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Fortschr Neurol Psychiatr 2012; 80(3): 130-140
DOI: 10.1055/s-0031-1273223
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Psychostimulantien und Nicht-Stimulantien in der heutigen und zukünftigen ADHS-Therapie

Stimulant and Non-Stimulant Medication in Current and Future Therapy for ADHDA. G. Franke1 , A. Konrad1 , K. Lieb1 , M. Huss2
  • 1Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin Mainz
  • 2Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie, Universitätsmedizin Mainz
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Publication History

Publication Date:
24 May 2011 (online)

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Zusammenfassung

Die gegenwärtige Pharmakotherapie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) basiert im Wesentlichen auf dem Psychostimulans Methylphenidat und in geringem Maße – nicht in Deutschland zugelassen – auf Amphetaminen. Als einziges Nicht-Stimulans ist Atomoxetin (Strattera®) als Noradrenalin-Wiederaufnahme-Hemmer zur Behandlung der ADHS zugelassen. Die Substanzen sind allerdings nur zur Pharmakotherapie der ADHS im Kindes- und Jugendalter zugelassen. Die rein symptomatische Pharmakotherapie zielt auf eine Verbesserung der drei ADHS-Kernsymptome Konzentrationsstörungen, Impulsivität und motorische Unruhe ab. Neurobiologische Korrelate der Therapieeffekte sind weiterhin nicht umfangreich aufgeklärt. Bekannt ist mittlerweile die Wirkung auf dopaminerge und noradrenerge Regelkreise. Probleme in der Anwendung der etablierten Substanzen ergeben sich durch kurze Halbwertszeiten der Psychostimulantien, dem noch nicht vollends aufgeklärten Wirkmechanismus, und der strittigen Anwendung von Stimulantien bei den noch in der Entwicklung befindlichen Kindern und Jugendlichen. Viel diskutiert, jedoch nicht hinreichend belegt ist zudem das Abhängigkeits- und Missbrauchspotenzial der Stimulantien. Die neu zur Verfügung stehenden Substanzen Lisdexamfetamin (Vyvanse®) und SPD-465 beruhen auf dem Wirkprinzip der Stimulantien. Mehrere in verschiedenen Entwicklungsstadien befindliche Substanzen weisen verschiedene andere Wirkmechanismen auf: Guanfacine/SPD-503 wirkt agonistisch am α2A-Adrenozeptor, während ABT-089 und ABT-418 vor allem als Partialagonisten am α4β2-Subtyp des nikotinischen Acetylcholinrezeptors ihre Wirkung entfalten. CX-717, -1739, -1942 und -1796 sind Agonisten am glutamatergen αAmino-3-hydroxy-5-methyl-4-isoxazol-Propion-Acid (AMPA)-Rezeptor und PF-3654746 wirkt als Antagonist am histaminergen H 3-Rezeptor. Guanfacine (Intuniv®), ein α2A-Adrenozeptor-Agonist und Lisdexamfetamin (Vyvanse®), ein über die Leber aktiviertes „Pro-Drug“ eines Amphetamins sind mittlerweile in den USA zugelassen. Die vorliegende Übersichtsarbeit fasst bewertend die etablierten und insbesondere mögliche, zukünftige symptomatische pharmakologische Therapieoptionen von Stimulantien und Nicht-Stimulantien in der ADHS-Behandlung zusammen.

Abstract

The current pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) is mainly based on the stimulant methylphenidate and to a small extent on amphetamines which are not approved in Germany. The only approved non-stimulant so far is atomoxetin (Strattera®), a norepinephrine reuptake inhibitor. There is no approved pharmacotherapy for adults. The aim of the available medication is a reduction of impulsivity, hyperactivity, and attention deficits. Neurobiological correlates of these effects are still not fully understood, however, a functional implication of dopaminergic and noradrenergic systems is known. To date there is no disease-modifying therapy. The currently available substances have limitations due to the short half-life of stimulants, the unknown pathomechanisms, and the use of stimulants in developing brains with possible long-term side-effects. Moreover, the abuse potential of stimulants is still controversially discussed. The recently developed Lisdexamfetamin and SPD-465 have stimulant effects, too. A number of different developmental substances in preclinical and clinical phases show other mechanisms: SPD-503 represents an α2A-adrenozeptoragonist, ABT-089 and ABT-418 have partial agonistic effects to the α4β2-subtype of nicotinic acetylcholinreceptors, CX-717, -1739, -1942 and -1796 are glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor agonists and PF-3 654 746 exhibits antagonistic properties to histaminergic H 3-receptors. The α2A-adrenoceptor-agonist Guanfacine (Intuniv®) and the hepatic metabolised amphetamine prodrug Lisdexamfetamin (Vyvanse®) are yet approved for ADHD treatment in the USA. The aim of this review is to summarise established pharmacological treatment options and the stage of development of upcoming symptomatic stimulant and non-stimulant substances in ADHD therapy.

Schlüsselwörter

ADHS - Therapie - Pharmaka - Stimulantien - Neuentwicklungen

Keywords

ADHD - therapy - drugs - stimulants - developments

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Dr. Dr. Andreas Günter Franke, M.A.

Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin Mainz

Untere Zahlbacher Str. 8

55131 Mainz

Email: afranke@uni-mainz.de

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