Continuous subcutaneous apomorphine in advanced Parkinson’s disease patients treated with deep brain stimulation

  • Ángel Sesar
  • Gustavo Fernández-Pajarín
  • Begoña Ares
  • José-Luis Relova
  • Eduardo Arán
  • María-Teresa Rivas
  • Miguel Gelabert-González
  • Alfonso Castro
Original Communication



Deep brain stimulation (DBS) is an effective therapy for patients with advanced Parkinson’s disease (PD). However, sometimes, it is not sufficient to adequately control motor symptoms. We describe our experience with continuous subcutaneous apomorphine infusion (APO) in patients with DBS.


We undertook a retrospective analysis of all patients treated with DBS and APO at our centre over 12 years. Subjects were allocated to four groups: (1) APO temporarily before DBS, (2) APO after DBS complications before a new DBS, (3) APO after definitive DBS removal, and (4) APO in patients with DBS and declining response. Motor state and other parameters were analysed and compared for the different treatments.


Data for 71 patients were evaluated. Group 1: (n = 18) patients improved their motor function significantly with both APO and DBS (off-hours before APO 5.4 ± 1.4; after APO 1.4 ± 1.2, p > 0.001; after DBS 0.7 ± 0.8, p < 0.001). Group 2: (n = 11) patients were found to have mild but significant worsening of motor state between the first DBS treatment (off-hours 0.7 ± 1.0) and APO (2.2 ± 1.5, p = 0.02), and improvement between APO and the second DBS treatment (off-hours 0.6 ± 0.8, p = 0.03). Group 3: (n = 12) patients had mild but significant worsening of motor function between DBS (off-hours 1.1 ± 1.0) and APO (2.0 ± 0.9, p = 0.03). Group 4: (n = 13) significant improvement in motor function was observed between DBS alone (off-hours 3.9 ± 2.6) and DBS combined with APO (2.2 ± 1.3, p = 0.03).


In advanced PD, DBS may be not sufficient or may fail to control motor symptoms adequately. In these cases, APO, whether alone or in combination with DBS, is a good choice to improve the disease control.


Advanced Parkinson’s disease Deep brain stimulation Apomorphine Treatment 


Author Contributions

ÁS: conception, design, analysis and interpretation of data, drafting, review, and final approval. GF-P: design, acquisition of data, analysis, and interpretation of data, critical review, and final approval. BA: design, acquisition of data, critical review, and final approval. JLR: critical review and final approval. EA: critical review and final approval. MTR: critical review and final approval. MG: critical review and final approval. AC: acquisition of data, critical review, and final approval.


The study did not receive funding.

Compliance with ethical standards

Conflicts of interest

ÁS has received honoraria from Britannia/Italfarmaco, and Abbvie; GFP from Italfarmaco and UCB; BA from Italfarmaco and Abbvie; AC from Abbvie and Zambon; MTR, JLR, EA, and MG have no conflicts of interest.

Ethical standards

This study was performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Since this is a retrospective clinical study, no informed consent was required.

Supplementary material

415_2019_9184_MOESM1_ESM.docx (29 kb)
Supplementary material 1 (DOCX 28 KB)


