{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:27:34Z","timestamp":1793482054216,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Huntington\u2019s disease (HD) causes progressive motor dysfunction, with chorea as its hallmark symptom. Vesicular monoamine transporter 2 (VMAT 2) inhibitors (tetrabenazine, deutetrabenazine, valbenazine) are established symptomatic therapies, while dopamine stabilizers (pridopidine, ordopidine) are emerging therapies, but their net benefit and safety remain uncertain. Methods: Seven databases were searched through May 2025 following PRISMA guidelines. Random effects meta-analyses calculated mean differences (MDs) for the Unified Huntington Disease Rating Scale total motor score (UHDRS TMS) and total maximal chorea score (TMC), plus risk ratios (RRs) for adverse events (AEs). Trial Sequential Analysis (TSA) applied a Lan DeMets O\u2019Brien Fleming \u03b1 spending function with 80% power. Results: Seven randomized trials (1431 participants) met inclusion criteria. VMAT 2 inhibitors significantly improved motor outcomes versus placebo (UHDRS TMS: MD \u22123.80, 95% CI \u22125.76 to \u22121.83; TMC: MD \u22123.05, 95% CI \u22123.84 to \u22122.26; both I2 = 0%). Dopamine stabilizers produced no meaningful change (UHDRS TMS: MD \u22120.98, 95% CI \u22122.48 to 0.51; I2 = 32%). Neither class increased total AEs (VMAT 2: RR 1.21, 95% CI 0.99 to 1.48; dopamine stabilizers: RR 1.05, 95% CI 0.92 to 1.20; both I2 = 0%). TSA confirmed robust evidence for VMAT 2 benefits on TMC but indicated additional data are required to verify dopamine stabilizer effects on UHDRS TMS. Trial sequential analysis confirmed the reliability of VMAT2 for TMC; however, the sample size was insufficient to draw conclusions about the effects of dopamine stabilizers on UHDRS TMS or their safety outcomes, indicating that additional data are needed. Conclusions: VMAT-2 inhibitors may suggest potential improvements in motor symptoms in Huntington\u2019s disease, while current evidence does not demonstrate a significant benefit of dopamine stabilizers. The safety profiles of both treatments appear generally comparable to placebo. Further rigorous and long-term studies are required to better establish their efficacy and safety.<\/jats:p>","DOI":"10.3390\/medsci13030201","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T08:37:39Z","timestamp":1758530259000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Safety of VMAT-2 Inhibitors and Dopamine Stabilizers for Huntington\u2019s Chorea: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1419-3885","authenticated-orcid":false,"given":"Lautaro Manuel","family":"Floridia Rietmann","sequence":"first","affiliation":[{"name":"Facultad de Ciencias M\u00e9dicas, Universidad Nacional del Litoral, Santa Fe 3000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7858-7724","authenticated-orcid":false,"given":"Candela","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma Alejandra","family":"Beltr\u00e1n Covarrubias","sequence":"additional","affiliation":[{"name":"Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3218-2359","authenticated-orcid":false,"given":"Jose Antonio","family":"Gomez Miranda","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad del del Salvador, San Salvador 1101, El Salvador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9330-3359","authenticated-orcid":false,"given":"Omar Enrique","family":"Brice\u00f1o Carde\u00f1a","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma de Yucat\u00e1n, M\u00e9rida 97000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0296-4981","authenticated-orcid":false,"given":"Shwetha","family":"Shenod","sequence":"additional","affiliation":[{"name":"PSG Institute of Medical Sciences & Research, Coimbatore 641004, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9255-577X","authenticated-orcid":false,"given":"Ada Victoria","family":"Marrero Peralta","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad Tecnol\u00f3gica de Santiago, Santiago de los Caballeros 51000, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4227-3107","authenticated-orcid":false,"given":"Genesis Mariana","family":"Ferrer Zavala","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, La Universidad del Zulia, Maracaibo 4002, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanth","family":"Hanumanthu","sequence":"additional","affiliation":[{"name":"International Faculty of Medicine, Tbilisi State Medical University, Tbilisi 0186, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Borges Sosa","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-9536","authenticated-orcid":false,"given":"Ernesto","family":"Calderon Martinez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas at Houston Medical Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"710","DOI":"10.3389\/fneur.2019.00710","article-title":"international guidelines for the treatment of Huntington\u2019s disease","volume":"10","author":"Ferreira","year":"2019","journal-title":"Front. 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