How antipsychotics impact the different dimensions of Schizophrenia: A test of competing hypotheses

Tiago Reis Marques, Stephen Z. Levine, Avi Reichenberg, Rene Kahn, Eske M. Derks, Wolfgang W. Fleischhacker, Jonathan Rabinowitz, Shitij Kapur

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)1279-1288
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume24
Issue number8
DOIs
StatePublished - Aug 2014

Bibliographical note

Funding Information:
Data used in the preparation of this article were obtained from the limited access datasets (version 1.7) distributed from the NIH -supported “Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia” (CATIE-Sz). This is a multisite clinical trial of persons with schizophrenia comparing the effectiveness of randomly assigned medication treatment. The study was supported by NIMH Contract #N01MH90001 to the University of North Carolina at Chapel Hill. The Clinical Trials.gov identifier is NCT00014001 . This presentation reflects the views of the authors and may not reflect the opinions or views of the CATIE-Sz Study Investigators or the NIH.

Funding

Data used in the preparation of this article were obtained from the limited access datasets (version 1.7) distributed from the NIH -supported “Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia” (CATIE-Sz). This is a multisite clinical trial of persons with schizophrenia comparing the effectiveness of randomly assigned medication treatment. The study was supported by NIMH Contract #N01MH90001 to the University of North Carolina at Chapel Hill. The Clinical Trials.gov identifier is NCT00014001 . This presentation reflects the views of the authors and may not reflect the opinions or views of the CATIE-Sz Study Investigators or the NIH.

FundersFunder number
National Institute of Mental HealthN01MH090001
Medical Research CouncilG0701748

    Keywords

    • Antipsychotic response
    • Antipsychotics
    • Factor analysis
    • Schizophrenia
    • Symptom dimensions

    Fingerprint

    Dive into the research topics of 'How antipsychotics impact the different dimensions of Schizophrenia: A test of competing hypotheses'. Together they form a unique fingerprint.

    Cite this