Antidopaminergic Meds Ease Chorea But May Worsen Cognition, Study Finds

Antidopaminergic medications are associated with lesser chorea and irritability in people with Huntington’s disease, but they may worsen their cognitive skills, data from the largest observational study of the disease show.

Future, prospective studies are needed to confirm these findings, and to determine whether treatments to lower dopamine levels indeed contribute to cognitive decline in this patient population, the researchers noted.

The study, “Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD),” was published in the Journal of Neurology, Neurosurgery & Psychiatry.

Huntington’s patients frequently experience chorea — brief and abrupt involuntary movements — that is associated with higher-than-normal levels of dopamine, a key signaling molecule in the brain.

In addition to its role in motor function, dopamine affects several cognitive and psychiatric processes. Both excessive and deficient levels of this signaling molecule can impair a person’s cognitive abilities.

Antidopaminergic treatments, or those working to reduce dopamine levels, are used to treat chorea and some behavioral problems in Huntington’s patients. However, such treatments can push dopamine levels so far down that other dopamine-dependent brain functions, such as cognition, might decline.

“It is thus possible that antidopaminergic treatment targeted at the motor impairments of HD also has an impact on non-motor features of the disease,” the researchers wrote.

A team of researchers at the University of Cambridge evaluated the effects of antidopaminergic medications on the motor, cognitive, and psychiatric health of people with Huntington’s disease over a three-year period.

They analyzed data from the world’s largest observational study of Huntington’s — called Enroll‐HD — which at the time involved more than 15,000 people with a genetic diagnosis of the disease and who undergo a battery of motor, cognitive, and psychiatric assessments once a year. (Currently, more than 19,800 patients are listed as “active” study participants.)

Motor function, including chorea, is evaluated using the Unified Huntington’s Disease Rating Scale, psychiatric features through the problems behavioral assessment, and cognitive function with the symbol digit modalities test, phonemic verbal fluency, the stroop task, and the trail making test.

The team first analyzed two groups of adult patients with manifest disease who had completed at least two annual assessments, matched on specific clinical variables. One group included 466 patients being treated with antidopaminergic medication, and the other included 466 patients who were not (used as controls).

Patients were an average age of 54, had been living with a Huntington’s diagnosis for an average of three years, and had completed a mean of three annual assessments during Enroll-HD. Xenazine (tetrabenazine) was the most common antidopaminergic medication used.

At the study’s beginning, people in the antidopaminergic group appeared to be at a similar disease stage, but had significantly greater motor, psychiatric, and cognitive impairments than those in the control group.

Greater motor and behavioral impairments may be expected in a patient population prescribed antidopaminergic medication to treat these symptoms, the researchers noted.

Results showed that patients on antidopaminergic medication had a significantly slower annual progression in chorea and irritability, with no changes in depression and apathy compared with controls. However, such treatment was also associated with a significantly greater rate of decline in nearly all cognitive tasks.

Similar findings were observed when looking at the rate of functional changes before and after treatment in a group of 90 patients with four completed assessments, who started antidopaminergic medication halfway through the study.

After beginning treatment, these patients showed a significant drop in chorea and irritability, but worsening cognition. These differences were also detected when comparing with data from 108 matched controls.

Notably, initiation of antidopaminergic medication was also associated, for the first time, with a significant improvement in rapid eye movements known as saccade that affect Huntington’s patients. Further research is needed to confirm this potential link.

These findings suggest that while antidopaminergic treatment may lower chorea and irritability in Huntington’s patients, it may also worsen their cognitive abilities, “which has important clinical implications since patients often report cognitive impairments to be more disruptive to daily life than motor disturbances,” the researchers wrote.

They noted that future prospective studies using tasks specific to dopamine-related functions are needed to fully understand whether antidopaminergic medication is directly causing cognitive difficulties in these patients.