Stefan Leucht1, Inge Winter-van Rossum2, Stephan Heres3, Celso Arango4, W Wolfgang Fleischhacker5, Birte Glenthøj6, Marion Leboyer7, F Markus Leweke8, Shôn Lewis9, Phillip McGuire10, Andreas Meyer-Lindenberg8, Dan Rujescu11, Shitij Kapur10, René S Kahn2, Iris E Sommer2. 1. Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, München, Germany; Stefan.Leucht@lrz.tum.de. 2. Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands; 3. Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, München, Germany; 4. Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain; 5. Biological Psychiatry Division, Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria; 6. Center for Neuropsychiatric Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Psychiatric Hospital Center Glostrup, Glostrup, Denmark; 7. INSERM U955, Translational Psychiatry Team, Créteil, France, Paris Est University, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France, Fondation FondaMental; 8. Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; 9. University of Manchester, Manchester, UK; 10. Department of Psychological Medicine, King's College London, Institute of Psychiatry, London, UK; 11. Department of Psychiatry, Psychotherapy and Psychosomatics Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Abstract
BACKGROUND: Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia. METHODS: We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial. RESULTS: We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence. DISCUSSION: Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia.
BACKGROUND: Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia. METHODS: We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial. RESULTS: We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence. DISCUSSION: Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia.
Authors: Robert A Rosenheck; Sonia Davis; Nancy Covell; Susan Essock; Marvin Swartz; Scott Stroup; Joseph McEvoy; Jeffrey Lieberman Journal: Schizophr Res Date: 2008-11-06 Impact factor: 4.939
Authors: Bruce J Kinon; Lei Chen; Haya Ascher-Svanum; Virginia L Stauffer; Sara Kollack-Walker; Wei Zhou; Shitij Kapur; John M Kane Journal: Neuropsychopharmacology Date: 2010-01 Impact factor: 7.853
Authors: David M Gardner; Andrea L Murphy; Heather O'Donnell; Franca Centorrino; Ross J Baldessarini Journal: Am J Psychiatry Date: 2010-04-01 Impact factor: 18.112
Authors: Oliver D Howes; Francis Vergunst; Siobhan Gee; Philip McGuire; Shitij Kapur; David Taylor Journal: Br J Psychiatry Date: 2012-09-06 Impact factor: 9.319
Authors: G Fond; O Godin; L Boyer; F Berna; M Andrianarisoa; N Coulon; L Brunel; E Bulzacka; B Aouizerate; D Capdevielle; I Chereau; T D'Amato; C Dubertret; J Dubreucq; C Faget; S Leignier; C Lançon; J Mallet; D Misdrahi; C Passerieux; R Rey; A Schandrin; M Urbach; P Vidailhet; P M Llorca; F Schürhoff; M Leboyer Journal: Eur Arch Psychiatry Clin Neurosci Date: 2018-05-28 Impact factor: 5.270
Authors: Amedeo Minichino; Morwenna Senior; Natascia Brondino; Sam H Zhang; Beata R Godwlewska; Philip W J Burnet; Andrea Cipriani; Belinda R Lennox Journal: JAMA Psychiatry Date: 2019-09-01 Impact factor: 21.596
Authors: Sameer Jauhar; Matthew M Nour; Mattia Veronese; Maria Rogdaki; Ilaria Bonoldi; Matilda Azis; Federico Turkheimer; Philip McGuire; Allan H Young; Oliver D Howes Journal: JAMA Psychiatry Date: 2017-12-01 Impact factor: 21.596
Authors: Jessica de Nijs; Thijs J Burger; Ronald J Janssen; Seyed Mostafa Kia; Daniël P J van Opstal; Mariken B de Koning; Lieuwe de Haan; Wiepke Cahn; Hugo G Schnack Journal: NPJ Schizophr Date: 2021-07-02