Review of deutetrabenazine: a novel treatment for chorea associated with Huntington's disease

Drug Des Devel Ther. 2018 Feb 15:12:313-319. doi: 10.2147/DDDT.S138828. eCollection 2018.

Abstract

Deutetrabenazine was recently approved for the treatment of chorea in Huntington's disease (HD) and is the first deuterated medication that has been US Food and Drug Administration (FDA)-approved for therapeutic use. In this article, we review deutetrabenazine's drug design, pharmacokinetics, drug interactions, efficacy, adverse events, comparison with tetrabenazine, dosage, and administration. Deutetrabenazine is a deuterated form of tetrabenazine and is a vesicular monoamine transporter 2 (VMAT2) inhibitor. The substitution of deuterium for hydrogen at key positions in the tetrabenazine molecule allows a longer drug half-life and less frequent daily dosing. Deutetrabenazine is administered twice daily up to a maximum daily dose of 48 mg, which corresponds to a similar daily dose of 100 mg of tetrabenazine. In a Phase III clinical trial (First-HD), there was a statistically significant improvement of chorea in HD subjects, as well as improvements in global impression of change as assessed by both patients and clinicians. This improvement was seen without significant adverse effects as the overall tolerability profile of deutetrabenazine was similar to placebo. Somnolence was the most commonly reported symptom in the deutetrabenazine group. In a study where subjects converted from tetrabenazine to deutetrabenazine in an open-label fashion (ARC-HD) and indirect comparison studies between tetrabenazine and deutetrabenazine, there is a suggestion that while efficacy for chorea is similar, the data may slightly favor tetrabenazine, but adverse effects and tolerability strongly favor deutetrabenazine. These data have not been replicated in true head-to-head studies. Current evidence supports that deutetrabenazine is an effective therapeutic treatment option for chorea in HD and may provide a more favorable adverse effect profile than tetrabenazine. However, more data are needed, particularly in the form of head-to-head studies between deutetrabenazine and other treatment options as well as longer term clinical experience with deutetrabenazine.

Keywords: Huntington’s disease; chorea; deutetrabenazine; tetrabenazine.

Publication types

  • Review

MeSH terms

  • Adrenergic Uptake Inhibitors / administration & dosage*
  • Adrenergic Uptake Inhibitors / adverse effects
  • Adrenergic Uptake Inhibitors / pharmacokinetics
  • Animals
  • Drug Administration Schedule
  • Drug Interactions
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / metabolism
  • Huntington Disease / physiopathology
  • Huntington Disease / psychology
  • Tetrabenazine / administration & dosage
  • Tetrabenazine / adverse effects
  • Tetrabenazine / analogs & derivatives*
  • Tetrabenazine / pharmacokinetics
  • Treatment Outcome
  • Vesicular Monoamine Transport Proteins / antagonists & inhibitors*
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Adrenergic Uptake Inhibitors
  • SLC18A2 protein, human
  • Vesicular Monoamine Transport Proteins
  • deutetrabenazine
  • Tetrabenazine