Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD)

Abstract

ObjectivesAlterations in dopamine neurotransmission underlie some of the clinical features of Huntington’s disease (HD) and as such are a target for therapeutic intervention, especially for the treatment of chorea and some behavioural problems. However, justification for such an intervention is mainly based on case reports and small open label studies and the effects these drugs have on cognition in HD remain unclear.MethodsIn this study, we used the Enroll-HD observational database to assess the effects of antidopaminergic medication on motor, psychiatric and cognitive decline, over a 3-year period. We first looked at the annual rate of decline of a group of HD patients taking antidopaminergic medication (n=466) compared with an untreated matched group (n=466). The groups were matched on specified clinical variables using propensity score matching. Next, we studied a separate group of HD patients who were prescribed such medications part way through the study (n=90) and compared their rate of change before and after the drugs were introduced and compared this to a matched control group.ResultsWe found that HD patients taking antidopaminergic medication had a slower progression in chorea and irritability compared with those not taking such medications. However, this same group of patients also displayed significantly greater rate of decline in a range of cognitive tasks.ConclusionIn conclusion we found that antidopaminergic treatment is associated with improvements in the choreic movements and irritability of HD but worsens cognition. However, further research is required to prospectively investigate this and whether these are causally linked, ideally in a double-blind placebo-controlled trial.

An MDS Evidence‐Based Review on Treatments for Huntington's Disease

“…For instance, observational evidence suggests that although antidopaminergic medication is associated with an improvement in chorea and irritability, it may also aggravate cognition. 70,71 Overall, the usefulness of such an evidence-based medicine review such as the current one in day-to-day clinical practice requires the integration of the highest level of evidence from clinical studies with various factors considered before deciding on the best treatment plan for the individual patient. These factors include the local availability of the drug/intervention, local drug approval, physicians' individual clinical experience and judgment, economic influences, and other patient-/medical-related factors such as side effects and tolerability, comorbidities, and comedications as well as patient preferences.…”

“…For the great majority of interventions used in clinical practice, decisions concerning the risk of parkinsonism, somnolence, and apathy are based on observational studies or extrapolated from other indications. For instance, observational evidence suggests that although antidopaminergic medication is associated with an improvement in chorea and irritability, it may also aggravate cognition 70,71 …”

Metacognitive insight into cognitive performance in pre and early-stage Huntington’s disease

“…We did not include medication effects in our analyses. Dopamine is well-known to affect cognition (33) and manifest HD patients are often prescribed dopamine antagonists to help with the disease features, but these can increase the rate of cognitive decline (34). However, only 4 of 29 (13.8%) gene-carriers in this study were taking anti-dopaminergic medication, and all at low dose, so the pattern of findings cannot be explained by this.…”

Therapeutic Potential of Astrocyte Transplantation

“…Similar to other neurodegenerative proteinopathies discussed above, the pathological hallmark of HD is the aggregation of the mutant huntingtin protein (mtHtt), which can trigger the progressive neurodegeneration, particularly of the striatal GABAergic medium spiny neurons (MSNs), although other areas such as cortex also become affected 227 . No cure exists except palliative treatments that aim to alleviate the involuntary movements, or chorea, by reducing dopaminergic neurotransmission, and to suppress psychiatric manifestations 228 , 229 .…”