Title: Efficacy and Adverse Events of Tetrabenazine, Deutetrabenazine, and Valbenazine in Huntington’s Disease
Authors: Jorge Patino, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker, N. Rocha, Andrew Duker, and Erin Furr Stimming
Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea
Objective
To compare the efficacy and safety of tetrabenazine, deutetrabenazine, and valbenazine for chorea and neuropsychiatric outcomes in Huntington’s disease (HD).
Background
VMAT2 inhibitors are standard treatments for HD chorea, yet comparative data across agents remain limited. Randomized controlled trials (RCTs) of tetrabenazine, deutetrabenazine, and valbenazine provide measurable outcomes suitable for pooled evaluation.
Design/Methods
A meta‑analysis of PubMed‑indexed RCTs evaluating VMAT2 inhibitors in HD was performed. Outcomes included change in UHDRS‑Total Maximal Chorea (TMC), depression scores (HADS/HAM-D), Clinical Global Impression–Change (CGI‑C), and adverse events. Effect sizes were calculated using inverse‑variance models for continuous outcomes and Mantel‑Haenszel methods for dichotomous outcomes.
Results
Across 283 participants, VMAT2 inhibitors significantly improved UHDRS‑TMC (MD −2.97; 95% CI −3.72 to −2.21; I2 = 0%) [Figure 1]. CGI‑C response favored active treatment (RR 3.11; 95% CI 2.02–4.78) [Figure 2]. No significant worsening of depression scores was observed (SMD −0.19; 95% CI −0.43 to 0.05) [Figure 3]. Adverse‑event rates varied by agent: somnolence was more frequent with valbenazine and tetrabenazine (RR 5.11; 95% CI 1.98–13.19), while serious adverse events (RR 1.43; 95% CI 0.36–5.66), mortality (RR 0.73; 95% CI 0.09–5.81), fatigue (RR 2.16; 95% CI 1.00–4.65), akathisia (RR 2.17; 95% CI 0.61–7.64), rash (RR 3.17; 95% CI 0.88–11.34), and falls (RR 0.95; 95% CI 0.50–1.80) did not differ significantly from controls.
Conclusions
VMAT2 inhibitors provide comparable reductions in HD chorea with favorable safety and tolerability profiles. Neuropsychiatric domains showed no significant worsening. However, subtle differences in agent-specific efficacy, side effects, and dosing schedules suggest a need for head-to-head trials to better guide individualized therapy.
Citation
Patino J, Rissardo JP, Caprara AL, McGarry A, Walker I, Rocha N, Duker A, Furr Stimming E. Efficacy and Adverse Events of Tetrabenazine, Deutetrabenazine, and Valbenazine in Huntington’s Disease. Mov Disord 2026;41(Suppl_1):S434.
Figure 1. Forest plot of pooled MD of UHDRS‑Total Maximal Chorea.
Figure 2. Forest plot of pooled RR of CGI-C response.
Figure 3. Forest plot of pooled SMD of depressive outcomes.