title: How antipsychotics impact the different dimensions of Schizophrenia: a test of competing hypotheses.
abstract: The clinical expression of schizophrenia is generally reported to be expressed by three to five different factors (i.e. positive, negative, disorganization, excitability, anxiety-depression symptoms). It is often claimed that antipsychotic medications are particularly helpful for positive symptoms, but not for the others, suggesting a differential efficacy for different aspects of the disorder. We formally tested this claim. Using Structural Equation Modeling in two large [1884 patients] clinical trials in schizophrenia, we compared the model of a common general effect of antipsychotics to models whereby the antipsychotics have multiple and differential effects on the different factors of the illness. We validated the generalizability of the model in further trials involving antipsychotics in chronic [1460 patients] and first-episode patients [1053 patients]. Across different populations, different trials and different antipsychotics - the best-fitting model suggests that symptom response in schizophrenia is underpinned by a single general effect with secondary and minor lower-order effects on specific symptom domains. This single-factor model explained nearly 80% of the variance, was superior to the assumption of unique efficacy for specific domains; and replicated across antipsychotics and illness stages. Despite theoretical and pharmacological claims the differential efficacy of antipsychotics on the various dimensions of schizophrenia is not supported in the prevailing data. The implication of this finding for the measurement of treatment response and our understanding of the neurobiology of antipsychotic action, for clinical practice and for future drug development are discussed.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King׳s College London, PO Box 053, London SE5 8AF, UK. Electronic address: reismarques@gmail.com.
authors.forename: Tiago Reis
authors.initials: TR
authors.lastname: Marques
authors.affiliation: Department of Community Mental Health, University of Haifa, Israel.
authors.forename: Stephen Z
authors.initials: SZ
authors.lastname: Levine
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King׳s College London, PO Box 053, London SE5 8AF, UK; Departments of Psychiatry and Preventive Medicine, Icahn Medical School, Mount Sinai, NY, USA.
authors.forename: Avi
authors.initials: A
authors.lastname: Reichenberg
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Kahn
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eske M
authors.initials: EM
authors.lastname: Derks
authors.affiliation: Department of Biological Psychiatry, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Fleischhacker
authors.affiliation: Bar Ilan University, Ramat Gan, Israel.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rabinowitz
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King׳s College London, PO Box 053, London SE5 8AF, UK. Electronic address: shitij.kapur@kcl.ac.uk.
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000704:Analysis of Variance; D000850:Anomie; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology*; D002986:Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy / Q000209:etiology*; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic response; Antipsychotics; Factor analysis; Schizophrenia; Symptom dimensions