Parkinsonism & related disorders · 2026
Safety and efficacy of VMAT2 inhibitors in Huntington Disease: A systematic review.
Систематический обзорСтатьяНазвание и аннотация: Перевод в очереди
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Baghaei Ava, Dehnavi Ali Zare, Hashempour Zahra, Bordelon Yvette, Jimenez-Shahed Joohi, Stimming Erin Furr, Koch Jessa, Dashtipour Khashayar
Аннотация
BACKGROUND: Chorea affects quality of life and functional independence in most adults with Huntington disease (HD). Vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine, deutetrabenazine, and valbenazine, are pharmacological agents used to manage HD-related chorea. This systematic review evaluates the safety and efficacy of these agents in individuals with HD.
METHODS: This review was conducted in accordance with PRISMA guidelines and registered with PROSPERO, CRD42024581306. A comprehensive literature search was performed for studies published up to July 3, 2025. Eligible studies included randomized controlled trials, cohort studies, and case-control studies. Two reviewers independently performed data extraction and risk-of-bias assessment.
RESULTS: Three randomized trials met eligibility criteria and were included in the final analysis. All three VMAT2 inhibitors significantly reduced Unified Huntington Disease Rating Scale Total Maximal Chorea scores. Clinical Global Impression-Improvement Scale for tetrabenazine and both Patient Global Impression of Change and Clinician Global Impression of Change ratings for deutetrabenazine and valbenazine favored active treatment. Deutetrabenazine modestly improved 36-Item Short Form Health Survey physical functioning and Swallowing Disturbance Questionnaire scores. Tetrabenazine was associated with higher adverse event (AE) rates; whereas valbenazine and deutetrabenazine demonstrated better tolerability.
DISCUSSION: This systematic review shows VMAT2 inhibitors significantly reduce chorea severity in HD. While tetrabenazine showed the greatest reduction in chorea scores, valbenazine and deutetrabenazine provided broader benefits on functional outcomes and improvement scales. Tetrabenazine had the highest rate of AEs, whereas deutetrabenazine demonstrated favorable tolerability, with fewer complications. Valbenazine demonstrated an intermediate safety profile. These differences should guide individualized treatment decisions in clinical practice.
METHODS: This review was conducted in accordance with PRISMA guidelines and registered with PROSPERO, CRD42024581306. A comprehensive literature search was performed for studies published up to July 3, 2025. Eligible studies included randomized controlled trials, cohort studies, and case-control studies. Two reviewers independently performed data extraction and risk-of-bias assessment.
RESULTS: Three randomized trials met eligibility criteria and were included in the final analysis. All three VMAT2 inhibitors significantly reduced Unified Huntington Disease Rating Scale Total Maximal Chorea scores. Clinical Global Impression-Improvement Scale for tetrabenazine and both Patient Global Impression of Change and Clinician Global Impression of Change ratings for deutetrabenazine and valbenazine favored active treatment. Deutetrabenazine modestly improved 36-Item Short Form Health Survey physical functioning and Swallowing Disturbance Questionnaire scores. Tetrabenazine was associated with higher adverse event (AE) rates; whereas valbenazine and deutetrabenazine demonstrated better tolerability.
DISCUSSION: This systematic review shows VMAT2 inhibitors significantly reduce chorea severity in HD. While tetrabenazine showed the greatest reduction in chorea scores, valbenazine and deutetrabenazine provided broader benefits on functional outcomes and improvement scales. Tetrabenazine had the highest rate of AEs, whereas deutetrabenazine demonstrated favorable tolerability, with fewer complications. Valbenazine demonstrated an intermediate safety profile. These differences should guide individualized treatment decisions in clinical practice.