• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (259)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Neurology  • Cognitive Disorders  • Neurology, Other  • Psychiatry  • Psychopharmacology  • Schizophrenia  • Alert me on articles by topic  Social Bookmarking   What's this?

Richard S. E. Keefe, PhD; Robert M. Bilder, PhD; Sonia M. Davis, DrPH; Philip D. Harvey, PhD; Barton W. Palmer, PhD; James M. Gold, PhD; Herbert Y. Meltzer, MD; Michael F. Green, PhD; George Capuano, PhD; T. Scott Stroup, MD, MPH; Joseph P. McEvoy, MD; Marvin S. Swartz, MD; Robert A. Rosenheck, MD; Diana O. Perkins, MD, MPH; Clarence E. Davis, PhD; John K. Hsiao, MD; Jeffrey A. Lieberman, MD; for the CATIE Investigators and the Neurocognitive Working Group

Arch Gen Psychiatry. 2007;64(6):633-647.

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.

Author Affiliations: Departments of Psychiatry and Behavioral Sciences (Drs Keefe, McEvoy, and Swartz) and Biological Psychiatry, John Umstead Hospital (Dr McEvoy), Duke University Medical Center, Durham, NC; Departments of Psychiatry and Biobehavioral Sciences (Drs Bilder and Green) and Psychology (Dr Bilder), University of California, Los Angeles, Neuropsychiatric Institute; Quintiles Inc, Research Triangle Park, NC (Dr Davis); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (Dr Harvey); Department of Psychiatry, University of California, San Diego (Dr Palmer); Maryland Psychiatric Research Center, Baltimore (Dr Gold); Department of Psychiatry, Vanderbilt University Medical Center, Nashville, Tenn (Dr Meltzer); Department of Psychiatry, School of Medicine (Drs Capuano, Stroup, and Perkins), and Department of Biostatistics (Dr Davis), University of North Carolina at Chapel Hill; Department of Psychiatry, Yale University School of Medicine, New Haven, Conn (Dr Rosenheck); Adult Psychopharmacology Program, Adult Treatment and Preventive Intervention Research Branch, Division of Services and Intervention Research, National Institute of Mental Health, Bethesda, Md (Dr Hsiao); and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York (Dr Lieberman).

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Cognitive Improvement in Response to Antipsychotic Drugs: Neurocognitive Effects of Antipsychotic Medications in Patients With Chronic Schizophrenia in the CATIE Trial
R. Walter Heinrichs
Arch Gen Psychiatry. 2007;64(6):631-632.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Therapeutic effects of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms
Shifu et al.
Aust N Z J Psychiatry 2012;46:153-160.
ABSTRACT | FULL TEXT  

Dopamine D2 Receptor Occupancy and Cognition in Schizophrenia: Analysis of the CATIE Data
Sakurai et al.
Schizophr Bull 2012;0:sbr189v1-sbr189.
ABSTRACT | FULL TEXT  

Cognitive Factor Structure and Invariance in People With Schizophrenia, Their Unaffected Siblings, and Controls
Dickinson et al.
Schizophr Bull 2011;37:1157-1167.
ABSTRACT | FULL TEXT  

The FDA-NIMH-MATRICS Guidelines for Clinical Trial Design of Cognitive-Enhancing Drugs: What Do We Know 5 Years Later?
Buchanan et al.
Schizophr Bull 2011;37:1209-1217.
ABSTRACT | FULL TEXT  

GABAergic Precursor Transplantation into the Prefrontal Cortex Prevents Phencyclidine-Induced Cognitive Deficits
Tanaka et al.
J. Neurosci. 2011;31:14116-14125.
ABSTRACT | FULL TEXT  

Evaluation of state and trait biomarkers in healthy volunteers for the development of novel drug treatments in schizophrenia
Koychev et al.
J Psychopharmacol 2011;25:1207-1225.
ABSTRACT | FULL TEXT  

Report From the Working Group Conference on Multisite Trial Design for Cognitive Remediation in Schizophrenia
Keefe et al.
Schizophr Bull 2011;37:1057-1065.
ABSTRACT | FULL TEXT  

