PDF herunterladen
psychoneuro 2008; 34(1): 10-22
DOI: 10.1055/s-2008-1061489
Schwerpunkt

© Georg Thieme Verlag Stuttgart · New York

Idiopathisches Parkinson-Syndrom - Update: Pharmaka, aktivierende Therapien und tiefe Hirnstimulation

Update Parkinson's Disease - Pharmacotherapy, activating therapies, deep brain stimulationAndres Ceballos-Baumann1
  • 1Neurologisches Krankenhaus München, Zentrum für Parkinson und Bewegungsstörungen (Ärztliche Leitung: Prof. Dr. A. Ceballos-Baumann)
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
27. Februar 2008 (online)

    Lizenzen und Reprints

Zwei Non-Ergot-Dopaminagonisten - Rotigotin als erstes „Parkinson-Pflaster” und Piribedil - sind seit 2007 sowohl zur Mono- als auch zur Kombinationstherapie mit L-Dopa zugelassen. Hinzu kommt Ropinirol in einer neuen, retardierten Darreichungsform, das nur einmal täglich eingenommen werden muss. Der Einsatz des parenteralen Non-Ergot-Dopaminagonisten Apomorphin als Penject zum bedarfsorientierten Einsatz oder über eine Mikropumpe zur kontinuierlichen subkutanen Infusion bei Off-Phasen wächst und eignet sich auch für Patienten in Warteposition für die tiefe Hirnstimulation. L-Dopa gilt weiterhin als die Referenz in der Parkinsontherapie. Die COMT-Hemmer Entacapon (als Einzel- oder Kombinationspräparat mit L-Dopa/Carbidopa) und Tolcapon wirken nur über eine L-Dopa-Potenzierung und sind für Wearing-off-Phänomene hilfreich. Außerdem etabliert sich ein L-Dopa/Carbidopa-Gel zur kontinuierlichen duodenalen Infusion via perkutaner endoskopischer Gastroektomie für ausgewählte Patienten mit schweren Off-Phasen. Ferner wurde 2005 ein neuer MAO-B-Hemmer, Rasagilin, für alle Phasen des idiopathischen Parkinson-Syndroms (IPS) und 2007 der Cholinesterasehemmer Rivastigimin für die Demenz bei IPS zugelassen. Wesentliche lebensqualitätsbestimmende Symptome wie Sturzneigung, Sprech- und Schluckstörungen lassen sich trotz der vielen Medikamente und der tiefen Hirnstimulation in späten Stadien der Krankheit schlecht behandeln. Hier spielen neue, symptomorientierte aktivierende Therapien eine wesentliche Rolle, deren Konzepte wie z.B. die Stimmtherapie nach Lee Silverman und das Training von Ausgleichsschritten wissenschaftlich etabliert sind. Bei der tiefen Hirnstimulation, deren Ergebnis mit der positiven Wirkung von L-Dopa korreliert, zeichnet sich der Trend ab, eher jüngere Patienten zu operieren.

Two non-ergot dopamine agonists, rotigotine (Neupro®) the first transdermal patch in Parkinson's disease (PD), and piribedil (Clarium®) have been licensed in Germany since 2007 for mono- and levodopa combination therapy. Ropinirole 24-hour prolonged release (Requip® Monotab), another non-ergot dopamine agonist, will be introduced and allow once daily dosing of ropinirol. The non-ergot parenteral dopamine agonist apomorphine available as penject for on demand use or for continuous subcutaneous infusion in patients with off-phases has an important role in patients with in complex motor fluctuations, also for those waiting for deep brain stimulation. Levodopa is still the gold standard in PD therapy. The COMT inhibitors entacapone (Comtess® or in Stalevo® as triple combination with levodopa/carbidopa) and tolcapone (Tasmar®) work only by increasing the bioavailability of levodopa and are helpful for wearing-off phenomena. Levodopa/carbidopa as a gel (Duodopa®) for continuous dudodenal infusion via PEG represents an alternative to the apomorphine pump for seleceted patients. Furthermore, in 2005 a new MAO-B inhibitor, rasagiline (Azilect®), was licensed for all PD stages and in 2007 a cholinesterase inhibitor rivastigimin (Exelon®) for PD associated dementia. However, essential quality of life determining parkinsonian symptoms such as falls, voice and swallowing symptoms are difficult to treat despite the many new drugs and deep brain stimulation (DBS). New activating therapy concepts are emerging for medication and DBS refractory symptoms, which will be increasingly evidence based such as the Lee Silverman Voice Treatment (LSVT®) and the repetitive training of compensatory steps. In DBS of the subthalamic nucleus there is a trend to operate in earlier stages of the disease course than before as the magnitude of postoperative quality of life improvement occurs mainly in young patients.

