Another Medication for Tardive Dyskinesia

The FDA recently approved the vesicular monoamine transporter 2 (VMAT2) inhibitor valbenazine to treat tardive dyskinesia (TD; NEJM JW Psychiatry May 2017 and Am J Psychiatry 2017; 174:476). An industry-sponsored, Phase II/III multicenter, double-blind, placebo-controlled, 12-week trial has now examined another VMAT2 inhibitor. Deutetrabenazine is related to tetrabenazine, used off label for TD for over 30 years; contains deuterium, which attenuates metabolism and decreases plasma fluctuation; and is FDA-approved for chorea in Huntington disease (with a black-box warning about suicidality/depression).

The 117 participants had moderate-to-severe TD and were required to have TD for ≥3 months and to have taken dopamine antagonists for ≥3 months. Movement-disorder experts rated TD on videos with the Abnormal Involuntary Movement Scale (AIMS), the primary efficacy measure.

About half of the patients had schizophrenia (schizoaffective disorder, 19%; bipolar disorder, 23%). The medication was started at 12 mg/day and increased if necessary to 48 mg/day. At 12 weeks, deutetrabenazine was associated with a significant lower mean AIMS score, which became evident by week 4. However, treatment success (based on clinical global impression) was nonsignificantly greater with active medication than placebo (48% and 40%), and this remained true in patients with worse baseline AIMS scores (52% and 40%). Adverse events (including depression) were similar in both groups.