approved for the treatment of chorea in Huntingtons disease and is in clinical trials for the treatment of TD.

Updated recommendations from the American Academy of Neurology suggest that the new generation VMAT2 inhibitors must be recommended as a treatment for patients with TD; followed by benzodiazepine and ginkgo biloba, which should be considered as a treatment; and antiparkinsonian agents, early-approved VMAT2 inhibitors, and pallidal deep brain stimulation that might be considered as a treatment. Withdrawing causative agents or switching from typical to atypical DRBA has insufficient evidence of effectiveness.

Short- and long-term efficacy for valbenazine and deutetrabenazine for the treatment of TD is positive. Controlled Phase 3 trials for these treatments showed significant improvement on the AIMS Severity Score.

There are no head-to-head studies to compare these 2 treatment options. Dr Kumar suggests customizing treatment options to the patient. Valbenazine is a once-daily treatment option, and side-effect profiles should be considered per patient.

Many patients with TD have additional diagnoses such as bipolar disorder and schizophrenia. Studies show that VMAT2 Inhibitors for the treatment of TD can be used in addition to continued use of an antipsychotic medication to maintain psychiatric stability.

“In these studies, about 75% of the patients were on and continued to take antipsychotics while the VMAT2 inhibitor was administered,” Dr Kumar said. “It’s OK to continue the antipsychotic, it’s also OK to continue other mood stabilizers.”

Additionally, more than half of the patients in these studies continued the use of antidepressants.

“The new treatments we have are highly efficacious and have a really good body of evidence supporting their use,” Dr Kumar concluded.

-Erin McGuinness

Reference

Kumar, R. Tardive Dyskinesia Across the Complexity Spectrum – From Quality of Life Improvement to Novel Treatments. Presented at Neurology Week 2021; July 14-18. Virtual.