J015 The effect of antidopaminergic medications on Huntington disease (HD) progression

<h3>Background</h3> Antidopaminergics (ADMs; VMAT2 inhibitors and neuroleptics [off-label]), are used for the symptomatic treatment of HD and are associated with faster rates of decline. To date, no prospective, double-blind studies have assessed the long-term effects of ADMs on HD progression, but observational data are available. <h3>Aims</h3> To assess the effect of ADMs on rates of progression in early HD (TMS ≥ 20, DCL = 4, TFC ≥ 7, IS ≤ 90) using the ENROLL-HD database. <h3>Methods</h3> Causal analysis was performed using a new-user design to account for use history. Participants were not on medication at the first visit, but the exposure group (N = 380) was on medication for the 2-year follow-up, whereas the unexposed group (N = 792) was always off. Target maximum likelihood estimation was used to estimate the mean difference of the groups at 2 years adjusting for 28 confounders. Outcomes were the main UHDRS variables, including the composite (cUHDRS), and motor subscales. 99% CIs were used for inference. <h3>Results</h3> Results show participants on ADMs had a significantly smaller mean compared to those off for TFC (99% CI = [-1.04, -.28]), SDMT [-2.90, -1.07], SWR [-4.80, -1.04], and cUHDRS [-.96,-.32]. The on-ADMs group had a significantly larger mean for the bradykinesia scale [.02, 1.72]. Other outcomes had CIs that covered 0 figure 1. <h3>Conclusion</h3> ADM use was associated with faster progression of functioning and cognitive performance. These observations have important implications for the conduct and interpretation of investigational studies of disease modifying agents in HD and for medical practice.