Tetrabenazine Versus Deutetrabenazine for Huntington's Disease: Twins or Distant Cousins?

Abstract

BackgroundTetrabenazine is the only US Food and Drug Administration‐approved drug for Huntington's disease, and deutetrabenazine was recently tested against placebo. A switching‐trial from tetrabenazine to deutetrabenazine is underway, but no head‐to‐head, blinded, randomized controlled trial is planned. Using meta‐analytical methodology, the authors compared these molecules.Methods RCTs comparing tetrabenazine or deutetrabenazine with placebo in Huntington's disease were searched. The authors assessed the Cochrane risk‐of‐bias tool, calculated indirect treatment comparisons, and applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.ResultsThe evidence network for this report comprised 1 tetrabenazine trial and 1 deutetrabenazine trial, both against placebo. Risk of bias was moderate in both. Participants in the tetrabenazine and deutetrabenazine trials did not differ significantly on motor scores or adverse events. Depression and somnolence scales significantly favored deutetrabenazine.ConclusionThere is low‐quality evidence that tetrabenazine and deutetrabenazine do not differ in efficacy or safety. It is important to note that these results are likely to remain the only head‐to‐head comparison between these 2 compounds in Huntington's disease.

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

“…The efficacy of deutetrabenazine vs tetrabenazine in treating HD-associated chorea was recently evaluated by comparing First-HD and TETRA-HD trials. 17 In this comparison, deutetrabenazine and tetrabenazine had mild effects on chorea when compared with placebo, but neither differed significantly when compared with each other. The actual UHDRS point reduction was higher in TETRA-HD (5 points) than in First-HD (4.4 points), but the amount of change that occurred when compared with placebo was not different when comparing the two studies.…”

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

“…Outcome measures were the parkinsonism items of the UHDRS scale and the UPDRS [48]. However, some methodologic concerns have been raised regarding published post-hoc comparisons with TBZ [49].…”

Deutetrabenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

“…Tetrabenazine has been used “off‐label” for the treatment of TD . Comparing deutetrabenazine with tetrabenazine for the treatment of TD using meta‐analytic techniques is not possible as there are no randomised placebo‐controlled studies of tetrabenazine for TD; however, in an indirect comparison of deutetrabenazine and tetrabenazine for Huntington's disease, tetrabenazine and deutetrabenazine did not differ significantly on motor scores or adverse events, but depression and somnolence scales favoured deutetrabenazine significantly . Another indirect analysis comparing tolerability of deutetrabenazine and tetrabenazine in Huntington's disease demonstrated that deutetrabenazine was associated with a significantly lower risk of moderate to severe adverse events and neuropsychiatric adverse events including agitation, akathisia, depression, depression/agitated depression, drowsiness/somnolence, insomnia and parkinsonism; deutetrabenazine also had a significantly lower rate of dose reduction or dose reduction/suspension …”