{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:10:38Z","timestamp":1788876638360,"version":"build-2803163510"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012681","name":"Universit\u00e4tsklinikum K\u00f6ln","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012681","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neural Transm"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tremor is a common and disabling feature of Parkinson\u2019s disease (PD) and often responds suboptimally to oral dopaminergic therapy. This post\u2011hoc analysis evaluated tremor outcomes associated with apomorphine sublingual film (SL\u2011APO) in patients with a tremor\u2011dominant PD phenotype, using data from a 12\u2011week randomised, double\u2011blind, placebo\u2011controlled trial (NCT02469090) and a 12\u2011month open\u2011label study (NCT02542696) conducted in levodopa\u2011responsive patients with OFF episodes. Tremor\u2011dominant phenotype was defined according to Movement Disorder Society\u2013Unified Parkinson\u2019s Disease Rating Scale (MDS\u2011UPDRS) criteria, and tremor severity was assessed using a derived tremor index. In the randomised trial, 31 of 108 patients (28.7%) met tremor\u2011dominant criteria. At Week 12 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910 per group), greater reductions in tremor index scores were observed 30\u00a0min post\u2011dose with SL\u2011APO versus placebo (mean change\u2009\u2212\u20095.3 vs.\u2009\u2212\u20091.1), with an exploratory between\u2011group difference of \u2212\u20094.4 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and an effect size (Cohen\u2019s d) of \u2212\u20091.83. Clinically important improvement occurred more frequently with SL\u2011APO (80%) than placebo (30%), corresponding to an estimated number needed to treat of 1.3. Median time to ON with SL\u2011APO was 13.0\u00a0min. In the open\u2011label study, tremor reductions of 31\u201337% were maintained over 12 months, with responder rates remaining above 70%. These exploratory findings in a small subgroup are consistent with a potential for early and maintained tremor improvement with SL\u2011APO in patients with tremor\u2011dominant PD; however, the results are hypothesis\u2011generating and require prospective confirmation.\n                  <\/jats:p>","DOI":"10.1007\/s00702-026-03225-w","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:46:40Z","timestamp":1788875200000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sublingual apomorphine for Parkinsonian tremor: a post-hoc analysis of pivotal trial data"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-4233","authenticated-orcid":false,"given":"Haidar S.","family":"Dafsari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Strau\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena C.","family":"Brigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Denecke Muhr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel Pijuan","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Holenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"3","key":"3225_CR1","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3233\/jpd-181462","volume":"9","author":"J Angulo","year":"2019","unstructured":"Angulo J, Fleury V, P\u00e9ron JA, Penzenstadler L, Zullino D, Krack P (2019) Shame in Parkinson\u2019S Disease: A Review. J Parkinsons Dis 9(3):489\u2013499. https:\/\/doi.org\/10.3233\/jpd-181462","journal-title":"J Parkinsons Dis"},{"key":"3225_CR2","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"JT Cohen","year":"1988","unstructured":"Cohen JT (1988) Statistical Power Analysis for the Behavioral Sciences, ed 2. Lawrence Earlbaum Associates, Hillsdale","edition":"ed 2"},{"issue":"9","key":"3225_CR3","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1002\/mds.26697","volume":"31","author":"RA Hauser","year":"2016","unstructured":"Hauser RA, Olanow CW, Dzyngel B, Bilbault T, Shill H, Isaacson S, Dubow J, Agro A (2016) Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson\u2019s disease. Mov Disord 31(9):1366\u20131372. https:\/\/doi.org\/10.1002\/mds.26697","journal-title":"Mov Disord"},{"issue":"3","key":"3225_CR4","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1177\/1877718x251329328","volume":"15","author":"RA Hauser","year":"2025","unstructured":"Hauser RA, Skarpaas TC, Merriam A, Rivera J, Hoxhaj V, Barbato LM, Chadha-Patel A, Baladi M (2025) Burden of tremor in Parkinson\u2019s