Tiapride Shows Fewer Safety–Related Discontinuations Than Tetrabenazine for Huntington Disease Chorea, Real-World Analysis Suggests

In a 25-year retrospective cohort study recently published in Clinical Therapeutics, researchers reported that tiapride was prescribed more frequently than tetrabenazine as first-line treatment for chorea in Huntington disease (HD) and was associated with significantly fewer adverse effect (AE)–related discontinuations.¹ The findings offer clinicians one of the longest real-world comparative analyses available for these 2 agents in the DACH region of Europe (Germany, Austria, and Switzerland), where both have regulatory approval for HD-associated chorea.

To date, there is no disease-modifying therapy that currently exists for HD, and symptomatic management of chorea remains a cornerstone of care. With deutetrabenazine (Austedo; Teva Pharmaceuticals) and valbenazine (Ingrezza; Neurocrine Biosciences) both approved in the United States and not yet approved in Europe, European neurologists may rely on tiapride and tetrabenazine for HD treatment, yet head-to-head real-world tolerability data with these agents have been scarce.¹

Study Overview

Senior author Beatrice Heim, MD, PhD, neurologist at Innsbruck Medical University in Austria, and colleagues conducted a single-center retrospective review of medical records from 140 adults with genetically confirmed HD seen at the Innsbruck outpatient clinic and trial center between January 2000 and April 2025. Of those, 62 patients received tiapride, tetrabenazine, or both at least once and formed the analytical cohort.

The study examined prescription patterns, tolerability, reasons for discontinuation, outcomes of reinitiation, and safety of combination therapy. Primary outcomes were analyzed at the treatment-course level; patients could contribute more than one course if treatment was stopped and later reinitiated. The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) and Total Functional Capacity (TFC) nearest to treatment initiation were extracted for exploratory comparisons.

Key Findings

Tiapride was prescribed as first-line therapy in 69% of cases versus 31% for tetrabenazine (P = .003). The preference for tiapride was statistically significant among women (P = .003) and in patients with higher disease burden as indexed by a CAG–Age Product score of at least 500 (P = .003).

Tolerability data revealed a clinically meaningful difference. Across all treatment courses, AE–related discontinuation occurred in 27% of tiapride courses compared with 55% of tetrabenazine courses (P = .003). An additional 6 courses of each drug required dose reduction rather than full discontinuation. The AE profiles were distinct: fatigue/apathy and Parkinsonism were the leading reasons for tiapride discontinuation or dose reduction, whereas depression, Parkinsonism, fatigue/apathy, and tardive syndromes including akathisia drove changes in tetrabenazine-treated patients. Notably, all 13 tetrabenazine discontinuations because of depression occurred exclusively in that group, not a single tiapride course was stopped for this reason.

READ MORE: Huntington Agent SKY-0515 Shows Favorable Trends Across cUHDRS Subcomponents in 12-Month Findings

For the 22 confirmed combination therapy periods identified, AE leading to discontinuation were concentrated in the first year (median combination duration for discontinued courses: approximately 6.4 months versus 14.5 months for ongoing combinations; P = .046). Reinitiation was attempted in 9 tiapride and 8 tetrabenazine courses, with most restarts remaining active at data cutoff, suggesting that tolerability profiles may evolve with disease progression.

Clinical Context

According to research, HD affects approximately 5.70 per 100,000 individuals in North America, Europe, and Australia.² The disease is uniformly progressive, with no approved disease-modifying therapy, placing the burden of management squarely on symptomatic interventions.¹ Current German Neurological Society guidelines acknowledge both tiapride and tetrabenazine as treatment options for HD chorea, whereas international guidelines recommend particular caution with tetrabenazine in patients with a history of depression.^3,4 The landmark randomized controlled trial establishing tetrabenazine's antichoreic efficacy was published in 2006, but prospective comparative data against tiapride remain absent.⁵

Interpretation

These findings should be interpreted with caution. The authors themselves emphasized that the apparent difference in tolerability is likely influenced by indication-related selection bias. Tetrabenazine-treated patients showed numerically, though not statistically significantly, higher motor burden and lower functional capacity at treatment initiation, suggesting the drug may have been channeled toward more advanced cases. The lower discontinuation rate with tiapride does not establish superior tolerability in the pharmacologic sense.

Limitations

The retrospective single-center design, 25-year observation window, and consequent heterogeneity in documentation quality were noted as significant constraints. Early records frequently lacked standardized motor or psychiatric scales, precise dosing information at the time of adverse events, and consistent follow-up intervals. The small subgroup sizes precluded regression-based predictor analyses. Polypharmacy, which was common in this cohort, could not be adequately controlled for retrospectively. Generalizability beyond a tertiary academic center in the DACH region is uncertain.

Future Research

Prospective comparative trials with standardized patient-reported outcomes, structured psychiatric monitoring, and systematic chorea severity ratings may be needed to confirm these findings and provide actionable guidance for long-term treatment selection. The authors also noted that reinitiation merits formal study given the observed feasibility in selected patients.

REFERENCES
1. Schwarzová K, Labrecque S, Hemicker G, et al. Long-Term Use of Tiapride and Tetrabenazine in Huntington's Disease: A 25-Year Retrospective Single-Center Analysis. Clin Ther. Published online May 29, 2026. doi:10.1016/j.clinthera.2026.05.005
2. Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington's disease: a systematic review and meta-analysis. Mov Disord. 2012;27(9):1083-1091. doi:10.1002/mds.25075
3. Saft C, Burgunder JM, Dose M, et al. Symptomatic treatment options for Huntington's disease (guidelines of the German Neurological Society). Neurol Res Pract. 2023;5(1):61. Published 2023 Nov 16. doi:10.1186/s42466-023-00285-1
4. Bachoud-Lévi AC, Ferreira J, Massart R, et al. International Guidelines for the Treatment of Huntington's Disease. Front Neurol. 2019;10:710. Published 2019 Jul 3. doi:10.3389/fneur.2019.00710
5. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366-372. doi:10.1212/01.wnl.0000198586.85250.13