Comparison of tetrabenazine, tiapride and olanzapine in Huntington's disease: a one-year French randomized multicenter study (Neuro-HD)

Abstract

Introduction: Chorea and behavioral symptoms in Huntington's disease (HD) have been treated with neuroleptics and related drugs for over 50 years, yet direct randomized comparisons are scarce. This study assessed the efficacy and safety of olanzapine, tetrabenazine, and tiapride in HD, with the Independence Scale as the primary outcome and components of the Unified Huntington's Disease Rating Scale as secondary outcomes. Methods: We conducted a pragmatic, randomized, open-label trial across 11 centers of the French-Speaking Huntington's Network, enrolling 179 patients with Huntington's disease. Participants were randomized into three treatment arms—olanzapine, tiapride, or tetrabenazine—and followed for 52 weeks. Results: Independence Scale declined similarly across all treatment arms from baseline to week 52. Chorea improved significantly with both tetrabenazine and olanzapine, whereas rigidity increased only with olanzapine. Irritability improved with olanzapine and tiapride, and the total behavioral score improved only with olanzapine. Tetrabenazine was most frequently associated with mood disorders and sedation, while olanzapine caused occasional weight gain and mild increases in LDL and total cholesterol. Discontinuation rates were lowest with olanzapine, with significantly fewer withdrawals due to depression or suicidal ideation. Conclusion: Olanzapine improved chorea, behavior, and irritability, although with a slight increase in rigidity. Tetrabenazine confirmed efficacy for chorea but was associated with mood disorders and drowsiness, while tiapride reduced irritability. These results underscore the importance of symptom-specific, individualized treatment.