Continuous subcutaneous apomorphine monotherapy in Parkinson’s disease
Ewa Papuć 1  
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Department of Neurology, Medical University of Lublin, Poland
Ewa Papuć   

Department of Neurology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland
Ann Agric Environ Med. 2019;26(1):133–137
Introduction and objective:
Continuous subcutaneous apomorphine (APO) treatment is one of the 3 therapeutic options for advanced Parkinson’s disease (PD), in addition to deep brain stimulation (DBS) and intrajejunal levodopa. Data from previously performed studies show that few PD patients can achieve APO infusion as monotherapy. The current pilot study presents the authors’ experience in achieving APO monotherapy.

Material and methods:
During the last 2 years, 9 patients with APO were treated in the Department of Neurology of the Medical University of Lublin; each patient was offered a 5-day duration APO treatment as monotherapy. The main indication for the APO therapy was advanced PD with motor fluctuations and the patient’s non-agreement for DBS therapy. Mean age of treated patients – 65.11 years, mean disease duration – 7.67 years, mean Hoehn-Yahr – 2.67, mean L-dopa equivalent before APO treatment – 1751.11 mg, mean daily dose of apomorphine as monotherapy – 106.11 ± 14.09 mg.

All treated patients managed to achieve APO monotherapy. A statistically significant reduction was found in the duration of the ‘off’ states in the observed PD patients on APO monotherapy (p<0.05). No significant improvement was observed in the III motor score of the UPDRS on APO treatment, compared to optimized oral therapy used before APO treatment.

APO monotherapy can be achieved in advanced PD, and seems to be a good therapeutic option for this group of patients, especially in that it allows a significant reduction in the off-time which significantly simplifies the drug regime. Nevertheless, hospital admission with experienced neurologist supervision is recommended when establishing a PD patient’s APO monotherapy.

Antonini A, Moro E, Godeiro C, Reichmann H. Medical and surgical management of advanced Parkinson’s disease. Mov Disord. Online Early
Jenner P, Katzenschlager R. Apomorphine – pharmacological properties and clinical trials in Parkinson’s disease. Parkinsonism Relat Disord. 2016; 33(Suppl1): 13–21.
Lees AJ. Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fundam Clin Pharmacol. 1993; 7(3–4): 121–128.
Colosimo C, Merello M, Albanese A. Clinical usefulness of apomorphine in movement disorders. Clin Neuropharmacol. 1994; 17(3): 243–259.
Obeso JA, Grandas F, Vaamonde J, Rosario Luguin M, Martínez-Lage JM. Apomorphine infusion for motor fluctuations in Parkinson’s disease. Lancet. 1987; 1(8546): 1376–1377.
Stocchi F, Vacca L, De Pandis MF, Barbato L, Valente M, Ruggieri S. Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson’s disease: long-term results. Neurol Sci. 2001; 22(1): 93–94.
Manson AJ, Turner K, Lees AJ. Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson’s disease: long-term follow-up study of 64 patients. Mov Disord. 2002; 17(6): 1235–1241.
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.
Antonini A, Isaias IU, Rodolfi G , Landi A, Natuzzi F, Siri C, et al. A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation. J Neurol. 2011; 258(4): 579–585.
De Gaspari D, Siri C, Landi A, Cilia R, Bonetti A, Natuzzi F, et al. 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. 2006; 77(4): 450–453.
Martinez-Martin P, Reddy P, Katzenschlager R, Antonini A, Todorova A, Odin P, et al. EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson’s disease. Mov Disord. 2015; 30(4): 510–516.
Katzenschlager R, Poewe W, Rascol O, Trenkwalder C, Deuschl G, Chaudhuri R, et al. Double-blind, randomized, placebo-controlled, Phase III study (TOLEDO) to evaluate the efficacy of apomorphine subcutaneous infusion in reducing OFF time in Parkinson’s disease patients with motor fluctuations not well controlled on optimized conventional treatment. Proceedings of the 21st International Congress of Parkinson’s Disease and Movement Disorders; 2017 June 4–8; Vancouver, Canada. Mov Disord 2017; 32(Suppl 2): 518–519.
Kimber TE, Fang J, Huddy LJ, Thompson PD . Long-term adherence to apomorphine infusion in patients with Parkinson disease: a 10-year observational study. Intern Med J. 2017; 47(5): 570–573.
Borgemeester RW, 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.
Tyne HL, Parsons J, Sinnott A, Fox SH, Fletcher NA, Steiger MJ. A 10 year retrospective audit of long-term apomorphine use in Parkinson’s disease. J Neurol. 2004; 251(11): 1370–1374.
Defer GL, Widner H, Marié RM, Rémy P, Levivier M. Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord. 1999; 14(4): 572–584.
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015; 30(12): 1591–1601.
Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008; 23(15): 2129–2170.
Guy W. Clinical Global Impressions (CGI) Scale, Modified. In: Rush AJ; Task Force for the Handbook of Psychiatric Measures, ed. Handbook of Psychiatric Measures. 1st ed. Washington, DC: American Psychiatric Association; 2000.
Trenkwalder C, Chaudhuri KR, García Ruiz PJ, LeWitt P, Katzenschlager R, Sixel-Döring F, 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.
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.
Antonini A, Tolosa E, Mizuno Y, Yamamoto M, Poewe WH. A reassessment of risks and benefits of dopamine agonists in Parkinson’s disease. Lancet Neurol. 2009; 8(10): 929–937.
Gancher ST, Nutt JG, Woodward WR. Apomorphine infusional therapy in Parkinson’s disease: clinical utility and lack of tolerance. Mov Disord. 1995; 10(1): 37–43.
Gancher S, Nutt J. Tolerance to apomorphine develops and reverses rapidly. Mov Disord. 2010; 25(6): 803–804.
Storch A, Schneider CB, Wolz M, Stürwald Y, Nebe A, Odin P, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology. 2013; 80(9): 800–809.
Alegret M, Valldeoriola F, Martí M, Pilleri M, Junqué C, Rumià J, et al. Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson’s disease. Mov Disord. 2004; 19(12):1463–1469.
Daley DJ, Myint PK, Gray RJ, Deane KH. Systematic review on factors associated with medication non-adherence in Parkinson’s disease. Parkinsonism Relat Disord. 2012; 18(10): 1053–1061.
Chaudhuri KR, Qamar MA, Rajah T, Loehrer P, Sauerbier A, Odin P, et al. Non-oral dopaminergic therapies for Parkinson’s disease: current treatments and the future. NPJ Parkinsons Dis. 2016; 2: 16023.
Todorova A, Chaudhuri KR. Subcutaneous apomorphine and non-motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord. 2013; 19(12): 1073–1078.
Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, et al. Apomorphine treatment in Alzheimer mice promoting amyloid-β degradation. Ann Neurol. 2011; 69(2): 248–256.