Antipsychotics improve functional capacity, independence in HD
Drugs differ in effectiveness for specific symptoms, clinical trial data show
Certain antipsychotic medications, including the Huntington’s approved therapy tetrabenazine (sold as Xenazine in the U.S., with generics available), significantly improve functional capacity in people with Huntington’s disease.
That’s according to data from a one-year, Phase 3 clinical trial in France called NEUROHD (NCT00632645), which compared the benefits and adverse events of tetrabenazine, tiapride, and olanzapine.
Results also showed that some medications were more effective than others at treating specific symptoms and were linked to distinct adverse events. Tetrabenazine’s beneficial effects on chorea (irregular and uncontrolled movements) were confirmed. Olanzapine was shown to lessen chorea, irritability, and overall behavioral symptoms, while tiapride was found to reduce irritability.
“These results underscore the importance of symptom-specific, individualized treatment,” the researchers wrote.
The study, “Comparison of tetrabenazine, tiapride and olanzapine in Huntington’s disease: a one-year French randomized multicenter study (Neuro-HD),” was published in Parkinsonism & Related Disorders.
Treating a range of Huntington’s symptoms
Huntington’s is a genetic neurodegenerative disorder marked by a wide range of symptoms, including motor issues, cognitive deficits, and behavioral problems such as irritability, agitation, anxiety, and depression.
Antipsychotics, also called neuroleptics, are medications originally developed for psychosis — seeing or hearing things that aren’t real (hallucinations) and/or having fixed beliefs with no basis in reality (delusions).
These therapies are thought to work mainly by modulating the activity of dopamine, a brain signaling molecule, though their exact mechanism of action is not fully understood.
Antipsychotics — including tetrabenazine, tiapride (sold outside the U.S. as Tiapridal and other brand names, with generics available), and olanzapine (sold as Zyprexa, with generics available) — are commonly used in Huntington’s to manage both chorea and irritability.
“However, their use is primarily supported by case studies or small-scale … trials, rather than [appropriately controlled] studies providing high-level evidence,” the researchers wrote.
The exception is tetrabenazine, an approved therapy for Huntington’s-related chorea, which has been shown to be superior to a placebo at easing chorea in an appropriately controlled clinical trial. Tiapride has been approved for treating chorea in France since the 1980s, before appropriately controlled trials became mandatory for regulatory approvals.
“None of these treatments has been specifically evaluated for the psychiatric symptoms of HD [Huntington’s disease],” the researchers wrote, adding that there’s minimal data comparing the benefits and risks of different antipsychotic meds in Huntington’s patients.
NEUROHD recruited 179 adults with Huntington’s and an indication for neuroleptic treatment from 11 French centers. Participants were randomly assigned to receive either tetrabenazine, tiapride, or olanzapine for a year.
“These treatments were selected based on their frequency of use in France (with olanzapine being the most prescribed), their marketing authorization status ([tetrabenazine] and tiapride), and prior evidence for their efficacy,” the researchers wrote.
The study’s main goal was to evaluate changes in the Independence Scale, a measure of patients’ ability to function independently in daily life. Secondary goals included changes in specific symptom measures.
Independence Scale scores showed a similar, significant reduction, reflecting better functional capacity, across all treatment groups after one year. Tetrabenazine and olanzapine were associated with faster benefits, detected as early as six months.
Further analyses showed some differences in specific symptoms. For example, tetrabenazine and olanzapine led to a significant reduction in chorea scores, whereas tiapride did not.
Olanzapine and tiapride were both shown to significantly ease irritability, with olanzapine having a significantly stronger effect than the other two medications. Olanzapine was also superior to the other therapies at reducing total behavioral score, reflecting less severe behavioral problems.
Safety data differed among the three medications: Mood disorders, drowsiness, fatigue, and sedation were more common with tetrabenazine than with either of the other two medications; tiapride was associated with worse eye-related motor symptoms, and olanzapine with increased rigidity.
Participants given olanzapine appeared less likely to discontinue treatment than those on the other two medicines, which suggests that olanzapine may have a “more favorable efficacy/risk profile” than tetrabenazine or tiapride, the researchers wrote.
The scientists said the findings could help Huntington’s patients and clinicians make decisions about which antipsychotics to try, based on each individual’s situation.
“Overall, while all three treatments demonstrated some efficacy, our findings offer evidence-based guidance to support individualized treatment decisions based on each patient’s clinical profile,” they concluded.
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