Efficacy and Safety of VMAT2 Inhibitors in the Treatment of Huntington Disease: A Meta-Analysis of Randomized Clinical Trials.

Background and Objectives: Vesicular monoamine transporter 2 inhibitors (VMAT2is) have demonstrated effectiveness in attenuating motor symptoms of Huntington disease (HD). However, evidence regarding their long-term safety and overall efficacy in this population remains limited. The aim of this study was to investigate the efficacy and safety of VMAT2is in the treatment of HD. Methods: We performed a meta-analysis of placebo-controlled, randomized controlled trials (RCTs) of VMAT2is in patients with HD. PubMed, Embase, and Cochrane databases were searched for trials up to February 8, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Binary end points were compared using odds ratios (ORs) while continuous end points were compared using mean difference (MD) and standardized MD (SMD), with 95% CIs for all measures. The analysis end points included changes in the Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC), improvements in the Clinical Global Impression of Change (CGI-C), incidence of adverse effects, and alterations in depression scale scores. Results: Of 336 database results, 3 RCTs and 302 patients were included; 163 (53.97%) received VMAT2is. The UHDRS-TMC (MD -2.98; 95% CI [-4.21 to -1.75]; p = 0.009; I 2 = 0%) and CGI-C (OR 5.36; CI 95% [2.94-9.76]; p = 0.007; I 2 = 0%) scores were significantly improved in the intervention group. In addition, the therapy did not influence the adverse effects (OR 1.89; CI 95% [0.47-7.70]; p = 0.19 I 2 = 28%) and depression scale scores (SMD -0.40; 95% CI [-1.20 to 0.41]; p = 0.17; I 2 = 59%). Discussion: In patients with HD, treatment with VMAT2is improved chorea (UHDRS-TMC and CGI-C), with no significant changes in adverse effects or depressive symptoms. These findings indicate that VMAT2is may be a promising and safe treatment option for the disease.