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats
Horiguchi et al.
J. Pharmacol. Exp. Ther. 2011;338:605-614.
ABSTRACT | FULL TEXT  

PD168077, a D4 receptor agonist, reverses object recognition deficits in rats: potential role for D4 receptor mechanisms in improving cognitive dysfunction in schizophrenia
Sood et al.
J Psychopharmacol 2011;25:792-800.
ABSTRACT | FULL TEXT  

Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology
Barnes and the Schizophrenia Consensus Group of the British A
J Psychopharmacol 2011;25:567-620.
ABSTRACT | FULL TEXT  

Cognitive Efficacy of Quetiapine and Olanzapine in Early-Onset First-Episode Psychosis
Robles et al.
Schizophr Bull 2011;37:405-415.
ABSTRACT | FULL TEXT  

Questioning the 'neuroprotective' hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia?
Moncrieff
Br. J. Psychiatry 2011;198:85-87.
ABSTRACT | FULL TEXT  

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results From a 2-Year Randomized Trial
Eack et al.
Research on Social Work Practice 2011;21:32-42.
ABSTRACT  

Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group
Simonsen et al.
Schizophr Bull 2011;37:73-83.
ABSTRACT | FULL TEXT  

Intrinsic Motivation Inventory: An Adapted Measure for Schizophrenia Research
Choi et al.
Schizophr Bull 2010;36:966-976.
ABSTRACT | FULL TEXT  

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity
Dawson et al.
Schizophr Bull 2010;0:sbq090v1-sbq090.
ABSTRACT | FULL TEXT  

Cognitive Functioning and Disability in Schizophrenia
Harvey
Current Directions in Psychological Science 2010;19:249-254.
ABSTRACT | FULL TEXT  

Neuroprotective Effects of Cognitive Enhancement Therapy Against Gray Matter Loss in Early Schizophrenia: Results From a 2-Year Randomized Controlled Trial
Eack et al.
Arch Gen Psychiatry 2010;67:674-682.
ABSTRACT | FULL TEXT  

Neurocognitive Decline in Early-Onset Schizophrenia Compared With ADHD and Normal Controls: Evidence From a 13-Year Follow-up Study
Oie et al.
Schizophr Bull 2010;36:557-565.
ABSTRACT | FULL TEXT  

Cognitive Performance and Functional Competence as Predictors of Community Independence in Schizophrenia
Heinrichs et al.
Schizophr Bull 2010;36:381-387.
ABSTRACT | FULL TEXT  

Attenuation of Phencyclidine-Induced Object Recognition Deficits by the Combination of Atypical Antipsychotic Drugs and Pimavanserin (ACP 103), a 5-Hydroxytryptamine2A Receptor Inverse Agonist
Snigdha et al.
J. Pharmacol. Exp. Ther. 2010;332:622-631.
ABSTRACT | FULL TEXT  

Anticipating DSM-V: Opportunities and Challenges for Cognition and Psychosis
Barch and Keefe
Schizophr Bull 2010;36:43-47.
FULL TEXT  

Cognitive Impairment in Affective Psychoses: A Meta-analysis
Bora et al.
Schizophr Bull 2010;36:112-125.
ABSTRACT | FULL TEXT  

Population Pharmacokinetics of Perphenazine in Schizophrenia Patients From CATIE: Impact of Race and Smoking
Jin et al.
J Clin Pharmacol 2010;50:73-80.
ABSTRACT | FULL TEXT  

Diminished Orientation-Specific Surround Suppression of Visual Processing in Schizophrenia
Yoon et al.
Schizophr Bull 2009;35:1078-1084.
ABSTRACT | FULL TEXT  

Aberrant Frontoparietal Function during Recognition Memory in Schizophrenia: A Multimodal Neuroimaging Investigation
Weiss et al.
J. Neurosci. 2009;29:11347-11359.
ABSTRACT | FULL TEXT  

Principles of Antipsychotic Prescribing for Policy Makers, Circa 2008. Translating Knowledge to Promote Individualized Treatment
Parks et al.
Schizophr Bull 2009;35:931-936.
ABSTRACT | FULL TEXT  

