2024 American Academy of Neurology Abstract Website

Objective:

To evaluate the association between common concomitant medication use and global clinical progression in early manifest Huntington Disease (HD).

Background:

To date, no double-blind clinical trial has assessed the long-term effect of antidopaminergic medications (ADMs) (neuroleptics and VMAT2 inhibitors) on disease progression in HD. Observational studies suggest that these ADMs may adversely affect the rate of HD decline (Harris et al. 2020; Huntington Study Group 2006; and Tedroff et al. 2015).

Design/Methods:

Rates of progression up to six years were assessed in an early manifest population (TFC >7) from the Enroll-HD database that were either exposed to ADMs or antidepressants at all visits (treatment) or not exposed at any visit (control). Four groups (ADMs n=1706, neuroleptics n=930, VMAT2 inhibitors n=396, and antidepressants n=662) were propensity score matched to their respective control at study entry across 12 covariates.

Results:

Participants on ADMs had significantly faster disease progression compared to the control group off ADMs, across multiple measures including total functional capacity (TFC) (p<0.001), symbol digit modalities test (SDMT) (p<0.001), Stroop Word test (SWR) (p<0.001), and the composite UHDRS (cUHDRS) (p<0.001). However, there was no difference in participants using ADMs in progression on total motor score (TMS). Similar results were observed with a 3-year duration, and when assessing the effect of neuroleptics and VMAT2 inhibitors alone, VMAT2 had a larger effect. On TMS subscales, ADM use was associated with improvement on the chorea subscale, however it was also associated with faster progression on bradykinesia (p=0.001) and gate-balance (p<0.001) subscales. Participants on antidepressants showed no difference in progression rate across all outcome measures evaluated.

Conclusions:

ADM use was associated with accelerated HD progression across multiple measures in this analysis. These results should be considered in the design, conduct and analysis of clinical trials in HD.