According to a commentary, until 2017, management of tardive dyskinesia was restricted to off-label treatments with insufficient evidence, such as tetrabenazine, a vesicular monoamine transporter-2 (VMAT-2) inhibitor. It notes that in April, 2017, valbenazine, a new-generation VMAT-2 inhibitor, was the first treatment to be approved by the US FDA for patients with tardive dyskinesia, based on one positive phase IIb and one phase III trial. Deutetrabenazine, a new VMAT-2 inhibitor, which is already approved in US for treatment of Huntington's chorea, is to be evaluated by the FDA for tardive dyskinesia in August, 2017.
The commentary highlights that the recent success of VMAT-2 inhibitors raises several questions:
• What differentiates patient subgroups regarding severity, persistence, and clinical effect of tardive dyskinesia, and their likelihood of response to VMAT-2 inhibitors?
• Which patient-based rating scales require development to sufficiently capture the individual burden of the disorder?
• Can VMAT-2 inhibitors prevent progression from early or subsyndromal signs to full or more severe dyskinesia?
• What is the time course of tardive dyskinesia in patients with and without long-term treatment with dopamine receptor antagonists who are receiving VMAT-2 inhibitors?
• What predicts successful discontinuation of VMAT-2 inhibitors after resolution of tardive dyskinesia?