Antidopaminergic Medications and Clinical Outcomes in Huntington Disease: Evidence From the PROOF-HD Placebo-Controlled Trial.
Karen E Anderson, Andrew M Tan, Andrew Feigin et al.
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In 30 seconds
This post hoc analysis of the placebo arm of the randomized PROOF-HD trial examined associations between antidopaminergic medication (ADM) use and clinical outcomes in adults with Huntington disease. Among 247 participants, 135 used ADMs during the study period. ADM use was associated with faster decline across several global, functional, cognitive, and motor measures. At week 52, mean-change differences favored participants off ADMs by 0.66 points on cUHDRS (95% CI 0.31-1.01; p = 0.0002) and 0.85 points on TFC (95% CI 0.47-1.22; p < 0.0001).
Key findings
- At week 52, cUHDRS mean change favored participants off ADMs by 0.66 points (95% CI 0.31-1.01; p = 0.0002).
- At week 52, TFC mean change favored participants off ADMs by 0.85 points (95% CI 0.47-1.22; p < 0.0001).
- From week 39 onward, findings for SDMT, SWR, and TMS were significant or directionally consistent with greater decline among ADM users.
- Antipsychotic-only, VMAT2 inhibitor-only, and higher-dose ADM use were each associated with greater cUHDRS and TFC decline than no ADM use.
Why it matters
ADM exposure may influence measured disease trajectories in Huntington disease, including outcomes used in clinical trials. Considering medication use, class, and dose when interpreting these measures may help distinguish treatment-related differences from underlying disease progression. The findings also highlight the need to account for potential confounding when comparing outcomes among patients taking and not taking these medications.
What to keep in mind
This was a post hoc analysis of the trial’s placebo arm, and residual confounding by disease severity cannot be excluded; medication exposure was not randomized.