{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:13:51Z","timestamp":1793708031867,"version":"4.6.1"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Levodopa-induced dyskinesia (LID) remains one of the most disabling complications of long-term dopaminergic therapy in Parkinson\u2019s disease. Despite decades of investigation, only amantadine has been established as the standard FDA-approved treatment, while istradefylline provides a complementary non-dopaminergic option. Most other candidate agents\u2013including memantine, clozapine, and serotonergic or noradrenergic modulators\u2013have shown inconsistent efficacy or safety limitations, underscoring persistent translational challenges between preclinical promise and clinical outcomes. In addition to pharmacological therapies, deep brain stimulation (DBS) serves as an established non-pharmacological intervention for advanced cases. This review systematically synthesizes current pharmacological strategies, consolidating evidence on mechanisms, efficacy, safety, and regulatory status. We further highlight failed or inconclusive trials, emphasize gaps in trial design and patient heterogeneity, and discuss emerging approaches such as individualized therapeutic frameworks, novel drug delivery systems, and AI-assisted drug discovery. Potential complementary pathways, including Traditional Chinese Medicine (TCM), are also briefly noted as alternative directions. By linking mechanistic insights with therapeutic evidence, this review provides an updated framework for optimizing LID management and guiding future research directions.<\/jats:p>","DOI":"10.3389\/fnagi.2025.1684885","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T05:36:55Z","timestamp":1761025015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Levodopa-induced dyskinesia in Parkinson\u2019s disease: an updated review of pharmacological treatments"],"prefix":"10.3389","volume":"17","author":[{"given":"Feifei","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1080\/17582024.2025.2528557","article-title":"Recent and on-going trials for the treatment of levodopa-induced dyskinesia: A review of the clinical trial databases.","volume":"15","author":"Al-Kassmy","year":"2025","journal-title":"Neurodegener. 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