Antidopaminergics linked to worse cognitive, functional outcomes in HD at 6 years

Key takeaways:

• Researchers analyzed Huntington’s progression for up to 6 years in those on antidopaminergic medication.
• ADMs were linked to faster disease progression and worsening bradykinesia.

Antidopaminergic medications were linked to worsening cognitive and functional effects that accelerate disease progression in Huntington’s disease, according to research presented at the Congress of the European Academy of Neurology.

“Antidopaminergic medications, comprised of anti- chorea medications (VMAT2 inhibitors [VMAT2i]) and neuroleptics, are used for the symptomatic treatment of [Huntington’s disease],” Jeffrey Long, PhD, a professor of psychiatry and biostatistics at the University of Iowa, and colleagues wrote. “No prospective, double- blind studies have assessed the long term effects of [antidopaminergics] on disease progression in HD.”

Long and colleagues sought to assess long-term effects of prescribing antidopaminergics (ADMs) on disease progression in HD.

Their study measured rates of progression for up to 6 years in an early manifest population (Total Functional Capacity [TFC] score at least 7; Diagnostic Confidence Level = 4) from the ENROLL- HD clinical research platform and prospective observational study, using the inclusion criteria of the PROOF- HD study, a phase 3, randomized, double-blind placebo-controlled endeavor to evaluate safety and efficacy of pridopidine in early-stage HD.

Each of four comparisons involved matching groups of individuals on and off the particular medication of interest: ADMs (n = 853 per group), neuroleptics (n = 495 per group), VMAT2i (n = 198 per group), antidepressants (n = 331 per group). Pairs were matched at baseline using a propensity score constructed with 12 covariates including the Symbol Digit Modalities Test (SDMT), Stroop word test (SWR) and the composite Unified Huntington Disease Rating Scale (cUHDRS).

According to results, participants on ADMs had faster disease progression across multiple measures including TFC, SDMT, SWR and cUHDRS. Long and colleagues observed similar results when analyzing neuroleptics and VMAT2i alone. On cUHDRS-Total Motor Score subscales, ADM use was associated with improvement of chorea, as well as with worsening of bradykinesia.

Data further showed that participants on antidepressants showed no difference in disease progression rate.

“Additional analyses will assess the impact of specific ADM medications/doses to identify treatments with minimal impact on disease progression,” Long and colleagues wrote.