Objective: To evaluate efficacy and safety of deutetrabenazine (DTB) in Huntington’s Disease (HD) in order to guide evidence-based clinical decisions.

Background: HD is a genetic neurodegenerative disorder marked by chorea and cognitive decline. Tetrabenazine (TBZ), a pioneering drug for HD, is effective but associated with adverse events (AEs) – sleep disturbances and parkinsonism. DTB, a second-generation drug, aims to reduce these AEs while maintaining efficacy.

Method: Research was conducted in PubMed, Cochrane, and Embase using the descriptors ‘Huntington disease’, ‘deutetrabenazine’ and equivalents. Two independent researchers reviewed titles and abstracts, excluding duplicates with Rayyan. Only clinical studies on the research question were included.

Results: From 154 articles, all of the 5 included work with data from First-HD (DTB, n=45; placebo, n=45) and ARC-HD (rollover, n=82; switch, n=37). In this scenario, DTB significantly reduced UHDRS (Unified Huntington’s Disease Rating Scale) total maximal chorea (TMC) scores, with mean reductions of -4.5 (±3.1) in rollover cohort patients (RC; those already treated with DTB) and -2.1 (±3.3) in switch cohort patients (SC; those converted overnight from a stable TBZ dose) at week (W) 8. Minimal change was observed from W8 to W145. A 30% or greater TMC reduction occurred in 74% of RC and 46% of SC at doses of 24–48 mg/day (Frank et al., 2025). Conversion from TBZ to DTB maintained TMC scores at W1 and had a significant mean reduction of 2.1 points at W8 (p < 0.001) (Frank et al., 2017). The UHDRS total motor score (TMS) decreased from baseline to W8 but increased from W8 to W145 (Frank et al., 2022). Safety analyses indicated that DTB was well tolerated, with AEs including falls (38% RC, 43% SC), depression (32%, 22%), anxiety (27%, 35%), insomnia (23%, 16%), somnolence (20%, 30%), and akathisia (6%, 11%). Less frequent AEs included suicidality (9%, 5%) and parkinsonism (4%, 8%) (Frank et al., 2022). Akathisia was more common with doses >48 mg/day, pointing to a dose-dependent relationship (Frank et al., 2025). Serious AEs were infrequent.

Conclusion:

DTB demonstrates to be safe and effective in reducing chorea in HD. Conversion from TBZ to DTB is effective and well-tolerated. These findings support DTB as a viable treatment option, although long-term studies are needed to confirm its benefits and safety over longer periods.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-deutetrabenazine-in-huntingtons-disease-a-systematic-review/