Objective: To compare the efficacy of risperidone and olanzapine to tetrabenazine (TBZ) for the management of Huntington’s chorea in Enroll-HD participants.

Background: TBZ is provenly-effective and FDA-approved for the treatment of chorea in Huntington’s disease (HD). Antipsychotic drugs (APD), such as Risperdal and Olanzapine, are often prescribed off-label for HD chorea, especially when psychiatric comorbidities are present. The APD’ anti-choreic efficacy is presumed primarily from their long-standing use by HD experts, as they have never been evaluated in large clinical trials.

Methods: This was a retrospective analysis using the database from Enroll-HD, a longitudinal, observational study with 8714 participants. Those with manifest HD were grouped based on their use of risperidone, olanzapine, or TBZ. The effects of these anti-choreic drugs were compared using MANCOVA analyses. The primary outcome measure was the total motor score (TMS) annual rate of change between the baseline and second visits. Secondary outcome measures included TMS changes and the rates of change between the baseline and second visits of the: total chorea score, total functional capacity score, weight and body mass index (BMI). Covariates included sex, years between visits and baseline: TMS, TFC, and disease burden score. An exploratory outcome measure was the odds of having an annualized improvement in the TMS by at least 3.3 units, which was TBZ’s treatment effect in the TETRA-HD study.1

Results: The risperidone group showed an improvement in the annualized percent change in TMS of 3.9% compared to a 17.5% worsening in the TBZ group (p=0.042). In addition, the odds of having an annualized improvement in the TMS by at least 3.3 units was significantly higher in subjects taking risperidone (42.9%) vs those on TBZ (9.0%) (p=0.031). The olanzapine group increased in weight (p=0.023) and BMI (p=0.022) compared to the TBZ group. The APD and TBZ results were otherwise comparable.

Conclusions: This is the first study to provide robust, objective data on the anti-choreic effect of risperidone and olanzapine. It is also the first study to compare these APD to TBZ for their efficacy on HD chorea. Our results establish that risperidone and olanzapine are comparable to TBZ, but for some superiority to tetrabenazine on certain measures. These findings bridge the gap between expert opinion and evidence-based medicine in the management of HD chorea.

References: 1. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington Disease: A randomized controlled Trial. Neurology 2006;66:366-372.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparing-risperidone-and-olanzapine-to-tetrabenazine-for-the-management-of-huntingtons-chorea/