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Original Research

Impact of Second-Generation Antipsychotics and Perphenazine on Depressive Symptoms in a Randomized Trial of Treatment for Chronic Schizophrenia

Donald E. Addington, MD; Somaia Mohamed, MD, PhD; Robert A. Rosenheck, MD; Sonia M. Davis, PhD; Thomas Scott Stroup, MD, MPH; Joseph P. McEvoy, MD; Marvin S. Swartz, MD; and Jeffrey A. Lieberman, MD

Published: September 21, 2010

Article Abstract

Background: According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004.

Method: Patients with DSM-IV-defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of 6, indicative of a current major depressive episode (MDE).

Results: There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056).

Conclusions: We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for the clinical practice recommendation, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.

Trial Registration: Identifier: NCT00014001

J Clin Psychiatry

Submitted: March 31, 2009; accepted July 21, 2009.

Online ahead of print: September 21, 2010 (doi:10.4088/JCP.09m05258gre).

Corresponding author: Donald E. Addington, MD, Department of Psychiatry, Foothills Hospital, 1403 29th St NW, Calgary, Alberta, Canada T2N 2T9 (

Volume: 71

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