Apomorphintherapie bei idiopathischem Parkinson-Syndrom

Zusammenfassung

Apomorphin stellt in vielen Ländern die Standardtherapie für schwer zu beeinflussende Off-Phasen bei idiopathischem Parkinson-Syndrom (IPS) dar. Diese Indikation beinhaltet auch mit Off-Phasen assoziierte Schmerzen, Panikattacken, Schluckstörungen sowie Blasenentleerungs- und Defäkationsstörungen. Doppelblinde Studien zeigen, dass die subkutane Verabreichung von 1 - 5 mg Apomorphin innerhalb von 10 Minuten eine motorische Besserung herbeiführen kann, die in ihrer Ausprägung vergleichbar oder deutlicher als mit L-Dopa ist und bis zu zwei Stunden anhält. Diese Übersicht dient der praktischen Information zu zwei Arten der subkutanen Apomorphinverabreichung: 1. dem Off-Symptom-orientierten Einsatz mittels Apomorphin-Pen von dem gelegentlichen Einsatz bis hin zu 10 Injektionen am Tag. 2. der kontinuierlichen subkutanen Dauerinfusion mittels einer tragbaren Minipumpe. Es werden behandelt: (i) Patientenselektion und -schulung, (ii) die Notwendigkeit der begleitenden Domperidonverabreichung zur Antiemesis, die viele Patienten nach kurzer Zeit nicht mehr benötigen, (iii) die Apomorphindosistitration, (iv) die Behandlung der unerwünschten Wirkungen und (v) Apomorphin versus andere Therapien (symptomorientierte L-Dopa-Darreichungen, tiefe Hirnstimulation, kontinuierliche duodenale L-Dopa-Infusion). Apomorphin sollte bei Patienten mit eindeutigem Ansprechen auf L-Dopa erwogen werden, die über eine unzuverlässige oder zu langsame Wirkung von zusätzlichen symptomorientierten L-Dopa-Dosen klagen.

Abstract

Apomorphine has become a standard rescue therapy for intractable „off” periods in Parkinson's disease (PD). This includes a variety of „off” phenomena, such as pain, panic attacks, and off period associated difficulties in swallowing, micturition and defaecation. Double-blind studies with subcutaneous injection doses of 1 to 5 mg have demonstrated that onset of clinical benefit typically occurs within 10 minutes, and lasts for up to two hours. The motor effect is similar in magnitude to that of levodopa (L-Dopa). This review provides practical information for application of apomorphine subcutaneous therapy in two modalities: 1. either as intermittent off-symptom orientated penject use analogous to rescue doses of levodopa or 2. as continuous subcutaneous infusion via a mini-pump. The publication addresses patient selection and education, the need for concomitant domperidone administration for antiemesis which for many patients wanes over time, apomorphine dosage titration and care of side-effect. Alternative treatments for apomorphine injectable such as sophisticated levodopa rescue dosing for the penject, and deep brain stimulation and continuous duodenal levodopa for the pump will be discussed. The use of apomorphine should be considered in patients with a clear cut response to levodopa who complain of unreliable or slow responses to additional rescue doses of levodopa in off-phases.

