{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:41:41Z","timestamp":1772818901633,"version":"3.50.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI15C1240"],"award-info":[{"award-number":["HI15C1240"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI15C1240"],"award-info":[{"award-number":["HI15C1240"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Although Idiopathic Parkinson\u2019s disease (IPD) develops in considerable patients with drug-induced Parkinsonism (DIP), the association hasn\u2019t been well defined. We aimed to evaluate the underlying association and risk factors of DIP and IPD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective cohort study using National Health Insurance Claims data in 2011\u20132016 was conducted. New-onset DIP patients in 2012 were selected and matched with active controls having diabetes mellitus at a 1:4 ratio by age, sex, and Charlson\u2019s Comorbidity Index score. Comorbidity, causative drugs, and prescription days were evaluated as covariates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 441 DIP were selected. During the 4-year follow up, 14 IPD events in the DM group but 62 events in the DIP group were observed (adjusted hazard ratio, HR: 18.88, 95% CI, 9.09\u201339.22, adjusting for comorbidities and causative drugs). IPD diagnosis in DIP was observed high in males compared to females (15.58\/13.24%). The event was the most within the 1<jats:sup>st<\/jats:sup> year follow-up, mean days 453 (SD 413.36). Subgroup analysis in DIP showed calcium channel blocker (verapamil, diltiazem, and flunarizine) was significantly associated with increased IPD risk (HR: 2.24, 95% CI, 1.27\u20133.93).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Increased IPD in DIP patients might not be from the causal toxicity of antidopaminergic effects but from a trigger by the causative drugs on the DIP patients who already had subclinical IPD pathology. DIP can serve as a strong proxy for IPD incidence. Subjects who develop DIP should be monitored carefully for potential IPD incidence.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0247354","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T18:28:52Z","timestamp":1614623332000},"page":"e0247354","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":39,"title":["Drug-induced Parkinsonism: A strong predictor of idiopathic Parkinson\u2019s disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-4349","authenticated-orcid":true,"given":"Sohyun","family":"Jeong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyemin","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun Joong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeo-Il","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8771-8693","authenticated-orcid":true,"given":"Sunmee","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"issue":"2","key":"pone.0247354.ref001","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/mds.26839","article-title":"Incidence and time trends of drug-induced parkinsonism: A 30-year population-based study","volume":"32","author":"R Savica","year":"2017","journal-title":"Mov Disord"},{"key":"pone.0247354.ref002","article-title":"Time Trends in the Incidence of Parkinson Disease","author":"R Savica","year":"2016","journal-title":"JAMA Neurology"},{"issue":"3","key":"pone.0247354.ref003","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00213-010-2079-1","article-title":"Risk for antipsychotic-induced extrapyramidal symptoms: influence of family history and genetic susceptibility","volume":"214","author":"M Kasten","year":"2011","journal-title":"Psychopharmacology (Berl)"},{"key":"pone.0247354.ref004","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2165\/11598540-000000000-00000","article-title":"Drug-induced parkinsonism in the elderly: incidence, management and prevention","volume":"29","author":"J Lopez-Sendon","year":"2012","journal-title":"Drugs Aging"},{"key":"pone.0247354.ref005","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1212\/WNL.52.6.1214","article-title":"Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976\u20131990","volume":"52","author":"J Bower","year":"1999","journal-title":"Neurology"},{"key":"pone.0247354.ref006","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1159\/000102857","article-title":"Prolonged drug-induced Parkinsonism","volume":"35","author":"HJ Klawans","year":"1973","journal-title":"Confin Neurol"},{"key":"pone.0247354.ref007","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.parkreldis.2014.05.011","article-title":"Differentiating drug-induced parkinsonism from Parkinson\u2019s disease: an update on non-motor symptoms and investigations","volume":"20","author":"F Brigo","year":"2014","journal-title":"Parkinsonism Relat Disord"},{"issue":"6","key":"pone.0247354.ref008","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1136\/jnnp.51.6.850","article-title":"Neuroleptic-induced Parkinson\u2019s syndrome: clinical features and results of treatment with levodopa","volume":"51","author":"R Hardie","year":"1988","journal-title":"Journal of neurology, neurosurgery, and psychiatry"},{"key":"pone.0247354.ref009","article-title":"Drug-induced parkinsonism in the elderly","volume":"2","author":"P Stephen","year":"1984","journal-title":"Lancet"},{"issue":"1","key":"pone.0247354.ref010","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.archger.2012.05.001","article-title":"Combined use of (1)(2)(3)I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter (DAT) positron emission tomography (PET) predicts prognosis in drug-induced Parkinsonism (DIP): a 2-year follow-up study.","volume":"56","author":"J Kim","year":"2013","journal-title":"Archives of gerontology and geriatrics"},{"issue":"3","key":"pone.0247354.ref011","first-page":"552","article-title":"Nigral dysfunction in drug-induced parkinsonism: an 18","volume":"43","author":"D Burn","year":"1993","journal-title":"F-dopa PET study. 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