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Pharmakotherapie der Schizophrenie

Pharmacotherapy of schizophrenia

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Zusammenfassung

Hintergrund

Schizophrenie ist eine schwere psychische Erkrankung mit variablem therapeutischem Ansprechen. Ätiologie und Pathophysiologie bedürfen der weiteren Klärung.

Fragestellung

Welche pharmakologischen Optionen sind für welche Therapieziele bei Patienten mit einer Schizophrenie wirksam und sicher?

Material und Methoden

Narratives Review der pharmakologischen Therapie bei Erwachsenen mit einer Schizophrenie.

Ergebnisse

Trotz heterogenen therapeutischen Ansprechens sind derzeit nur Dopaminblocker/-partialagonisten für die Schizophrenietherapie zugelassen. Die Wirksamkeit von Antipsychotika unterscheidet sich graduell, mit Ausnahme von Clozapin bei therapieresistenter Schizophrenie, wohingegen unerwünschte Arzneimittelwirkungen (UAW) weit variabler sind. Antipsychotika, die in Metaanalysen der Akut- und Erhaltungstherapie graduelle Effektivitätsvorteile zeigen (Clozapin, Amisulprid, Olanzapin, Risperidon), haben mindestens eine UAW, die am ausgeprägtesten ist. Antipsychotische UAW betreffen Subgruppen von Patienten und sind zumeist tolerierbar/behandelbar, wohingegen die „Nebenwirkung“ der unbehandelten Schizophrenie fast alle Patienten betrifft, inklusive Rückfälle, psychosoziale Verschlechterung, sekundäre Therapieresistenz und erhöhte Mortalität. Darum ist bei gesicherter Schizophreniediagnose wahrscheinlich derzeit eine lebenslange kontinuierliche Therapie indiziert, idealerweise mit Antipsychotika, bei denen Adhärenz direkt messbar und verbessert ist. Bei Therapieresistenz ist Clozapin Mittel der Wahl, gefolgt von der Elektrokrampftherapie, die auch die beste Augmentationsevidenz bei Clozapin-Resistenz hat.

Diskussion

Neue Therapeutika mit verbesserter Effektivität und Tolerabilität sowie Wirksamkeit für Negativsymptomatik und Kognition sind erforderlich.

Abstract

Background

Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation.

Objective

To review which pharmacological options are effective and safe and for which treatment goals in schizophrenia.

Material and methods

Narrative review of the pharmacological therapy of adults diagnosed with schizophrenia.

Results

Despite heterogeneous therapeutic responses, to date only dopamine antagonists or partial agonists are approved for the treatment of schizophrenia. The efficacy of antipsychotic agents differs only gradually, with the exception of clozapine for treatment-resistant schizophrenia, whereas undesired adverse effects are more variable. Those antipsychotic agents that show gradual efficacy advantages in meta-analyses of acute and maintenance treatment (clozapine, amisulpride, olanzapine, risperidone) are also those where at least one undesired adverse effect is most severely expressed. Antipsychotic adverse effects occur in subgroups of patients and are generally tolerable or treatable, whereas the “side effect” of untreated schizophrenia affects almost all patients, including relapses, psychosocial deterioration, secondary treatment resistance and increased mortality. Therefore, in patients with a confirmed diagnosis of schizophrenia, a lifelong continuous therapy is currently most likely indicated, ideally with antipsychotic agents for which adherence is directly measurable and improved. In the case of treatment resistant clozapine is the agent of choice, followed by electroconvulsive therapy, which also has the best evidence as augmentation treatment in cases of clozapine resistance.

Conclusion

New therapeutic agents with improved efficacy and tolerability as well as effectiveness for negative symptoms and cognitive disturbance are needed.

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Author information

Correspondence to Prof. Dr. C. U. Correll.

Ethics declarations

Interessenkonflikt

C.U. Correll war in den letzten 3 Jahren entweder Berater für und/oder hat Honorare von den folgenden Firmen erhalten: Alkermes, Allergan, Angelini, Gedeon Richter, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda und Teva. Er hat als Experte vor Gericht für folgende Firmen ausgesagt: Janssen und Otsuka. Er war Teil des Datensicherheitskommittees von Studien von Lundbeck, Rovi, Supernus und Teva. Er hat Forschungsmittel von Janssen und Takeda erhalten und hat Stock Options für LB Pharma.

Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Correll, C.U. Pharmakotherapie der Schizophrenie. Nervenarzt 91, 34–42 (2020) doi:10.1007/s00115-019-00858-z

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Schlüsselwörter

  • Negativsymptomatik
  • Kognition
  • Antipsychotika
  • Wirksamkeit
  • Nebenwirkungen

Keywords

  • Negative symptoms
  • Cognition
  • Antipsychotic agents
  • Efficacy
  • Side effects