Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial

Richard S.E. Keefe, Robert M. Bilder, Sonia M. Davis, Philip D. Harvey, Barton W. Palmer, James M. Gold, Herbert Y. Meltzer, Michael F. Green, George Capuano, T. Scott Stroup, Joseph Patrick McEvoy, Marvin S. Swartz, Robert A. Rosenheck, Diana O. Perkins, Clarence E. Davis, John K. Hsiao, Jeffrey A. Lieberman

Research output: Contribution to journalArticle

737 Citations (Scopus)

Abstract

Context: Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined. Objective: To compare the neurocognitive effects of several second-generation antipsychotics and a firstgeneration antipsychotic, perphenazine. Design: Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration. Setting: Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community. Patients: From a cohort of 1460 patients in the treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment. Main Outcome Measures: The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Results: At 2 months, treatment resulted in small neurocognitive improvements of z=0.13 for olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. Conclusions: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.

Original languageEnglish (US)
Pages (from-to)633-647
Number of pages15
JournalArchives of General Psychiatry
Volume64
Issue number6
DOIs
StatePublished - Jun 1 2007

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Antipsychotic Agents
Schizophrenia
Perphenazine
olanzapine
Risperidone
Therapeutics
Medication
Cohort Effect
Health Facilities
United States Food and Drug Administration
Random Allocation
Double-Blind Method
Mental Health
Outcome Assessment (Health Care)
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

Keefe, R. S. E., Bilder, R. M., Davis, S. M., Harvey, P. D., Palmer, B. W., Gold, J. M., ... Lieberman, J. A. (2007). Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Archives of General Psychiatry, 64(6), 633-647. https://doi.org/10.1001/archpsyc.64.6.633

Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. / Keefe, Richard S.E.; Bilder, Robert M.; Davis, Sonia M.; Harvey, Philip D.; Palmer, Barton W.; Gold, James M.; Meltzer, Herbert Y.; Green, Michael F.; Capuano, George; Stroup, T. Scott; McEvoy, Joseph Patrick; Swartz, Marvin S.; Rosenheck, Robert A.; Perkins, Diana O.; Davis, Clarence E.; Hsiao, John K.; Lieberman, Jeffrey A.

In: Archives of General Psychiatry, Vol. 64, No. 6, 01.06.2007, p. 633-647.

Research output: Contribution to journalArticle

Keefe, RSE, Bilder, RM, Davis, SM, Harvey, PD, Palmer, BW, Gold, JM, Meltzer, HY, Green, MF, Capuano, G, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, Davis, CE, Hsiao, JK & Lieberman, JA 2007, 'Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial', Archives of General Psychiatry, vol. 64, no. 6, pp. 633-647. https://doi.org/10.1001/archpsyc.64.6.633
Keefe, Richard S.E. ; Bilder, Robert M. ; Davis, Sonia M. ; Harvey, Philip D. ; Palmer, Barton W. ; Gold, James M. ; Meltzer, Herbert Y. ; Green, Michael F. ; Capuano, George ; Stroup, T. Scott ; McEvoy, Joseph Patrick ; Swartz, Marvin S. ; Rosenheck, Robert A. ; Perkins, Diana O. ; Davis, Clarence E. ; Hsiao, John K. ; Lieberman, Jeffrey A. / Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. In: Archives of General Psychiatry. 2007 ; Vol. 64, No. 6. pp. 633-647.
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AU - Palmer, Barton W.

AU - Gold, James M.

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N2 - Context: Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined. Objective: To compare the neurocognitive effects of several second-generation antipsychotics and a firstgeneration antipsychotic, perphenazine. Design: Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration. Setting: Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community. Patients: From a cohort of 1460 patients in the treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment. Main Outcome Measures: The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Results: At 2 months, treatment resulted in small neurocognitive improvements of z=0.13 for olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. Conclusions: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.

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