Shinichiro Nakajima1, Hiroyoshi Takeuchi2, Gagan Fervaha3, Eric Plitman4, Jun Ku Chung5, Fernando Caravaggio6, Yusuke Iwata7, Yukiko Mihashi8, Philip Gerretsen9, Gary Remington10, Benoit Mulsant11, Ariel Graff-Guerrero12. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: yukiko.mihashi@mail.utoronto.ca. 9. 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. 10. 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. 11. 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. 12. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Jeffrey A Lieberman; T Scott Stroup; Joseph P McEvoy; Marvin S Swartz; Robert A Rosenheck; Diana O Perkins; Richard S E Keefe; Sonia M Davis; Clarence E Davis; Barry D Lebowitz; Joanne Severe; John K Hsiao Journal: N Engl J Med Date: 2005-09-19 Impact factor: 91.245
Authors: Donald E Addington; Somaia Mohamed; Robert A Rosenheck; Sonia M Davis; Thomas Scott Stroup; Joseph P McEvoy; Marvin S Swartz; Jeffrey A Lieberman Journal: J Clin Psychiatry Date: 2010-09-21 Impact factor: 4.384
Authors: Robert A Rosenheck; Douglas L Leslie; Jody Sindelar; Edward A Miller; Haiqun Lin; T Scott Stroup; Joseph McEvoy; Sonia M Davis; Richard S E Keefe; Marvin Swartz; Diana O Perkins; John K Hsiao; Jeffrey Lieberman Journal: Am J Psychiatry Date: 2006-12 Impact factor: 18.112
Authors: Stefan Leucht; Andrea Cipriani; Loukia Spineli; Dimitris Mavridis; Deniz Orey; Franziska Richter; Myrto Samara; Corrado Barbui; Rolf R Engel; John R Geddes; Werner Kissling; Marko Paul Stapf; Bettina Lässig; Georgia Salanti; John M Davis Journal: Lancet Date: 2013-06-27 Impact factor: 79.321
Authors: Joseph P McEvoy; Jeffrey A Lieberman; T Scott Stroup; Sonia M Davis; Herbert Y Meltzer; Robert A Rosenheck; Marvin S Swartz; Diana O Perkins; Richard S E Keefe; Clarence E Davis; Joanne Severe; John K Hsiao Journal: Am J Psychiatry Date: 2006-04 Impact factor: 19.242
Authors: Denise S Pinheiro; Rodrigo da S Santos; Rodrigo B de Brito; Aline Helena da S Cruz; Paulo C Ghedini; Angela A S Reis Journal: PLoS One Date: 2017-08-24 Impact factor: 3.240