  1. 1.
    Martinez-Martin P, Kulisevsky J, Mir P, Tolosa E, García-Delgado P, Luquin MR (2018) Validation of a simple screening tool for early diagnosis of advanced Parkinson’s disease in daily practice: the CDEPA questionnaire. NPJ Parkinsons Dis 4:20. CrossRefGoogle Scholar
  2. 2.
    Benabid AL, Chabardes S, Mitrofanis J, Pollak P (2009) Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol 8:67–81. CrossRefGoogle Scholar
  3. 3.
    Pollak P (2013) Deep brain stimulation for Parkinson’s disease—patient selection. Handb Clin Neurol 116:97–105. CrossRefGoogle Scholar
  4. 4.
    Katzenschlager R, Poewe W, Rascol O, Trenkwalder C, Deuschl G, Chaudhuri KR, Henriksen T, van Laar T, Spivey K, Vel S, Staines H, Lees A (2018) Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 17:749–759. CrossRefGoogle Scholar
  5. 5.
    Auffret M, Drapier S, Vérin M. Pharmacological insights into the use of apomorphine in Parkinson’s disease: clinical relevance (2018). Clin Drug Investig 38: 287–312.
  6. 6.
    Nyholm D. Duodopa® treatment for advanced Parkinson’s disease: a review of efficacy and safety (2012). Parkinsonism Relat Dis 18: 916–929
  7. 7.
    Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A; LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study (2014). Lancet Neurol 13: 141–149.
  8. 8.
    Ray Chaudhuri K, Qamar MA, Rajah T, Loehrer P, Sauerbier A, Odin P, Jenner P (2016) Non-oral dopaminergic therapies for Parkinson’s disease: current treatments and the future. NPJ Parkinsons Dis 2:16023. CrossRefGoogle Scholar
  9. 9.
    Defer GL, Widner H, Marie RM, Remy P, Levivier M (1999) Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord 14:572–584CrossRefGoogle Scholar
  10. 10.
    Volkmann J, Albanese A, Antonini A, Chaudhuri KR, Clarke CE, de Bie RM, Deuschl G, Eggert K, Houeto JL, Kulisevsky J, Nyholm D, Odin P, Østergaard K, Poewe W, Pollak P, Rabey JM, Rascol O, Ruzicka E, Samuel M, Speelman H, Sydow O, Valldeoriola F, van der Linden C, Oertel W (2013) Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol 260:2701–2714. CrossRefGoogle Scholar
  11. 11.
    Sesar Á, Fernández-Pajarín G, Ares B, Rivas MT, Castro A (2017) Continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease: 10-year experience with 230 patients (2017). J Neurol 264:946–954. CrossRefGoogle Scholar
  12. 12.
    R Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna.
  13. 13.
    Fernández-Pajarín G, Sesar A, Ares B, Relova JL, Arán E, Gelabert-González M, Castro A (2017) Delayed complications of deep brain stimulation: 16-year experience in 249 patients. Acta Neurochir (Wien) 159:1713–1719. CrossRefGoogle Scholar
  14. 14.
    Slotty PJ, Wille C, Kinfe TM, Vesper J (2014) Continuous perioperative apomorphine in deep brain stimulation surgery for Parkinson’s disease. Br J Neurosurg 28:378–382. CrossRefGoogle Scholar
  15. 15.
    Martins de Campos A, Braz L, Linhares P, Rosas MJ (2017) Deep brain stimulation for Parkinson’s disease: subcutaneous apomorphine as an alternative for patients unable to tolerate surgery under local anesthesia. J Neurol Sci 378:137–139. CrossRefGoogle Scholar
  16. 16.
    Carron R, Fraix V, Maineri C, Seigneuret E, Piallat B, Krack P, Pollak P, Benabid AL, Chabardès S (2011) High frequency deep brain stimulation of the subthalamic nucleus versus continuous subcutaneous apomorphine infusion therapy: a review. J Neural Transm (Vienna) 118915:924. Google Scholar
  17. 17.
    Varma TR, Fox SH, Eldridge PR, Littlechild P, Byrne P, Forster A, Marshall A, Cameron H, McIver K, Fletcher N, Steiger M (2003) Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson’s disease patients previously reliant on apomorphine. J Neurol Neurosurg Psychiatry 74:170–174CrossRefGoogle Scholar
  18. 18.
    De Gaspari D, Siri C, Landi A, Cilia R, Bonetti A, Natuzzi F, Morgante L, Mariani CB, Sganzerla E, Pezzoli G, Antonini A (2006) Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson’s disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus. J Neurol Neurosurg Psychiatry 77:450–453. CrossRefGoogle Scholar
  19. 19.
    Alegret M, Valldeoriola F, Martí M, Pilleri M, Junqué C, Rumià J, Tolosa E (2004) Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson’s disease. Mov Disord 19:1463–1469. CrossRefGoogle Scholar
  20. 20.
    Antonini A, Isaias IU, Rodolfi G, Landi A, Natuzzi F, Siri C, Pezzoli G (2011) A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation. J Neurol 258:579–585. CrossRefGoogle Scholar
  21. 21.
    Borgemeester RW, Drent M, van Laar T Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson’s disease patients (2016). Parkinsonism Relat Disord 23: 17–22.
  22. 22.
    Regidor I, Benita V, Del Álamo de Pedro M, Ley L, Martinez Castrillo JC (2017) Duodenal levodopa infusion for long-term deep brain stimulation-refractory symptoms in advanced Parkinson disease. Clin Neuropharmacol 40:103–107. CrossRefGoogle Scholar
  23. 23.
    Juhász A, Deli G, Aschermann Z, Janszky J, Harmat M, Makkos A, Kovács M, Komoly S, Balás I, Dóczi T, Büki A, Kovács N (2017) How efficient is subthalamic deep brain stimulation in reducing dyskinesia in Parkinson’s disease? Eur Neurol 77:281–287. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Servicio de NeurologíaHospital Clínico Universitario Santiago de CompostelaSantiago de CompostelaSpain
  2. 2.Servicio de NeurofisiologíaHospital Clínico Universitario Santiago de CompostelaSantiago de CompostelaSpain
  3. 3.Servicio de NeurocirugíaHospital Clínico Universitario Santiago de CompostelaSantiago de CompostelaSpain

Personalised recommendations