Key words

Parkinson's disease - pharmacotherapy - activating therapy - deep brain stimulation - L-Dopa

Literatur

  • 1 Biglan KM. et al. . Parkinson Study Group CALM-PD Investigators. Risk factors for somnolence, edema, and hallucinations in early Parkinson disease.  Neurology. 2007;  69 187-195
    CrossrefPubMedGoogle Scholar
  • 2 Biglan KM. et al. . Rasagiline improves quality of life in patients with early Parkinson's disease.  Mov Disord. 2006;  21 616-623
    CrossrefPubMedGoogle Scholar
  • 3 Burkhard PR. et al. . Suicide after successful deep brain stimulation for movement disorders.  Neurology. 2004;  63 2170-2172
    CrossrefPubMedGoogle Scholar
  • 4 Castro-Caldas A. et al. . The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.  Mov Disord. 2006;  21 500-509
    CrossrefPubMedGoogle Scholar
  • 5 Ceballos-Bauman AO.. Apomorphin bei idiopathischem Parkinson-Syndrom.  Akt Neurol. 2005;  32
    PubMedGoogle Scholar
  • 6 Ceballos-Bauman A, Ebersbach G.. Aktivierende Therapien bei Parkinson-Syndromen. Stuttgart: Thieme 2008
    Google Scholar
  • 7 Chan PL. et al. . Levodopa slows progression of Parkinson's disease: external validation by clinical trial simulation.  Pharm Res. 2007;  24 791-802
    CrossrefPubMedGoogle Scholar
  • 8 Derost PP. et al. . Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population?.  Neurology. 2007;  68 1345-1355
    CrossrefPubMedGoogle Scholar
  • 9 Deutschl G. et al. . A randomized trial of deep-brain stimulation for Parkinson's disease.  N Engl J Med. 2006;  355 896-908
    CrossrefPubMedGoogle Scholar
  • 10 Dodd ML. et al. . Pathological gambling caused by drugs used to treat Parkinson disease.  Arch Neurol. 2005;  62 1377-1381
    CrossrefPubMedGoogle Scholar
  • 11 Eggert K. et al. . Herzklappenerkrankungen und andere fibrotische Reaktionen als Nebenwirkung von Dopamin-Agonisten: Klinische Konsequenzen beim jetzigen Stand (8/2004) der Erkenntnisse.  DÄB. 2005;  102
    PubMedGoogle Scholar
  • 12 Emre M. et al. . Rivastigmine for dementia associatied with Parkinson's disease.  N Engl J Med. 2004;  351 2509-2518
    CrossrefPubMedGoogle Scholar
  • 13 The Entacapone to Tolcapone Switch Study Investigators. . Entacapone to tolcapone switch: Multicenter double-blind, randomized, active-controlled trial in advanced Parkinson's disease.  Mov Disord. 2007;  22 14-19
    CrossrefPubMedGoogle Scholar
  • 14 Fahn S. et al. . Levodopa and the progression of Parkinson's disease.  N Engl J Med. 2004;  351 2498-2508
    CrossrefPubMedGoogle Scholar
  • 15 Farley BG, Koshland GF.. Training BIG to move faster: the application of the speed-amplitude relation as a rehabilitation strategy for people with Parkinson's disease.  Exp Brain Res. 2005;  167 462-467
    CrossrefPubMedGoogle Scholar
  • 16 Fisher BE. et al. . Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia.  J Neurosci Res. 2004;  77
    PubMedGoogle Scholar
  • 17 Fox CM. et al. . The science and practice of LSVT/LOUD: neural plasticity-principled approach to treating individuals with Parkinson disease and other neurological disorders.  Semin Speech Lang. 2006;  27 283-299
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 18 Funkiewiez A. et al. . Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 834-839
    CrossrefPubMedGoogle Scholar
  • 19 Grazko MA. et al. . Botulinum toxin A for spasticity, muscle spasms, and rigidity.  Neurology. 1995;  45 712-717
    PubMedGoogle Scholar
  • 20 Henningsen P. et al. .Neuro-Psychosomatik. Stuttgart: Schattauer Verlag 2006
    Google Scholar
  • 21 Jobges M. et al. . Repetitive training of compensatory steps: a therapeutic approach for postural instability in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 1682-1687
    CrossrefPubMedGoogle Scholar
  • 22 Katzenschlager R. et al. . Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson's disease: a prospective study using single-dose challenges.  Mov Disord. 2005;  20 151-157
    CrossrefPubMedGoogle Scholar
  • 23 Keus SH. et al. . Practice Recommendations Development Group. Evidence-based analysis of physical therapy in Parkinson's disease with recommendations for practice and research.  Mov Disord. 2007;  22
