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The effectiveness of pharmacological treatment of NPS in HD has not been systematically reviewed so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To provide an overview of the available literature on the effectiveness of pharmacological treatment of NPS in HD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen articles qualified for critical evaluation: 10 randomized controlled trials (RCTs) (five placebo\u2010controlled and five cross\u2010over) 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\u2010level 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2010based clinical treatment guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.14343","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T02:18:48Z","timestamp":1738376328000},"page":"418-431","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacological Treatment of Neuropsychiatric Symptoms in Huntington's Disease: A Systematic Review"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6337-0952","authenticated-orcid":false,"given":"Ruben L.","family":"Andriessen","sequence":"first","affiliation":[{"name":"Department of Neurology Maastricht University Medical Center  Maastricht The Netherlands"},{"name":"Mental Health and Neuroscience Research Institute Maastricht University  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