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Fluctuations emerge in eventually all people with Parkinson\u2019s disease, and may lead to a high burden of motor and non-motor disability and significantly impair participation if they are inadequately treated. In recent years, the range of therapeutic options has expanded considerably. While different types of oral dopaminergic substances are initially applied to control fluctuations, additional routes of administration now encompass sublingual, inhalative, subcutaneous and transdermal applications. Different choices exist for on-demand and continuous pump therapies, as well as for deep brain stimulation. In this narrative review, we summarize the state of the art in the identification and treatment of motor and non-motor fluctuations in Parkinson\u2019s disease. Moreover, we discuss practical aspects of managing fluctuations, address yet unresolved questions and we offer insights into upcoming clinical developments.<\/jats:p>","DOI":"10.1007\/s00702-025-02990-4","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T05:29:42Z","timestamp":1753680582000},"page":"309-324","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Motor and non-motor fluctuations in Parkinson\u2019s disease: the knowns and unknowns of current therapeutic approaches"],"prefix":"10.1007","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-7386","authenticated-orcid":false,"given":"Martin","family":"Regensburger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-6837","authenticated-orcid":false,"given":"Ilona","family":"Csoti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8574-3297","authenticated-orcid":false,"given":"Wolfgang H.","family":"Jost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-8866","authenticated-orcid":false,"given":"Zacharias","family":"Kohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-0821","authenticated-orcid":false,"given":"Stefan","family":"Lorenzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5403-1959","authenticated-orcid":false,"given":"David J.","family":"Pedrosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-7096","authenticated-orcid":false,"given":"Paul","family":"Lingor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"2990_CR1","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3233\/jpd-202224","volume":"11","author":"G Abbruzzese","year":"2020","unstructured":"Abbruzzese G, Kulisevsky J, Bergmans B et al (2020) A European observational study to evaluate the safety and the effectiveness of Safinamide in routine clinical practice: the SYNAPSES Trial1. 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He was consultant and \/ or speaker for Zambon GmbH, Ever Pharma GmbH, Abbvie GmbH and Bial GmbH, and he received travel compensation from Desitin. IC was consultant and \/ or speaker for Danone, Neuraxpharm, Zambon GmbH, Abbvie GmbH, Desitin and Bial GmbH, and she received travel compensation from Abbvie. WJ received consultancy fees or speaker honoraria from Abbvie GmbH, Bial GmbH, Desitin, Stada and Zambon GmbH. ZK was consultant and \/ or speaker for Bial GmbH and Stadapharm GmbH, and he received travel compensation from Desitin and Medtronic. SL has no competing interests to declare that are relevant to the content of this article. He has received honoraria vom Abbvie GmbH and travel from Bial GmbH. DP received honoraria as a speaker at symposia sponsored by AbbVie Inc., Bayer, Bial, Boston Scientific Corp., Esteve Pharmaceuticals, Medtronic and Zambon. He received consultancy fees from AbbVie Inc., Bial, Boston Scientific Corp., Bayer, and Desitin, and he was awarded a scientific grant from Boston Scientific Corp. for a project entitled \u201cSensor-based Optimization of Deep Brain Stimulation Settings in Parkinson\u2019s Disease\u201d (COMPARE-DBS: Computerized Parameter Optimization of Deep Brain Stimulation in Idiopathic Parkinson\u2019s Syndrome). Lastly, DJP had his travel expenses reimbursed by Bial, Desitin, Esteve Pharmaceuticals GmbH, and Boston Scientific Corp. for conference participation. PL reports grants from the Bundesministerium f\u00fcr Bildung und Forschung and the Deutsche Forschungsgemeinschaft; consulting fees from AbbVie, Amylyx, Bial, Desitin, ITF Pharma, Novartis, Stadapharm, Raya Therapeutic, Woolsey Pharmaceuticals, and Zambon; partially unrelated to the scope of the submitted work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}