Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-b95js Total loading time: 0 Render date: 2025-01-09T21:32:15.216Z Has data issue: false hasContentIssue false

Chapter 23 - Continuous Dopaminergic Stimulation in Parkinson’s Disease

from Section 2: - Hypokinetic Movement Disorders

Published online by Cambridge University Press:  07 January 2025

By
Angelo Antonini
Edited by
Erik Ch. Wolters  and
Christian R. Baumann
Erik Ch. Wolters
Affiliation:
Universität Zürich
Christian R. Baumann
Affiliation:
Universität Zürich
Get access

Summary

Continuous dopaminergic stimulation aims to avoid fluctuations in plasma levels of antiparkinsonian drugs in Parkinson’s disease. There are limited possibilities for translating this concept into practice with standard oral therapies: subcutaneous infusions of apomorphine (and in the near future most probably also of levodopa) and intestinal infusions of levodopa/carbidopa (LD/CD). Both allow the maintenance of stable drug levels in blood and hence a sustained stimulation of dopamine receptors. The magnitude of the effect is more or less similar between techniques, with a reduction in OFF time, an improvement in ON time, and at least for infusions of LD/CD, documented reduction in dyskinesias. The effect is apparently greater with the intestinal and subcutaneous levodopa infusions given that they were compared with oral LD/CD in their pivotal studies whereas apomorphine was compared with placebo. As of yet, subcutaneous apomorphine and intestinal LD/CD infusions are positioned at the same level of efficacy as surgical treatment of PD and are alternatives for the treatment of patients with motor fluctuations not controlled with conventional treatment.

