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Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial.
Arch Gen Psychiatry. 2007 Jun; 64(6):633-47.AG

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 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.

Authors+Show Affiliations

Department of Psychiatry, John Umstead Hospital, Duke University Medical Center, Durham, NC 27710, USA. richard.keefe@duke.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17548746

Citation

Keefe, Richard S E., et al. "Neurocognitive Effects of Antipsychotic Medications in Patients With Chronic Schizophrenia in the CATIE Trial." Archives of General Psychiatry, vol. 64, no. 6, 2007, pp. 633-47.
Keefe RS, Bilder RM, Davis SM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007;64(6):633-47.
Keefe, R. S., Bilder, R. M., Davis, S. M., Harvey, P. D., Palmer, B. W., Gold, J. M., Meltzer, H. Y., Green, M. F., Capuano, G., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Davis, C. E., Hsiao, J. K., & Lieberman, J. A. (2007). Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Archives of General Psychiatry, 64(6), 633-47.
Keefe RS, et al. Neurocognitive Effects of Antipsychotic Medications in Patients With Chronic Schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007;64(6):633-47. PubMed PMID: 17548746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. AU - Keefe,Richard S E, AU - Bilder,Robert M, AU - Davis,Sonia M, AU - Harvey,Philip D, AU - Palmer,Barton W, AU - Gold,James M, AU - Meltzer,Herbert Y, AU - Green,Michael F, AU - Capuano,George, AU - Stroup,T Scott, AU - McEvoy,Joseph P, AU - Swartz,Marvin S, AU - Rosenheck,Robert A, AU - Perkins,Diana O, AU - Davis,Clarence E, AU - Hsiao,John K, AU - Lieberman,Jeffrey A, AU - ,, AU - ,, PY - 2007/6/6/pubmed PY - 2007/7/4/medline PY - 2007/6/6/entrez SP - 633 EP - 47 JF - Archives of general psychiatry JO - Arch Gen Psychiatry VL - 64 IS - 6 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 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. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/17548746/Neurocognitive_effects_of_antipsychotic_medications_in_patients_with_chronic_schizophrenia_in_the_CATIE_Trial_ L2 - https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/archpsyc.64.6.633 DB - PRIME DP - Unbound Medicine ER -