SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1637577
Efficacy and safety of vesicular monoamine transporter 2 inhibitors for Huntington's disease chorea based on network meta-analysis
Provisionally accepted
- Bishan hospital of Chongqing Medical University, Chongqing, China
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Objective: A Bayesian network meta-analysis was conducted to evaluate the efficacy, tolerability, and safety of vesicular monoamine transporter 2 (VMAT2) inhibitors in Huntington's disease chorea. Methods: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from January 1970 to January 2025 for eligible randomized controlled trials. Three VMAT2 inhibitors, including tetrabenazine, deutetrabenazine and valbenazine were investigated. The network meta-analysis was conducted based on a Bayesian framework using a fixed-effects model. As there were no closed loops in the network plot, comparisons of these interventions were directly formed by a consistency model. Results: Three randomized controlled trials (n = 299 patients) were included in the analysis. The surface under the cumulative ranking curve indicated that tetrabenazine was associated with the greatest improvement in the Unified Huntington's Disease Rating Scale Total Maximal Chorea score (0.878), followed by valbenazine (0.700) and deutetrabenazine (0.422). Meanwhile, in the Unified Huntington's Disease Rating Scale Total Motor score, valbenazine ranked highest, with a score of 0.781. Deutetrabenazine ranked highest in terms of overall withdrawals (0.800) and adverse events (AEs) (0.688), while valbenazine ranked first in withdrawals due to AEs (0.735), serious adverse events (0.807), as well as in reducing both suicide (0.683) and suicidal ideation (0.748). Conclusions: This study suggests that three VMAT2 inhibitors are effective in ameliorating chorea symptoms in patients with Huntington's disease. Tetrabenazine is the most effective in controlling chorea, whereas valbenazine may be the optimal choice for patients with comorbid psychiatric symptoms. The study protocol was registered in PROSPERO (CRD420251012431) before data extraction commenced (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251012431).
Keywords: Huntington's disease, Chorea, VMAT2 inhibitors, Tetrabenazine, Deutetrabenazine, valbenazine, Network meta-analysis
Received: 29 May 2025; Accepted: 09 Sep 2025.
Copyright: © 2025 Huang, Chen, Wen, Tao, Meng, Chen and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Changqing Zhou, Bishan hospital of Chongqing Medical University, Chongqing, China
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