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Fortschr Neurol Psychiatr 2001; 69(12): 592-596
DOI: 10.1055/s-2001-19179
Übersicht
Georg Thieme Verlag Stuttgart · New York

Zolpidem: Zur Entwicklung von Toleranz und Abhängigkeit anhand von Fallberichten, systematischen Studien und aktuellen molekularbiologischen Daten

Zolpidem: The Risk of Tolerance and Dependence According to Case Reports, Systematic Studies and Recent Molecularbiological DataR.  Göder1 , V.  Treskov1 , J.  Burmester2 , J.  B.  Aldenhoff1 , D.  Hinze-Selch1
  • 1Klinik für Psychiatrie und Psychotherapie der Christian-Albrechts-Universität zu Kiel (Direktor: Prof. Dr. J. B. Aldenhoff)
  • 2Praxis für Psychiatrie und Psychotherapie, Kiel
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Publication History

Publication Date:
19 December 2001 (online)

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Zusammenfassung

Wir sowie etwa 20 weitere Veröffentlichungen berichten von Fällen der Toleranzentwicklung und Abhängigkeit von Zolpidem. Epidemiologische und polysomnographische Studien weisen auf ein für Zolpidem vorhandenes, im Vergleich zu Benzodiazepinen jedoch niedrigeres Abhängigkeitsrisiko hin. Neuere molekularbiologische Erkenntnisse könnten dafür begründend sein. Denn Zolpidem hat im Vergleich zu Benzodiazepinen in empfohlener Dosis eine fast ausschließliche Affinität für die mit Schlafförderung assoziierte α1-Untereinheit des GABAA-Rezeptors und in höheren Dosen eine zusätzliche niedrigere Affinität für die mit Anxiolyse assoziierten α-Untereinheiten 2, 3 und 5. Da in experimentellen Studien auch Alter, Geschlecht und Alkoholkonsum einen Einfluss haben auf die Expression der Rezeptoruntereinheiten in einzelnen Hirnregionen, erscheinen neben der Dosierung und Dauer der Anwendung auch diese Faktoren relevant zur Einschätzung des Abhängigkeitsrisikos einzelner Patienten.

Abstract

Our group as well as about 20 other publications report cases of dependence from zolpidem. Furthermore, there is epidemiological and polysomnographic evidence that there is a risk for tolerance and dependence for zolpidem although lower than in the case of benzodiazepines. Recent molecularbiological findings offer interesting data in this respect. Whereas in the recommended dose range zolpidem almost exclusively binds to the α1 subunit of the GABAA receptor associated with sleep promotion, in higher doses it also binds the α2, α3 and α5 subunits typically targeted by benzodiazepines and associated with anxiolytic effects. Moreover, because age, gender and alcohol were shown to significantly affect expression of these subunits in individual brain regions, dosage and duration of treatment with zolpidem as well as age, gender and additional consumption of alcohol, a history of abuse and dependence might play a role in the development of tolerance and dependence in individual patients.

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Dr. R. Göder

Klinik für Psychiatrie und Psychotherapie

Niemannsweg 147

24105 Kiel

Email: rgoeder@psychiatry.uni-kiel.de