Literatur

• 1 Struppler A, Uexkuell T von. Untersuchungen über die Wirkungsweise von Apomorphine auf den Parkinsontremor.  Z Klin Med. 1953;  152 46-57
• 2 Cotzias G C. et al . Similarities between neurological effects of L-dopa and apomorphine.  New Eng J Med. 1970;  282 31-33
• 3 Hughes A J, Lees A J, Stern G M. Challenge tests to predict the dopaminergic response in untreated Parkinson's disease.  Neurology. 1991;  41 1723-1725
• 4 Factor S A, Brown D L, Molho E S. Subcutaneous apomorphine injections as a treatment for intractable pain in Parkinson's disease.  Mov Disord. 2000;  15 167-169
• 5 Reuter I, Ellis C M, Ray Chaudhuri K. Nocturnal subcutaneous apomorphine infusion in Parkinson's disease and restless legs syndrome.  Acta Neurol Scand. 1999;  100 163-167
• 6 Tison F, Wiart L, Guatterie M. et al . Effects of central dopaminergic stimulation by apomorphine on swallowing disorders in Parkinson's disease.  Mov Disord. 1996;  11 729-732
• 7 Kempster P A, Lees A J, Crichton P. et al . Off-period belching due to a reversible disturbance of oesophageal motility in Parkinson's disease and its treatment with apomorphine.  Mov Disord. 1989;  4 47-52
• 8 Bailbe M, Bataille B, Paquereau J. et al . Improvement in swallowing difficulties treated by subcutaneous apomorphine infusion after deep brain stimulation in Parkinson's disease.  Rev Neurol (Paris). 2004;  160 352-353
• 9 Christmas T J, Kempster P A, Chapple C R. et al . Role of subcutaneous apomorphine in parkinsonian voiding dysfunction.  Lancet. 1988;  2 1451-1453
• 10 Edwards L L, Quigley E M, Harned R K. et al . Defecatory function in Parkinson's disease: response to apomorphine.  Ann Neurol. 1993;  33 490-493
• 11 Rosa A E Di, Epifanio A, Antonini A. et al . Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson's disease.  Neurol Sci. 2003;  24 174-175
• 12 Sigurdardottir G R, Nilsson C, Odin P, Grabowski M. Cardiovascular effects of domperidone in patients with Parkinson's disease treated with apomorphine.  Acta Neurol Scand. 2001;  104 92-96
• 13 Corsini G U, Zompo M Del, Gessa G L, Mangoni A. Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease.  Lancet. 1979;  1 954-956
• 14 Stibe C M, Lees A J, Kempster P A, Stern G M. Subcutaneous apomorphine in parkinsonian on-off oscillations.  Lancet. 1988;  1 403-406
• 15 Poewe W, Wenning G K. Apomorphine: an underutilized therapy for Parkinson's disease.  Mov Disord. 2000;  15 789-794
• 16 Manson A J, Hanagasi H, Turner K. et al . Intravenous apomorphine therapy in Parkinson's disease: clinical and pharmacokinetic observations.  Brain. 2001;  124 331-340
• 17 Dewey Jr R B, Hutton J T, LeWitt P A, Factor S A. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events.  Arch Neurol. 2001;  58 1385-1392
• 18 Manson A J, Turner K, Lees A J. 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 1235-1241
• 19 Katzenschlager R, Hughes A, Evans A. et al . Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson's disease: A prospective study using single-dose challenges.  Mov Disord. 2004;  20 151-157
• 20 Tyne H L, Parsons J, Sinnott A. et al . A 10 year retrospective audit of long-term apomorphine use in Parkinson's disease.  J Neurol. 2004;  251 1370-1374
• 21 Colzi A, Turner K, Lees A J. Continuous subcutaneous waking day apomorphine in the long-term treatment of levodopa induced interdose dyskinesias in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 1998;  64 573-576
• 22 Pietz K, Hagell P, Odin P. Subcutaneous apomorphine in late stage Parkinson's disease: A long-term follow-up.  J Neurol Neurosurg Psychiatry. 1998;  65 709-716
• 23 Lees A, Turner K. Apomorphine for Parkinson's disease.  Practical Neurology. 2002;  2 280-286
• 24 Acland K M, Churchyard A, Fletcher C L. et al . Panniculitis in association with apomorphine infusion.  Br J Dermatol. 1998;  138 480-482
• 25 Pinter M M, Helscher R J, Mundsperger N, Binder H. Transient increase of pancreatic enzymes evoked by apomorphine in Parkinson's disease.  J Neural Transm. 1998;  105 1237-1244
• 26 Ceballos-Baumann A O, Kummer R von, Eckert W, Weicker H. Controlled-release levodopa/benserazide (Madopar HBS): Clinical observations and levodopa and dopamine plasma concentrations in fluctuating parkinsonian patients.  J Neurol. 1990;  237 24-28
• 27 Nilsson D, Nyholm D, Aquilonius S M. Duodenal levodopa infusion in Parkinson's disease-long-term experience.  Acta Neurol Scand. 2001;  104 343-348
• 28 Kurth M C, Tetrud J W, Tanner C M. et al . Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson's disease patients with „on-off” fluctuations.  Neurology. 1993;  43 1698-1703
• 29 Sage J I, Trooskin S, Sonsalla P K. et al . Long-term duodenal infusion of levodopa for motor fluctuations in parkinsonism.  Ann Neurol. 1988;  24 87-89
• 30 Kurlan R, Nutt J G, Woodward W R. et al . Duodenal and gastric delivery of levodopa in parkinsonism.  Ann Neurol. 1988;  23 589-595
• 31 Kurlan R, Rubin A J, Miller C. et al . Duodenal delivery of levodopa for on-off fluctuations in parkinsonism: preliminary observations.  Ann Neurol. 1986;  20 262-265
• 32 Charles P D, Blercom N Van, Krack P. et al . Predictors of effective bilateral subthalamic nucleus stimulation for PD.  Neurology. 2002;  59 932-934
• 33 Deep Brain Stimulation for Parkinson's Disease Study Group . Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease.  N Engl J Med. 2001;  345 956-963
• 34 Krack P, Batir A, Blercom N Van. et al . Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease.  N Engl J Med. 2003;  349 1925-1934
• 35 Houeto J L, Mesnage V, Mallet L. et al . Behavioural disorders, Parkinson's disease and subthalamic stimulation.  J Neurol Neurosurg Psychiatry. 2002;  72 701-707