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Neuentwicklungen in der Pharmakotherapie der Depression

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Zusammenfassung

Trotz aller Fortschritte in den letzten Jahren stellt die Pharmakotherapie der Depression immer noch eine beträchtliche Herausforderung für den Psychiater dar. Ein besonderes Problem ist die Latenz bis zum Eintreten der antidepressiven Wirkung von bis zu mehreren Wochen bei allen bislang auf dem Markt befindlichen Präparaten. Die Non-Response-Quote für Antidepressiva liegt bei ca. 30%, ferner weisen die verfügbaren Antidepressiva ein charakteristisches Nebenwirkungsspektrum auf. Die gängigen pharmakologischen antidepressiven Therapieansätze zielen auf eine Verbesserung der serotonergen bzw. noradrenergen Neurotransmission ab. Mittlerweile gibt es jedoch auch völlig neuartige pharmakologische Interventionsstrategien. Plazebokontrollierte Doppelblindstudien, welche für eine mögliche antidepressive Wirkung dieser Substanzen sprechen, wurden mit 5-HT1A-Rezeptor-Agonisten und Tachykininrezeptorantagonisten durchgeführt. Wenn sich auch in tierexperimentellen Untersuchungen, Kasuistiken, offenen sowie plazebokontrollierten Studien mit relativ kleiner Fallzahl erste Hinweise für eine antidepressive Wirksamkeit durch Intervention an verschiedenen Angriffsorten innerhalb des Hypothalamus-Hypophysen-Nebennierenrinden-Systems, wie z. B. durch CRH1-Rezeptor-Antagonisten, Steroidsynthesehemmer und Glukokortikoidrezeptorantagonisten, finden lassen, wurde bislang ein hinreichender Nachweis für deren klinische Wirksamkeit, wie sie für die Prüfung von Antidepressiva gefordert werden, noch nicht erbracht. Die dargestellten neuartigen Therapieprinzipien in der Depressionsbehandlung sollten jedoch unbedingt weiterverfolgt werden, um die Behandelbarkeit von Depressionen, auch aufgrund deren großer gesundheitspolitischer Relevanz, weiter zu verbessern.

Summary

In spite of recent progress in the pharmacotherapy of depression, major issues are still unresolved. These include the nonresponse rate of approximately 30% to conventional antidepressant pharmacotherapy, side effects of available antidepressants, and the latency period of several weeks until clinical improvement. Current treatment strategies aim to enhance serotonergic and/or noradrenergic neurotransmission. However, in the meantime, several new pharmacological principles are under investigation with regard to their antidepressant potency. Placebo-controlled, double-blind studies have been performed with 5-HT1A receptor agonists and tachykinin receptor antagonists which point towards antidepressant efficacy. While there is some evidence for putative antidepressant properties of various interventions within the hypothalamic-pituitary-adrenal system such as CRH1 receptor antagonists, steroid synthesis inhibitors, and glucocorticoid receptor antagonists in animal studies, case series, open studies, and small placebo-controlled studies, no definite proof for their antidepressant efficacy has been furnished. Nevertheless, follow-up of new pharmacological strategies is of major importance to provide even better strategies for the clinical management of depression, which also has great socioeconomic impact.

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Authors and Affiliations

  1. Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität München

    R. Rupprecht, Th. C. Baghai & H.-J. Möller

  2. Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität, Nußbaumstraße 7, 80336 , München

    R. Rupprecht

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Correspondence to R. Rupprecht.

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Rupprecht, R., Baghai, T.C. & Möller, HJ. Neuentwicklungen in der Pharmakotherapie der Depression. Nervenarzt 75, 273–280 (2004). https://doi.org/10.1007/s00115-003-1517-2

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