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Comparative Effect of Atypical and Conventional Antipsychotic Drugs on Neurocognition in First-Episode Psychosis: A Randomized, Double-Blind Trial of Olanzapine Versus Low Doses of Haloperidol

Keefe, Richard S.E., Seidman, Larry J., Christensen, Bruce K., Hamer, Robert M., Sharma, Tonmoy, Sitskoorn, Margriet M., Lewine, Richard R.J., Yurgelun-Todd, Deborah A., Gur, Ruben C., Tohen, Mauricio, Tollefson, Gary D., Sanger, Todd M., Lieberman, Jeffrey A., HGDH Research Group·2004·American Journal of Psychiatry

DOI 10.1176/appi.ajp.161.6.985

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Abstract

OBJECTIVE: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. RESULTS: An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. CONCLUSIONS: Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

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Authors: Keefe, R. S. E., Seidman, L. J., Christensen, B. K., Hamer, R. M., Sharma, T., Sitskoorn, M. M., Lewine, R. R. J., Yurgelun-Todd, D. A., Gur, R. C., Tohen, M., Tollefson, G. D., Sanger, T. M., Lieberman, J. A., & HGDH Research Group
Affiliations: Duke University (US)
ORCID: Keefe, Richard S.E.
Seidman, Larry J.
Christensen, Bruce K.
Sitskoorn, Margriet M.
Yurgelun-Todd, Deborah A.
Gur, Ruben C.
Tohen, Mauricio
Sanger, Todd M.
Lieberman, Jeffrey A.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2004-06-01
Volume: 161
Issue: 6
Pages: 985-995
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.161.6.985
OpenAlex: W2145453003
Cited by: 314
References: 47
Citations by year: 2026: 1 · 2025: 2 · 2024: 4 · 2023: 12 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 12 · 2014: 9 · 2013: 14 · 2012: 12
FWCI: 24.47
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords: olanzapine, haloperidol, first-episode psychosis, neurocognitive function, atypical antipsychotics, typical antipsychotics, schizophrenia, schizoaffective disorder, verbal fluency, working memory, verbal memory, sustained attention, anticholinergic effects, extrapyramidal symptoms, IQ, disease duration
MeSH terms: Olanzapine, Adolescent, Adult, Basal Ganglia Diseases, Benzodiazepines, Cognition Disorders, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Haloperidol, Humans, Male, Neuropsychological Tests, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Treatment Outcome, Principal Component Analysis

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Comparative Effect of Atypical and Conventional Antipsychotic Drugs on Neurocognition in First-Episode Psychosis: A Randomized, Double-Blind Trial of Olanzapine Versus Low Doses of Haloperidol

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