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

Publication ,  Journal Article
Keefe, RSE; Bilder, RM; Davis, SM; Harvey, PD; Palmer, BW; Gold, JM; Meltzer, HY; Green, MF; Capuano, G; Stroup, TS; McEvoy, JP; Swartz, MS ...
Published in: Arch Gen Psychiatry
June 2007

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 first-generation 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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Published In

Arch Gen Psychiatry

DOI

ISSN

0003-990X

Publication Date

June 2007

Volume

64

Issue

6

Start / End Page

633 / 647

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thiazoles
  • Schizophrenic Psychology
  • Schizophrenia
  • Risperidone
  • Quetiapine Fumarate
  • Psychiatry
  • Piperazines
  • Perphenazine
  • Olanzapine
 

Citation

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Keefe, R. S. E., Bilder, R. M., Davis, S. M., Harvey, P. D., Palmer, B. W., Gold, J. M., … Neurocognitive Working Group. (2007). Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry, 64(6), 633–647. https://doi.org/10.1001/archpsyc.64.6.633
Keefe, Richard S. E., Robert M. Bilder, Sonia M. Davis, Philip D. Harvey, Barton W. Palmer, James M. Gold, Herbert Y. Meltzer, et al. “Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial.Arch Gen Psychiatry 64, no. 6 (June 2007): 633–47. https://doi.org/10.1001/archpsyc.64.6.633.
Keefe RSE, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007 Jun;64(6):633–47.
Keefe, Richard S. E., et al. “Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial.Arch Gen Psychiatry, vol. 64, no. 6, June 2007, pp. 633–47. Pubmed, doi:10.1001/archpsyc.64.6.633.
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, CATIE Investigators, Neurocognitive Working Group. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007 Jun;64(6):633–647.

Published In

Arch Gen Psychiatry

DOI

ISSN

0003-990X

Publication Date

June 2007

Volume

64

Issue

6

Start / End Page

633 / 647

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thiazoles
  • Schizophrenic Psychology
  • Schizophrenia
  • Risperidone
  • Quetiapine Fumarate
  • Psychiatry
  • Piperazines
  • Perphenazine
  • Olanzapine