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Therapie kognitiver Defizite durch AChE-Hemmer bei Patienten mit Schizophrenie

Eine systematische Übersicht

Therapy of cognitive deficits in schizophrenia with acetylcholinesterase inhibitors

A systematic overview

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Zusammenfassung

Neben der psychopathologischen Symptomatik treten bei Patienten mit Schizophrenie kognitive Defizite auf, die den Krankheitsverlauf und die soziale Integration wesentlich beeinflussen. Veränderungen im cholinergen System, wie eine reduzierte Anzahl muskarinerger und nikotinerger Rezeptoren, werden mit diesen kognitiven Defiziten in Verbindung gebracht. Da sich langfristig kognitive Einschränkungen durch eine Behandlung mit antipsychotischen Medikamenten nicht wesentlich bessern, wurde versucht, durch pharmakologische Intervention im cholinergen System mittels Acetylcholinesterasehemmern diese Defizite anzugehen. In dieser Übersicht werden Grundlagen kognitiver Defizite bei Schizophrenie sowie Studienergebnisse zur pharmakologischen Beeinflussung durch verschiedene Acetylcholinesterasehemmer (Donepezil, Rivastigmin, Physostigmin, Galantamin) vorgestellt. Bislang existierende randomisierte, plazebokontrollierte Studien zu Donepezil und Rivastigmin konnten positive Ergebnisse vorangegangener unkontrollierter Studien nicht bestätigen. Besonders bezogen auf Substanzen mit spezifischeren Wirkmechanismen (z. B. Galantamin) besteht weiterhin ein großer Forschungsbedarf.

Summary

Patients with schizophrenia suffer from cognitive deficits which are important predictors of functional outcome. Alterations such as reduced muscarinic and nicotinic receptors in the central cholinergic system in patients with schizophrenia may contribute to these cognitive impairments. Because such deficits do not respond to neuroleptic treatment, different approaches have been developed regarding pharmacological treatments that enhance central cholinergic transmission, e.g. with acetylcholinesterase inhibitors. In this review the pathophysiology of cognitive impairment in schizophrenia, results of studies using acetylcholinesterase inhibitors (donepezil, rivastigmine, physostigmine, and galantamine), and future research strategies are presented. Till now randomized, placebo-controlled studies exist only for donepezil and rivastigmine, and none could replicate the positive results of previous trials with open designs. More trials with higher numbers of patients are needed, particularly for substances with more complex mechanisms of action (e.g. galantamine).

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Wir danken Herrn Dr. I. Vernaleken herzlich für die hilfreichen Kommentare zu früheren Versionen des Manuskriptes.

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  1. Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Aachen, RWTH, Pauwelsstraße 30, 52074, Aachen, Deutschland

    B. Voß, R. Thienel &  T. Kircher

  2. Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, München, Deutschland

    S. Leucht

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  1. B. Voß
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Voß, B., Thienel, R., Leucht, S. et al. Therapie kognitiver Defizite durch AChE-Hemmer bei Patienten mit Schizophrenie. Nervenarzt 79, 47–59 (2008). https://doi.org/10.1007/s00115-007-2358-1

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