disease: a survey study. J Parkinsons Dis 15(3):541\u2013551. https:\/\/doi.org\/10.1177\/1877718x251329328","journal-title":"J Parkinsons Dis"},{"key":"3225_CR5","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.parkreldis.2020.08.028","volume":"79","author":"JS Hui","year":"2020","unstructured":"Hui JS, Fox SH, Neeson W, Bhargava P, Pappert E, Blum D, Navia B (2020) Open-label titration of apomorphine sublingual film in patients with Parkinson\u2019s disease and OFF episodes. Parkinsonism Relat Disord 79:110\u2013116. https:\/\/doi.org\/10.1016\/j.parkreldis.2020.08.028","journal-title":"Parkinsonism Relat Disord"},{"issue":"Suppl 1","key":"3225_CR6","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1016\/j.parkreldis.2016.12.003","volume":"33","author":"P Jenner","year":"2016","unstructured":"Jenner P, Katzenschlager R (2016) Apomorphine - pharmacological properties and clinical trials in Parkinson\u2019s disease. Parkinsonism Relat Disord 33(Suppl 1):S13\u2013S21. https:\/\/doi.org\/10.1016\/j.parkreldis.2016.12.003","journal-title":"Parkinsonism Relat Disord"},{"issue":"6","key":"3225_CR7","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.1007\/s00415-024-12323-2","volume":"271","author":"J Kassubek","year":"2024","unstructured":"Kassubek J, Factor SA, Balaguer E, Schwarz J, Chaudhuri KR, Isaacson SH, Wu S, Denecke Muhr C, Kulisevsky J (2024a) Long-term safety, tolerability and efficacy of apomorphine sublingual film in patients with Parkinson\u2019s disease complicated by OFF episodes: a phase 3, open-label study. J Neurol 271(6):3554\u20133570. https:\/\/doi.org\/10.1007\/s00415-024-12323-2","journal-title":"J Neurol"},{"issue":"10","key":"3225_CR8","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1007\/s00702-024-02777-z","volume":"131","author":"J Kassubek","year":"2024","unstructured":"Kassubek J, Jost WH, Schwarz J (2024b) Sublingual apomorphine in the treatment of Parkinson\u2019s disease. J Neural Transm (Vienna) 131(10):1209\u20131216. https:\/\/doi.org\/10.1007\/s00702-024-02777-z","journal-title":"J Neural Transm (Vienna)"},{"key":"3225_CR9","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jns.2018.01.013","volume":"386","author":"T Konno","year":"2018","unstructured":"Konno T, Deutschl\u00e4nder A, Heckman MG, Ossi M, Vargas ER, Strongosky AJ, van Gerpen JA, Uitti RJ, Ross OA, Wszolek ZK (2018) Comparison of clinical features among Parkinson\u2019s disease subtypes: a large retrospective study in a single center. J Neurol Sci 386:39\u201345. https:\/\/doi.org\/10.1016\/j.jns.2018.01.013","journal-title":"J Neurol Sci"},{"key":"3225_CR10","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3389\/fneur.2019.00471","volume":"10","author":"JW Lee","year":"2019","unstructured":"Lee JW, Song YS, Kim H, Ku BD, Lee WW (2019) Alteration of Tremor Dominant and Postural Instability Gait Difficulty Subtypes During the Progression of Parkinson\u2019s Disease: Analysis of the PPMI Cohort. Front Neurol 10:471. https:\/\/doi.org\/10.3389\/fneur.2019.00471","journal-title":"Front Neurol"},{"issue":"5","key":"3225_CR11","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1097\/01.Mlr.0000062554.74615.4c","volume":"41","author":"GR Norman","year":"2003","unstructured":"Norman GR, Sloan JA, Wyrwich KW (2003) Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 41(5):582\u2013592. https:\/\/doi.org\/10.1097\/01.Mlr.0000062554.74615.4c","journal-title":"Med Care"},{"issue":"2","key":"3225_CR12","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S1474-4422(19)30396-5","volume":"19","author":"CW Olanow","year":"2020","unstructured":"Olanow CW, Factor SA, Espay AJ, Hauser RA, Shill HA, Isaacson S, Pahwa R, Leinonen M, Bhargava P, Sciarappa K, Navia B, Blum D, investigators CTHS (2020) Apomorphine sublingual film for off episodes in Parkinson\u2019s disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol 19(2):135\u2013144. https:\/\/doi.org\/10.1016\/S1474-4422(19)30396-5","journal-title":"Lancet Neurol"},{"key":"3225_CR13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.5334\/tohm.764","volume":"13","author":"WG Ondo","year":"2023","unstructured":"Ondo WG, Koneru V, Arif C (2023) Task Specific Tremor in Parkinson\u2019s Disease Responds to Apomorphine. Tremor Other Hyperkinet Mov (N Y) 13:20. https:\/\/doi.org\/10.5334\/tohm.764","journal-title":"Tremor Other Hyperkinet Mov (N Y)"},{"key":"3225_CR14","unstructured":"Pappert E, Dzyngel B, Bilbault T, Agro A (2016) Pharmacokinetic-pharmacodynamic effects of apomorphine sublingual film (APL-130277) for the rapid management of OFF episodes in patients with Parkinson\u2019s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https:\/\/www.mdsabstracts.org\/abstract\/pharmacokinetic-pharmacodynamic-effects-of-apomorphine-sublingual-film-apl-130277-for-the-rapid-management-of-off-episodes-in-patients-with-parkinsons-disease\/. Accessed June 2, 2026"},{"issue":"10","key":"3225_CR15","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1002\/mdc3.13845","volume":"10","author":"J Pasquini","year":"2023","unstructured":"Pasquini J, Deuschl G, Pecori A, Salvadori S, Ceravolo R, Pavese N (2023) The Clinical Profile of Tremor in Parkinson\u2019s Disease. Mov Disord Clin Pract 10(10):1496\u20131506. https:\/\/doi.org\/10.1002\/mdc3.13845","journal-title":"Mov Disord Clin Pract"},{"issue":"12","key":"3225_CR16","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1016\/S1474-4422(09)70293-5","volume":"8","author":"MC Rodriguez-Oroz","year":"2009","unstructured":"Rodriguez-Oroz MC, Jahanshahi M, Krack P, Litvan I, Macias R, Bezard E, Obeso JA (2009) Initial clinical manifestations of Parkinson\u2019s disease: features and pathophysiological mechanisms. Lancet Neurol 8(12):1128\u20131139. https:\/\/doi.org\/10.1016\/S1474-4422(09)70293-5","journal-title":"Lancet Neurol"},{"issue":"5","key":"3225_CR17","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1002\/mds.25383","volume":"28","author":"GT Stebbins","year":"2013","unstructured":"Stebbins GT, Goetz CG, Burn DJ, Jankovic J, Khoo TK, Tilley BC (2013) How to identify tremor dominant and postural instability\/gait difficulty groups with the movement disorder society unified Parkinson\u2019s disease rating scale: Comparison with the unified Parkinson\u2019s disease rating scale. Mov Disord 28(5):668\u2013670. https:\/\/doi.org\/10.1002\/mds.25383","journal-title":"Mov Disord"},{"issue":"8","key":"3225_CR18","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.3233\/jpd-230072","volume":"13","author":"F Stocchi","year":"2023","unstructured":"Stocchi F, Rascol O, Poewe W, Chaudhuri KR, Kassubek J, Lopez Manzanares L, Zhang Y, Bowling A, Pappert E, Wu S (2023) Apomorphine Sublingual Film Compared with Subcutaneous Apomorphine for OFF Episodes in Parkinson\u2019s Disease: An Open-Label, Randomized, Crossover Study. J Parkinsons Dis 13(8):1329\u20131342. https:\/\/doi.org\/10.3233\/jpd-230072","journal-title":"J Parkinsons Dis"},{"key":"3225_CR19","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.2147\/ppa.S301644","volume":"15","author":"A Thach","year":"2021","unstructured":"Thach A, Sutphin J, Coulter J, Leach C, Pappert E, Mansfield C (2021) Patient Preferences for Treating OFF Episodes in Parkinson\u2019s Disease: A Discrete Choice Experiment. Patient Prefer Adherence 15:1187\u20131196. https:\/\/doi.org\/10.2147\/ppa.S301644","journal-title":"Patient Prefer Adherence"},{"issue":"11","key":"3225_CR20","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1007\/s00702-025-03042-7","volume":"132","author":"B Yegla","year":"2025","unstructured":"Yegla B, Rubin J, Grall M, Formella A, Jenner P (2025) Apomorphine differentially engages the cAMP and \u03b2-arrestin signaling pathways relative to dopamine at human dopamine receptors. J Neural Transm (Vienna) 132(11):1751\u20131760. https:\/\/doi.org\/10.1007\/s00702-025-03042-7","journal-title":"J Neural Transm (Vienna)"}],"container-title":["Journal of Neural Transmission"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-026-03225-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00702-026-03225-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-026-03225-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:46:42Z","timestamp":1788875202000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00702-026-03225-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":20,"alternative-id":["3225"],"URL":"https:\/\/doi.org\/10.1007\/s00702-026-03225-w","relation":{},"ISSN":["0300-9564","1435-1463"],"issn-type":[{"value":"0300-9564","type":"print"},{"value":"1435-1463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"assertion":[{"value":"20 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Haidar S Dafsari reports consultancy for BIAL. Jo\u00e3o Reis, Kerstin Strau\u00df, Helena C Brigas, Carmen Denecke Muhr, Isabel Pijuan Jim\u00e9nez, and Joerg Holenz are employed by BIAL.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}