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.
Literatur
Kahn RS, Sommer IE, Murray RM et al (2005) Schizophrenia. Nat Rev Dis Primers 2015(12):15067
Krogmann A, Peters L, von Hardenberg L, Bödeker K, Nöhles VB, Correll CU (2019) Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. CNS Spectr 24:38–69
Krynicki CR, Upthegrove R, Deakin JFW, Barnes TRE (2018) The relationship between negative symptoms and depression in schizophrenia: a systematic review. Acta Psychiatr Scand 137:380–390
Huhn M, Nikolakopoulou A, Schneider-Thoma J et al (2019) Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet 394:939–951
Carbon M, Correll CU (2014) Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 19(Suppl 1):35–53
Carbon M, Correll CU (2014) Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci 16:505–524
Correll CU, Galling B, Pawar A et al (2018) Comparison of early intervention services vs treatment as usual for early-phase psychosis: a systematic review, meta-analysis, and meta-regression. Jama Psychiatry 75:555–565
Zhu Y, Li C, Huhn M et al (2017) How well do patients with a first episode of schizophrenia respond to antipsychotics: a systematic review and meta-analysis. Eur Neuropsychopharmacol 27:835–844
Leucht S, Leucht C, Huhn M et al (2017) Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry 174:927–942
Zhang JP, Gallego J, Robinson D et al (2013) Efficacy and safety of individual second-generation vs first-generation antipsychotics in first episode schizophrenia: a systematic review and meta-analysis. Int J Neuropsychopharmacol 16:1205–1218
Correll CU, Rubio JM, Kane JM (2018) What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry 17:149–160
Tiihonen J, Tanskanen A, Taipale H (2018) 20-year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. Am J Psychiatry 175:765–773
Leucht S, Tardy M, Komossa K et al (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 379:2063–2071
Kishimoto T, Agarwal V, Kishi T et al (2013) Maintenance treatment and relapse prevention in schizophrenia: systematic review and meta-analysis of randomized controlled trials of first-generation and second-generation antipsychotics. Mol Psychiatry 18:53–66
Kishimoto T, Hagi K, Nitta M, Kane JM, Correll CU (2019) Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons. World Psychiatry 18:208–224
Krause M, Zhu Y, Huhn M et al (2018) Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci 268:625–639
Correll CU, Rubio JM, Inczedy-Farkas G (2017) Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence. Jama Psychiatry 74:675–684
Howes OD, McCutcheon R, Agid O et al (2017) Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on diagnosis and terminology. Am J Psychiatry 174:216–229
Samara MT, Dold M, Gianatsi M et al (2016) Efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia: a network meta-analysis. Jama Psychiatry 73:199–210
Masuda T, Misawa F, Takase M, Kane JM, Correll CU (2019) Association with hospitalization and all-cause discontinuation among patients with schizophrenia on clozapine vs other oral second-generation antipsychotics: a systematic review and meta-analysis of cohort studies. Jama Psychiatry 76:1052–1062
Okhuijsen-Pfeifer C, Huijsman EAH, Hasan A (2018) Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis. Acta Psychiatr Scand 138:281–288
Solmi M, Murru A, Pacchiarotti I et al (2017) Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag 13:757–777
Galling B, Roldán A, Hagi K et al (2017) Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry 16:77–89
Tiihonen J, Taipale H, Mehtälä J et al (2019) Association of antipsychotic polypharmacy vs monotherapy with psychiatric rehospitalization among adults with schizophrenia. Jama Psychiatry 76:499–507
Wang G, Zheng W, Li XB et al (2018) ECT augmentation of clozapine for clozapine-resistant schizophrenia: a meta-analysis of randomized controlled trials. J Psychiatr Res 105:23–32
Correll CU, Citrome L, Haddad PM et al (2016) The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry 77(Suppl 3):1–24
Firth J, Siddiqi N, Koyanagi A et al (2019) The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness. The Lancet Psychiatry 6:675–712
Papola D, Ostuzzi G, Gastaldon C et al (2019) Antipsychotic use and risk of life-threatening medical events: umbrella review of observational studies. Acta Psychiatr Scand 140:227–243
Vancampfort D, Firth J, Correll CU et al (2019) The impact of pharmacological and non-pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry 18:53–66
Solmi M, Pigato G, Kane JM, Correll CU (2018) Treatment of tardive dyskinesia with VMAT‑2 inhibitors: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther 12:1215–1238
Author information
Authors and Affiliations
Corresponding author
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.
Rights and permissions
About this article
Cite this article
Correll, C.U. Pharmakotherapie der Schizophrenie. Nervenarzt 91, 34–42 (2020). https://doi.org/10.1007/s00115-019-00858-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00115-019-00858-z