VMAT2 Inhibitors for Tardive Dyskinesia—Practice Implications

Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively. These agents were pharmacologically modified from tetrabenazine, a VMAT2 inhibitor used off-label in the treatment of tardive dyskinesia. Despite FDA-labeled indications of deutetrabenazine and valbenazine, each agent was explored as a treatment option for those with tardive dyskinesia. In this study, the pharmacologic modifications of the 2 new VMAT2 inhibitors are described, with detailed explanation as to how these may impact clinical practice. The associated case series, observational studies, and clinical trials exploring their use in the treatment of tardive dyskinesia are reported with expert opinion on practice implication.