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Abstract

Early and effective treatment in first-episode schizophrenia is associated with better outcomes. Evidence suggests that response is generally robust in a first antipsychotic trial, but a marked reduction in response rate is observed among patients for whom a second trial is warranted, and even further reductions are seen in subsequent trials. Clozapine, the treatment of choice in refractory schizophrenia, is routinely employed only as a third-line treatment, and it has been shown to markedly enhance the rate of response, even when compared with other atypical antipsychotics. This raises the question of whether clozapine would be more effectively positioned as a first-line treatment. Current evidence addressing this question does not support this position, although the limited data available and methodological issues preclude a firm conclusion. Practical issues related to clozapine use, in combination with the robust response reported for other agents when used as first-line treatment, certainly call into question the likelihood that clozapine would be chosen if it were an option at this stage. In contrast, the notable reduction in response rate to second-line treatments, coupled with clozapine’s substantial response rate in refractory schizophrenia and evidence indicating better outcomes with early, effective treatment, makes a compelling argument for research examining clinical and functional outcomes with clozapine positioned as a second-line treatment.

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Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 146 - 151
PubMed: 23377634

History

Received: 12 June 2012
Revision received: 17 July 2012
Accepted: 8 August 2012
Published online: 1 February 2013
Published in print: February 2013

Authors

Details

Gary Remington, M.D., Ph.D.
From the Department of Psychiatry, University of Toronto; the Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto; and the Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto.
Ofer Agid, M.D.
From the Department of Psychiatry, University of Toronto; the Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto; and the Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto.
George Foussias, M.D., M.Sc.
From the Department of Psychiatry, University of Toronto; the Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto; and the Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto.
Margaret Hahn, M.D., M.Sc.
From the Department of Psychiatry, University of Toronto; the Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto; and the Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto.
Naren Rao, M.B.B.S., M.D.
From the Department of Psychiatry, University of Toronto; the Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto; and the Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto.
Mark Sinyor, M.D.
From the Department of Psychiatry, University of Toronto; the Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto; and the Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto.

Notes

Address correspondence to Dr. Remington ([email protected]).

Competing Interests

Dr. Remington has received research support from the Canadian Diabetes Association, the Canadian Institutes of Health Research, Medicure, Neurocrine Biosciences, Novartis Canada, Research Hospital Fund–Canada Foundation for Innovation, and the Schizophrenia Society of Ontario and has served as a consultant or speaker for Novartis, Laboratorios Farmacéuticos Rovi, and Roche. Dr. Agid has received research support from Pfizer and Janssen-Ortho and has served on advisory boards or speakers bureaus for Janssen-Ortho, Eli Lilly (Canada and U.S.), Novartis, Sepracor, and Sunovion. Dr. Foussias has been involved in research sponsored by Medicure and Neurocrine Bioscience and has served as a consultant for Roche. Dr. Sinyor has received grant support from the Physicians’ Services Incorporated Foundation. Drs. Hahn and Rao report no financial relationships with commercial interests.

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