title: The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial: rationale for its methodology and a review of the effectiveness of switching antipsychotics.
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.
  
  
  CONCLUSIONS
  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: Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, München, Germany; Stefan.Leucht@lrz.tum.de.
authors: Stefan
authors: S
authors: Leucht
authors: Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors: Inge
authors: I
authors: Winter-van Rossum
authors: Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, München, Germany;
authors: Stephan
authors: S
authors: Heres
authors: Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain;
authors: Celso
authors: C
authors: Arango
authors: Biological Psychiatry Division, Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria;
authors: W Wolfgang
authors: WW
authors: Fleischhacker
authors: Center for Neuropsychiatric Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Psychiatric Hospital Center Glostrup, Glostrup, Denmark;
authors: Birte
authors: B
authors: Glenthøj
authors: 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;
authors: Marion
authors: M
authors: Leboyer
authors: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;
authors: F Markus
authors: FM
authors: Leweke
authors: University of Manchester, Manchester, UK;
authors: Shôn
authors: S
authors: Lewis
authors: Department of Psychological Medicine, King's College London, Institute of Psychiatry, London, UK;
authors: Phillip
authors: P
authors: McGuire
authors: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;
authors: Andreas
authors: A
authors: Meyer-Lindenberg
authors: Department of Psychiatry, Psychotherapy and Psychosomatics Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors: Dan
authors: D
authors: Rujescu
authors: Department of Psychological Medicine, King's College London, Institute of Psychiatry, London, UK;
authors: Shitij
authors: S
authors: Kapur
authors: Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors: René S
authors: RS
authors: Kahn
authors: Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors: Iris E
authors: IE
authors: Sommer
mesh_terms: D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D017326:Clinical Trials, Phase III as Topic; D019468:Disease Management; D005060:Europe; D006801:Humans; D015337:Multicenter Studies as Topic; D000077152:Olanzapine; D017063:Outcome Assessment, Health Care; D011618:Psychotic Disorders / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D013469:Sulpiride / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; D000077152:Olanzapine
keywords: algorithm; amisulpride; first episode; nonresponse; olanzapine; schizophrenia