Keywords

Continuous dopaminergic stimulationapomorphine infusionlevodopa–carbidopa intestinal gel (LCIG)continuous subcutaneous levodopa infusion
Type
Chapter
Information
International Compendium of Movement Disorders , pp. 280 - 289
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Antonini, A, Odin, P. Pros and cons of apomorphine and L-dopa continuous infusion in advanced Parkinson’s disease. Parkinsonism Relat Disord 2009;15(Suppl 4):S97–100.CrossRefGoogle ScholarPubMed
Poewe, W, Antonini, A. Novel formulations and modes of delivery of levodopa. Mov Disord 2015;30(1):114–120.CrossRefGoogle ScholarPubMed
Olanow, CW, Obeso, JA, Stocchi, F. Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol 2006;5(8):677–687.CrossRefGoogle ScholarPubMed
Deuschl, G, Antonini, A, Costa, J, et al. European Academy of Neurology/Movement Disorder Society–European Section Guideline on the Treatment of Parkinson’s Disease: I. Invasive therapies. Mov Disord 2022;37(7):1360–1374.CrossRefGoogle ScholarPubMed
Katzenschlager, R, Poewe, W, Rascol, O, et al. Long-term safety and efficacy of apomorphine infusion in Parkinson’s disease patients with persistent motor fluctuations: results of the open-label phase of the TOLEDO study. Parkinsonism Relat Disord 2021;83:79–85.CrossRefGoogle ScholarPubMed
Katzenschlager, R, Poewe, W, Rascol, O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2018;17(9):749–759.CrossRefGoogle Scholar
García Ruiz, PJ, Ignacio, ÁS, Pensado, BA, et al. Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease with motor fluctuations: A multicenter study. Mov Disord 2008;23(8):1130–1136.CrossRefGoogle ScholarPubMed
Trenkwalder, C, Chaudhuri, KR, García Ruiz, PJ, et al. Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson’s disease – clinical practice recommendations. Parkinsonism Relat Disord 2015;21(9):1023–1030.CrossRefGoogle Scholar
Borgemeester, RWK, Drent, M, van Laar, T. Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson’s disease patients. Parkinsonism Relat Disord 2016;23:17–22.CrossRefGoogle ScholarPubMed
Sesar, Á, Fernández-Pajarín, G, Ares, B, Rivas, MT, Castro, A. Continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease: 10-year experience with 230 patients. J Neurol 2017;264(5):946–954.CrossRefGoogle ScholarPubMed
Fernández-Pajarín, G, Sesar, Á, Ares, B, Castro, A. Evaluating the efficacy of nocturnal continuous subcutaneous apomorphine infusion in sleep disorders in advanced Parkinson’s disease: the APO-NIGHT study. J Parkinsons Dis 2016;6(4):787–792.CrossRefGoogle ScholarPubMed
Nyholm, D, Nilsson Remahl, AIM, Dizdar, N, et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005;64(2):216–223.CrossRefGoogle ScholarPubMed
Olanow, WC, Kieburtz, K, Odin, P, et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014;13:141–149.CrossRefGoogle ScholarPubMed
Fernandez, HH, Standaert, DG, Hauser, RA, et al. Levodopa–carbidopa intestinal gel in advanced Parkinson’s disease: final 12-month, open-label results. Mov Disord 2015;30(4):500–509.CrossRefGoogle ScholarPubMed
Antonini, A, Poewe, W, Chaudhuri, KR, et al. Levodopa-carbidopa intestinal gel in advanced Parkinson’s: final results of the GLORIA registry. Parkinsonism Relat Disord 2017;45:13–20.CrossRefGoogle ScholarPubMed
Müller, T, van Laar, T, Cornblath, DR, et al. Peripheral neuropathy in Parkinson’s disease: levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord 2013;19(5):501–507.CrossRefGoogle ScholarPubMed
Chang, FCF, Tsui, DS, Mahant, N, et al. 24 h Levodopa–carbidopa intestinal gel may reduce falls and “unresponsive” freezing of gait in Parkinson’s disease. Parkinsonism Relat Disord 2015;21(3):317–320.CrossRefGoogle ScholarPubMed
Cossu, G, Ricchi, V, Pilleri, M, et al. Levodopa–carbidopa intrajejunal gel in advanced Parkinson disease with “on” freezing of gait. Neurol Sci 2015;36(9):1683–1686.CrossRefGoogle Scholar
Morales-Briceño, H, Tsui, D, Griffith, J, et al. “On-state” freezing of gait: insights and treatment with levodopa intestinal gel infusion. Mov Disord 2020;35(5):895–896.CrossRefGoogle ScholarPubMed
Antonini, A, Abbruzzese, G, Berardelli, A, et al. The TANDEM investigation: efficacy and tolerability of levodopa–carbidopa intestinal gel in (LCIG) advanced Parkinson’s disease patients. J Neural Transm (Vienna) 2020;127(6):881–891.CrossRefGoogle ScholarPubMed
Antonini, A, Robieson, WZ, Bergmann, L, Yegin, A, Poewe, W. Age/disease duration influence on activities of daily living and quality of life after levodopa-carbidopa intestinal gel in Parkinson’s disease. Neurodegener Dis Manag 2018;8(3):161–170.CrossRefGoogle ScholarPubMed
Lew, MF, Slevin, JT, Krüger, R, et al. Initiation and dose optimization for levodopa–carbidopa intestinal gel: Insights from phase 3 clinical trials. Parkinsonism Relat Disord 2015;21(7):742–748.CrossRefGoogle ScholarPubMed
Espay, AJ, Morgante, F, Merola, A, et al. Levodopa-induced dyskinesia in Parkinson disease: current and evolving concepts. Ann Neurol 2018;84(6):797–811.CrossRefGoogle ScholarPubMed
Giladi, N, Gurevich, T, Djaldetti, R, et al. ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson’s disease and motor response fluctuations: a randomized, placebo-controlled phase 2 study. Parkinsonism Relat Disord 2021;91:139–145.CrossRefGoogle ScholarPubMed
Poewe, W, Stocchi, F, Arkadir, D, et al. Subcutaneous levodopa infusion for Parkinson’s disease: 1-year data from the open-label BeyoND study. Mov Disord 2021;36(11):2687–2692.CrossRefGoogle ScholarPubMed
www.prnewswire.com/news-releases/neuroderm-announces-highly-positive-results-from-the-pivotal-phase-iii-boundless-trial-evaluating-nd0612-in-parkinsons-disease-patients-with-motor-fluctuations-301715848.htmlGoogle Scholar
Rosebraugh, M, Liu, W, Neenan, M, Facheris, MF. Foslevodopa/foscarbidopa is well tolerated and maintains stable levodopa and carbidopa exposure following subcutaneous infusion. J Parkinsons Dis 2021;11(4):1695–1702.CrossRefGoogle ScholarPubMed
Rosebraugh, M, Voight, EA, Moussa, EM, et al. Foslevodopa/foscarbidopa: a new subcutaneous treatment for Parkinson’s disease. Ann Neurol 2021;90(1):52–61.CrossRefGoogle ScholarPubMed
Soileau, MJ, Aldred, J, Budur, K, et al. Safety and efficacy of continuous subcutaneous foslevodopa–foscarbidopa in patients with advanced Parkinson’s disease: a randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol 2022;21(12):1099–1109.CrossRefGoogle ScholarPubMed
Martinez-Martin, P, Reddy, P, Katzenschlager, R, et al. EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson’s disease. Mov Disord 2015;30(4):510–516.CrossRefGoogle ScholarPubMed
Dafsari, HS, Reddy, P, Herchenbach, C, et al. Beneficial effects of bilateral subthalamic stimulation on non-motor symptoms in Parkinson’s disease. Brain Stimul 2016;9(1):78–85.CrossRefGoogle ScholarPubMed
Volkmann, J, Albanese, A, Antonini, A, et al. Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol 2013;260(11):2701–2714.CrossRefGoogle ScholarPubMed
Timpka, J, Henriksen, T, Odin, P. Non-oral continuous drug delivery techniques in Parkinson’s disease: for whom, when, and how? Mov Disord Clin Pract 2016;3(3):221–229.CrossRefGoogle Scholar
Odin, P, Chaudhuri, KR, Slevin, JTT, et al. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson’s disease: consensus from an international survey and discussion program. Parkinsonism Relat Disord 2015;21(10):1133–1144.CrossRefGoogle ScholarPubMed
Antonini, A, Mancini, F. Continuous dopaminergic stimulation in Parkinson’s disease. In: Wolters, ECh, Baumann, CR, eds. Parkinson Disease and Other Movement Disorders. Motor Behavioural Disorders and Behavioural Motor Disorders. Amsterdam: VU University Press; 2014: 287–302.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×