    PubMedGoogle Scholar
  • 24 Lagalla G. et al. . Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study.  Mov Disord. 2006;  21 704-707
    CrossrefPubMedGoogle Scholar
  • 25 Lees AJ. et al. . Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2007;  78 944-948
    CrossrefPubMedGoogle Scholar
  • 26 Maidment I. et al. . Cholinesterase inhibitors for Parkinson's disease dementia.  Cochrane Database Syst Rev. 2006;  1
    PubMedGoogle Scholar
  • 27 de Marcaida JA. et al. . Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline.  Mov Disord. 2006;  21 1716-1721
    CrossrefPubMedGoogle Scholar
  • 28 Müller J. et al. . Botulinum toxin treatment in atypical parkinsonian disorders associated with disabling focal dystonia.  J Neurol. 2002;  249 300-304
    PubMedGoogle Scholar
  • 29 Nyholm D. et al. . Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease.  Neurology. 2005;  64 216-623
    CrossrefPubMedGoogle Scholar
  • 30 Pacchetti C. et al. . „Off” painful dystonia in Parkinson's disease treated with botulinum toxin.  Mov Disord. 1995;  10 333-336
    CrossrefPubMedGoogle Scholar
  • 31 Pahwa R. et al. . Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease.  Neurology. 2007;  68 1108-1115
    CrossrefPubMedGoogle Scholar
  • 32 Parkinson Study Group. . A controlled trial of rotigotine monotherapy in early Parkinson's disease.  Arch Neurol. 2003;  60 1721-1728
    CrossrefPubMedGoogle Scholar
  • 33 Parkinson Study Group. . A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.  Arch Neurol. 2004;  61 561-566
    CrossrefPubMedGoogle Scholar
  • 34 Pinto S. et al. . Treatments for dysarthria in Parkinson's disease.  Lancet Neurol. 2004;  3 547-556
    CrossrefPubMedGoogle Scholar
  • 35 Poewe WH. et al. . Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial.  Lancet Neurol. 2007;  6 513-520
    CrossrefPubMedGoogle Scholar
  • 36 Pontone G. et al. . Clinical features associated with impulse control disorders in Parkinson disease.  Neurology. 2006;  67 1258-1261
    CrossrefPubMedGoogle Scholar
  • 37 Ramig LO. et al. . Intensive voice treatment (LSVT) for patients with Parkinson's disease: a 2 year follow up.  J Neurol Neurosurg Psychiatry. 2001;  71 493-498
    CrossrefPubMedGoogle Scholar
  • 38 Rascol O. et al. . Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.  Lancet. 2003;  365 947-954
    PubMedGoogle Scholar
  • 39 Rascol O. et al. . Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.  Mov Disord. 2006;  21 2110-2115
    CrossrefPubMedGoogle Scholar
  • 40 Schade R. et al. . Dopamine agonists and the risk of cardiac-valve regurgitation.  N Engl J Med. 2007;  356 29-38
    CrossrefPubMedGoogle Scholar
  • 41 Schrag A.. Entacapone in the treatment of Parkinson's disease.  Lancet Neurol. 2005;  4 366-370
    PubMedGoogle Scholar
  • 42 Schüpbach M. et al. . Neurosurgery in Parkinson disease: a distressed mind in a repaired body?.  Neurology. 2006;  66 1811-1816
    CrossrefPubMedGoogle Scholar
  • 43 Schüpbach WM. et al. . Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial.  Neurology. 2007;  68 267-271
    CrossrefPubMedGoogle Scholar
  • 44 Smeding HM. et al. . Neuropsychological effects of bilateral STN stimulation in Parkinson disease: a controlled study.  Neurology. 2006;  66 1830-1836
    CrossrefPubMedGoogle Scholar
  • 45 Voon V. et al. . Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease.  Arch Neurol. 2007;  64 212-216
    CrossrefPubMedGoogle Scholar
  • 46 Weintraub D. et al. . Association of dopamine agonist use with impulse control disorders in Parkinson disease.  Arch Neurol. 2006;  63 969-973
    CrossrefPubMedGoogle Scholar
  • 47 Zanettini R. et al. . Valvular heart disease and the use of dopamine agonists for Parkinson's disease.  N Engl J Med. 2007;  356 39-46
    CrossrefPubMedGoogle Scholar

Korrespondenz

Prof. Dr. med. Andres Ceballos-Baumann

Neurologisches Krankenhaus München Zentrum für Parkinson und Bewegungsstörungen

Parzivalplatz 4

80804 München

eMail: andres.ceballos-baumann@nk-m.de

      >