title: Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: analysis of the CATIE phase 2E data.
abstract: BACKGROUND
  The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E.
  
  
  METHODS
  Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models.
  
  
  RESULTS
  No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone.
  
  
  CONCLUSIONS
  The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE.
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. Electronic address: shinichiro_nakajima@hotmail.com.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan; Schizophrenia Division/Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: hirotak@dk9.so-net.ne.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada; Schizophrenia Division/Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: gagan.fervaha@camh.ca.
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: plitmaneric@gmail.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: junku.chung@mail.utoronto.ca.
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: fernando.caravaggio@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. Electronic address: yusuke.iwata2010@gmail.com.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: yukiko.mihashi@mail.utoronto.ca.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Mihashi
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: philgerretsen@yahoo.com.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan; Schizophrenia Division/Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Canada; Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: gary.remington@camh.ca.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: benoit.mulsant@camh.ca.
authors.forename: Benoit
authors.initials: B
authors.lastname: Mulsant
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: ariel_graff@yahoo.com.mx.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D002908:Chronic Disease; D003024:Clozapine / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate / Q000627:therapeutic use; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine
keywords: CATIE; Clozapine; Depression; Quetiapine; Schizophrenia