Stellenwert von L-Dopa in der Therapie der Parkinson-Krankheit

Zusammenfassung

Dopaminersatzstrategien sind die tragende Säule der pharmakologischen Behandlung der Parkin-son-Krankheit. Zur Verfügung stehen L-Dopa, Dopamin-Agonisten (DA) und Hemmstoffe des Do-pamin-Abbaus (Mono-aminooxydase-B- und Catechol-O-methyl-transferase-Hemmer). Amantadin und Budipin wirken vorwiegend als NMDA-Rezeptorantagonisten modulieren u. a. aber auch die Dopaminfreisetzung. Während der Einsatz von L-Dopa gegenüber den DA aufgrund des Auf-tretens motorischer Komplikationen und neurotoxischer Effekte kritisch diskutiert wurde, legen die ELLdopa-Studie und Langzeituntersuchungen nahe, den Stellenwert der L-Dopa-Therapie neu zu bewerten. Der Einsatz von L-Dopa und DA (wie der anderen Substanzen auch) muss sich an den individuellen Patientenbedürfnissen und dem Wirkungs- und Nebenwirkungsprofil orientieren. Ziel ist es, Symptome so zu beherrschen, dass berufliche Kompetenz und soziale Selbstständigkeit mit möglichst wenig Nebenwirkungen erhalten werden. Eine klare Empfehlung zur Therapieeinleitung kann nicht pauschal für alle Patienten gegeben werden. Studiendaten für die Wirksamkeit einer Kombination aus DA, MAO_B-Hemmer und Amantadin oder Budipin fehlen. Das Risiko, Dyskinesien zu entwickeln, wird nicht nur durch die L-Dopa-Dosis, sondern auch durch Erkrankungsalter, Geschlecht und Körpergewicht sowie durch unbekannte hereditäre Komponenten beeinflusst. Patienten, die im Verlauf der Erkrankung wahrscheinlich motorische Komplikationen erleben könnten, sollten vorzugsweise mit DA behandelt werden, eine frühe Kombinationstherapie mit L-Dopa (< 400 mg Tagesdosis) erhöht das Dyskinesierisiko nur moderat. Der Stellenwert von L-Dopa steigt mit zunehmendem Alter und Schwere der motorischen Symptomatik sowie bei Vorliegen von Risikofaktoren für Impulskontrollstörungen.

Abstract

Dopamine substitution strategies are the main component of the pharmacotherapy of Parkinson’s disease. Available drugs include levodopa, dopamine agonists (DA) and inhibitors of dopamine degradation (monoaminooxidase B and catechol-O-methyl-transferase inhibitors). Amantadine and budipine primarily act as NMDA receptor Antagonists, but among other (also anticholinergic) effects modulate Dopamine levels. The use of levodopa has been the subject of critical discussions due to the increased occurrence of motor complications and putative neurotoxic effects. However, the ELLdopa trial and other long-term trials suggest that levodopa therapy should be reassesed. The use of levodopa and various DAs (as well as other substances) must be adapted to the requirements of the individual patient and the side effect profiles. The aim is to control the symptoms to such an extent that professional and social self-sufficiency can be maintained with as few side effects as possible. Recommendations how to start therapy cannot be given for all patients equally well. Trial data on the efficacy of combinations of DA, MAO_B inhibitors and amantadine or budipine are lacking. The risk to develop dyskinesias is associated not only with levodopa dosage, but also with disease onset and probably gender and body weight as well as with still unknown hereditary components. Patients who are likely to experience motor complications in the disease course should be treated preferentially with DA, however a combination therapy with levodopa (< 400 mg daily dose) seems to increase daskinesia risk only modestly. The utility of levodopa increases with increasing age and severity of motor symptoms as well as in the presence of risk factors for impulse control disorders.

Schlüsselwörter

Levodopa - Dykinesien - Langzeitnutzen - Dopaminagonisten

Keywords

levodopa - dykinesia - long-term benefit - dopamine agonists

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