Developing A Policy For Second-Generation Antipsychotic Drugs
Rosenheck and Sernyak
Health Aff (Millwood) 2009;28:w782-w793.
ABSTRACT | FULL TEXT  

Time-Lapse Mapping of Cortical Changes in Schizophrenia with Different Treatments
Thompson et al.
Cereb Cortex 2009;19:1107-1123.
ABSTRACT | FULL TEXT  

Cognitive effectiveness of olanzapine and risperidone in first-episode psychosis
Cuesta et al.
Br. J. Psychiatry 2009;194:439-445.
ABSTRACT | FULL TEXT  

Cross-sectional and Longitudinal Relationships Between Insight and Attitudes Toward Medication and Clinical Outcomes in Chronic Schizophrenia
Mohamed et al.
Schizophr Bull 2009;35:336-346.
ABSTRACT | FULL TEXT  

Attention Shaping: a Reward-Based Learning Method to Enhance Skills Training Outcomes in Schizophrenia
Silverstein et al.
Schizophr Bull 2009;35:222-232.
ABSTRACT | FULL TEXT  

Transient and selective overexpression of D2 receptors in the striatum causes persistent deficits in conditional associative learning
Bach et al.
Proc. Natl. Acad. Sci. USA 2008;105:16027-16032.
ABSTRACT | FULL TEXT  

Extrapyramidal side-effects of antipsychotics in a randomised trial
Miller et al.
Br. J. Psychiatry 2008;193:279-288.
ABSTRACT | FULL TEXT  

Antipsychotic Medication Utilization Trends Among Texas Veterans: 1997-2002
Yang et al.
The Annals of Pharmacotherapy 2008;42:1229-1238.
ABSTRACT | FULL TEXT  

Measuring Specific, Rather than Generalized, Cognitive Deficits and Maximizing Between-Group Effect Size in Studies of Cognition and Cognitive Change
Silverstein
Schizophr Bull 2008;34:645-655.
ABSTRACT | FULL TEXT  

Measurement Issues in the Use of Cognitive Neuroscience Tasks in Drug Development for Impaired Cognition in Schizophrenia: A Report of the Second Consensus Building Conference of the CNTRICS Initiative
Barch et al.
Schizophr Bull 2008;34:613-618.
ABSTRACT | FULL TEXT  

Preclinical Characterization of Selective Phosphodiesterase 10A Inhibitors: A New Therapeutic Approach to the Treatment of Schizophrenia
Schmidt et al.
J. Pharmacol. Exp. Ther. 2008;325:681-690.
ABSTRACT | FULL TEXT  

Randomized Controlled Trials for Schizophrenia: Study Designs Targeted to Distinct Goals
Stroup and Geddes
Schizophr Bull 2008;34:266-274.
ABSTRACT | FULL TEXT  

CATIE and CUtLASS: can we handle the truth?
Lewis and Lieberman
Br. J. Psychiatry 2008;192:161-163.
ABSTRACT | FULL TEXT  

The Orexins/Hypocretins and Schizophrenia
Deutch and Bubser
Schizophr Bull 2007;33:1277-1283.
ABSTRACT | FULL TEXT  

Cognitive Improvement After Treatment With Second-Generation Antipsychotic Medications in First-Episode Schizophrenia: Is It a Practice Effect?
Goldberg et al.
Arch Gen Psychiatry 2007;64:1115-1122.
ABSTRACT | FULL TEXT  

Recent Advances in the Development of Novel Pharmacological Agents for the Treatment of Cognitive Impairments in Schizophrenia
Buchanan et al.
Schizophr Bull 2007;33:1120-1130.
ABSTRACT | FULL TEXT  

Do Antipsychotic Drugs Improve Cognitive Function in Schizophrenia?
JWatch Psychiatry 2007;2007:4-4.
FULL TEXT  

Cognitive Improvement in Response to Antipsychotic Drugs: Neurocognitive Effects of Antipsychotic Medications in Patients With Chronic Schizophrenia in the CATIE Trial
Heinrichs
Arch Gen Psychiatry 2007;64:631-632.
FULL TEXT