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Metabolische Nebenwirkungen von Antipsychotika der neuen Generation

Antipsychotic drug-induced changes in metabolism

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Summary

Antipsychotic medications are a mainstay in the treatment of schizophrenia and are widely used in other psychiatric conditions. New generation antipsychotic agents (NGAs) are increasingly replacing first generation antipsychotic agents (FGAs), mainly due to a decreased risk for extrapyramidal symptoms, better overall tolerability, as well as some efficacy advantages. However, some of these NGAs are associated with adverse metabolic effects such as substantial weight gain, the induction of insulin resistance and lipid disorders. Among these substances, clozapine and olanzapine induce the most significant weight gain, olanzapine mainly by increasing body fat and both of these antipsychotics have been associated with disturbances in glucose metabolism. Diabetes mellitus induced by treatment with some NGAs occurred in many cases within days to weeks after initiation of SGA therapy, in some cases hyperglycemia promptly resolved after discontinuation of the medication and several reports have documented recurrent hyperglycemia after a rechallenge with the same drug. One possible pathomechanism for hyperglycemia induced by these NGAs is the induction of insulin resistance via humoral and/or cellular pathways. Alternatively, NGA induced diabetes may occur because of weight gain or a change in body fat distribution with a shift to a predominantly visceral fat type or through a direct effect on insulin sensitive target tissues. In this article we like to review the metabolic side effects of NGA treatment, highlight recent advances in the pathogenesis of these metabolic complications and discuss potential treatments of these side effects.

Zusammenfassung

Antipsychotika der neuen Generation verdrängen vermehrt die klassischen Antipsychotika, vor allem wegen des geringeren Risikos Nebenwirkungen des extrapyramidalmotorischen Systems hervorzurufen und aufgrund einiger therapeutischer Vorteile. Die Verwendung der Antipsychotika der neuen Generation wird jedoch vermehrt mit starker Gewichtszunahme, der Induktion einer Insulinresistenz und eines atherogenen Lipidprofils assoziiert. Unter diesen Substanzen führen Clozapin und Olanzapin zur stärksten Gewichtszunahme, hauptsächlich über eine Vermehrung des Körperfettes, und zu Veränderungen der Glukosehomöostase. In den meisten Fällen trat ein Diabetes mellitus bereits innerhalb von Tagen bis Wochen nach Therapiebeginn mit diesen Antipsychotika auf, in den meisten Fällen waren die neu aufgetretenen Störungen der Glukosehomöostase nach Absetzen der Medikation reversibel und einige Berichte beschreiben ein erneutes Auftreten bei neuerlicher Behandlung mit derselben Medikation. Ein möglicher Pathomechanismus für die Entstehung einer Hyperglykämie unter Therapie mit Antipsychotika der neuen Generation stellt die Beeinträchtigung der Insulinwirkung über humorale und/oder zelluläre Mechanismen dar. Alternativ könnte ein durch Antipsychotika induzierter Diabetes mellitus sekundär durch eine Gewichtszunahme entstehen oder infolge einer Veränderung der Fettverteilung, insbesondere einer Vermehrung der viszeralen Fettdepots, oder durch eine direkte Wirkung an insulinsensitiven Geweben. In diesem Artikel geben wir einen Überblick über die metabolischen Nebenwirkungen unter der Therapie mit Antipsychotika der neuen Generation, versuchen den Pathomechanismus dieser Nebenwirkungen zu beleuchten und möchten mögliche zukünftige Therapieansätze darstellen und diskutieren.

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  1. Klinische Abteilung für Allgemeine Innere Medizin, Universitätsklinik für Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Austria

    Julia Engl, Alexander Tschoner, Markus Laimer, Josef R. Patsch & Christoph Ebenbichler

  2. Abteilung für Biologische Psychiatrie, Universitätsklinik für Psychiatrie, Medizinische Universität Innsbruck, Innsbruck, Austria

    Maria Rettenbacher & W. Wolfgang Fleischhacker

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  1. Julia Engl
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  2. Alexander Tschoner
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  3. Markus Laimer
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  5. W. Wolfgang Fleischhacker
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Engl, J., Tschoner, A., Laimer, M. et al. Metabolische Nebenwirkungen von Antipsychotika der neuen Generation. Wien Klin Wochenschr 118, 196–206 (2006). https://doi.org/10.1007/s00508-006-0584-3

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