Another Medication for Tardive Dyskinesia

Summary and Comment |
May 8, 2017

Another Medication for Tardive Dyskinesia

  1. Jonathan Silver, MD

Deutetrabenazine reduces abnormal movements and is well tolerated.

  1. Jonathan Silver, MD

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.


In the mid-1980s, I was the contact person at Hoffmann–La Roche for compassionate use of tetrabenazine. It is difficult to compare this study, which showed a strong placebo response, with the valbenazine study. The difference on AIMS between deutetrabenazine and placebo was −1.4, compared with −3.1 in the valbenazine study. Comparing actual study data on both drugs and tetrabenazine to determine any differential benefit would be valuable. The good news is that effective medications for TD should soon be available.

Editor Disclosures at Time of Publication

  • Disclosures for Jonathan Silver, MD at time of publication Royalties Textbook of Traumatic Brain Injury, 2nd edition Editorial boards UpToDate; Journal of Neuropsychiatry and Clinical Neuroscience; Journal of Neurology, Neurosurgery, and Psychiatry Leadership positions in professional societies North American Brain Injury Association (Board Member); Chair of Data Monitoring Safety Board for National Institute on Disability, Independent Living, and Rehabilitation Research study of donepezil on cognition after traumatic brain injury


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