Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr;12(4):418-431.
doi: 10.1002/mdc3.14343. Epub 2025 Jan 31.

Pharmacological Treatment of Neuropsychiatric Symptoms in Huntington's Disease: A Systematic Review

Ruben L Andriessen  1   2 , Mayke Oosterloo  1   2 , Jory Molema  1 , Maud M J Daemen  2   3 , David E J Linden  1   2   3 , Albert F G Leentjens  2   3
Affiliations

Pharmacological Treatment of Neuropsychiatric Symptoms in Huntington's Disease: A Systematic Review

Ruben L Andriessen et al. Mov Disord Clin Pract. 2025 Apr.

Abstract

Background: Studies focusing on the treatment of neuropsychiatric symptoms (NPS) in Huntington's disease (HD) are scarce and show a wide variation in design, outcome measures and methodological quality. The effectiveness of pharmacological treatment of NPS in HD has not been systematically reviewed so far.

Objective: To provide an overview of the available literature on the effectiveness of pharmacological treatment of NPS in HD.

Methods: PubMed and the Cochrane library were systematically searched for studies assessing the effects of pharmacotherapy of NPS, both as a primary and as secondary outcome. A risk of bias assessment was performed for each article.

Results: Fifteen articles qualified for critical evaluation: 10 randomized controlled trials (RCTs) (five placebo-controlled and five cross-over) and five open label studies. One RCT reported improvement of the overall NPS with nabilone treatment; another RCT reported that fluoxetine slightly improved irritability. Lower-level evidence from open studies suggests that the atypical antipsychotics cariprazine, olanzapine and risperidone may improve overall NPS, and that cariprazine, venlafaxine XR and olanzapine may improve depression. In addition, olanzapine may improve obsessive thoughts, aggression, anxiety and irritability.

Conclusions: We conclude that although NPS in HD are common, hardly any clinical trials have addressed their treatment. As a result, convincing evidence that could guide clinical practice is lacking. More focused, and larger, multicenter trials focusing on NPS are urgently needed to generate the knowledge necessary to support the development of evidence-based clinical treatment guidelines.

Keywords: Huntington's disease; neuropsychiatric symptoms; psychotropic medication; systematic review; treatment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
PRISMA flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐Analyses.
See this image and copyright information in PMC

References

    1. Roos RA. Huntington's disease: a clinical review. Orphanet J Rare Dis 2010;5:40. - PMC - PubMed
    1. Group THsDCR . A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's disease collaborative research group. Cell 1993;72(6):971–983. - PubMed
    1. Consortium GMoHsDG‐H . CAG repeat not polyglutamine length determines timing of Huntington's disease onset. Cell 2019;178(4):887–900.e14. - PMC - PubMed
    1. Rawlins MD, Wexler NS, Wexler AR, Tabrizi SJ, Douglas I, Evans SJ, Smeeth L. The prevalence of Huntington's disease. Neuroepidemiology 2016;46(2):144–153. - PubMed
    1. Evans SJ, Douglas I, Rawlins MD, Wexler NS, Tabrizi SJ, Smeeth L. Prevalence of adult Huntington's disease in the UK based on diagnoses recorded in general practice records. J Neurol Neurosurg Psychiatry 2013;84(10):1156–1160. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources