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Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder

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Abstract

Background

Newer antipsychotic medications have been reported to enhance cognitive functioning in schizophrenia. Head to head studies with double-blind methods are still relatively few in number.

Objectives

To compare the relative cognitive enhancing effects of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.

Procedures

In this 6-week, multicenter, double-blind, parallel-designed trial, patients were randomized to ziprasidone or olanzapine. No patient who had ever received a complete treatment trial with either of these medications previously was entered into the study. Cognitive testing measuring attention, motor speed, memory, executive functioning, and verbal skills were performed on all patients at baseline and endpoint.

Results

Treatment with either ziprasidone or olanzapine was associated with statistically significant improvements from baseline in attention, memory, working memory, motor speed, and executive functions. Treatment with olanzapine was also associated with a statistically significant improvement in verbal fluency. No statistically significant differences between these medications were found in the magnitude of improvement from baseline on any of the cognitive measures (other than verbal fluency in an exploratory analysis). Observed changes were not associated with changes in clinical symptoms measured using the PANSS or changes in movement disorders.

Conclusions

During 6 weeks of treatment, ziprasidone and olanzapine demonstrated substantial and comparable cognitive-enhancing effects relative to previous treatment. These effects were noted in all aspects of cognitive functioning previously proven to predict functional outcome in schizophrenia. No overall differences were detected between the medications in terms of the extent of cognitive enhancement.

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Acknowledgements

This research was supported by Pfizer, Inc. The authors acknowledge and thank the following co-investigators: W.M. Abi-Saab, M.D., and J. Krystal, M.D. (Yale University School of Medicine, New Haven, CT); A. Aleem, M.D. (Anxiety Disorders Institute of Atlanta, Atlanta, GA); E. Allan M.D. (Hudson Valley VA Health Care System, Montrose, NY); J. Ananth, M.D. (University of California Harbor/UCLA Medical Center, Torrance, CA); M. Bari, M.D. (Synergy Clinical Research Center, Chula Vista, CA); R. Brenner, M.D. (Neurobehavioral Research, Inc. Lawrence, NY); J.M. Carr, M.D. (Affiliated Research Institute, Loma Linda, CA); F. Centorrino, M.D. (Bipolar and Psychotic Disorders Program, Belmont, MA); S. Cheren, M.D. (Access Clinical Trials, Natick, MA); J.E. Cueva, M.D. (St. Vincent’s Hospital and Medical Center, New York, NY); G. Ramanath, M.D. (Innovative Clinical Solutions, Ltd., Washington, Falls Church, VA); A.M. Freeman III, M.D. (The Psychopharmacology Research Clinic, Shreveport, LA); W.C. Fuller, M.D. (USD School of Medicine, Sioux Falls, SD); A.J. Gelenberg, M.D. (The University of Arizona Health Sciences Center, Tucson, AZ); G. Grossberg, M.D. and H. Asif, M.D. (St. Louis University, St. Louis, MO); H. Harsch, M.D. (The Medical College of Wisconsin, Milwaukee, WI); R. Horne, M.D. (Lake Mead Hospital, Las Vegas, NV); T.K. Johnson, PharmD (California Neuropsychopharmacology Clinical Research Institute (CNRI), San Diego, CA); P. Keck, M.D. (Psychiatric Professional Services, Inc., University of Cincinnati, OH); M.A. Knesvich, M.D. (St. Paul Medical Center, Dallas, TX); M. Levy, M.D. (Staten Island University Hospital, New York, NY); A.F. Lowy, M.D. (Comprehensive NeuroScience, Inc., Washington, DC); H. Meltzer, M.D. (Psychiatric Hospital at Vanderbilt University, Nashville, TN); C.H. Merideth, M.D. (Affiliated Research Institute, San Diego, CA); R. Pearlman, M.D. (Sisters of Charity Medical Center, Staten Island, NY); M.G. Plopper, M.D. (Sharp Mesa Vista Hospital, San Diego, CA); T. Reid, M.D. (ICSL Clinical Studies, Melbourne, FL); S. Riggio, M.D. (Mount Sinai Medical Center, New York, NY); S. Risch, M.D. (Medical University of South Carolina, Charleston, SC); M. Roffman, Ph.D., MBA (ClinSearch, Inc., Summit, NJ); B. Rosen, M.D. (North Shore Psychiatric Consultants, Smithtown, NY); D. Sack, M.D. (The Institute for Psychopharmacology Research of Orange County, Cerritos, CA); F.W. Schaerf, M.D., Ph.D. (Medical Studies Florida, Fort Meyers, FL); R.T. Segraves, M.D. (MetroHealth Medical Center, Cleveland, OH); R. Steinbook, M.D. (University of Miami/Jackson Memorial Medical Center, Miami, FL); A.A. Sugerman, M.D. (Princeton Biomedical Research, P.A., Princeton, NJ); J. Wolberg, M.D. (Mount Sinai Medical Center, New York, NY); L.W. Adler, M.D. (Clinical Insights, Inc., Glen Burnie, MD); N. Bark, M.D. (Bronx Psychiatric Center, Bronx, NY); I. Berman, M.D. (Taunton State Hospital, Taunton, MA); D. Garver, M.D. (Dallas Veterans Affairs Medical Center, Dallas, TX); M.R. Gershberg, M.D. (North General Hospital, New York, NY); R.E. Gur, M.D., Ph.D. (University of Pennsylvania Medical Center Neuropsychiatry Program, Philadelphia, PA); R. Mofsen, D.O. (Clinical Research Associates, P.C., St. Louis, MO); J.J. Pahl, M.D., FCP (Pahl Brain Associates, P.C., Oklahoma City, OK); J.D. Raese, M.D. (Dr. Raese and Associates, Riverside, CA); S. Targum, M.D. (Clinical Studies, Philadelphia, Philadelphia, PA); N.W. Telew, M.D. (Oregon Center for Clinical Investigations, Inc. Eugene, OR); S. Vivek, M.D. (Jamaica Hospital Medical Center, Jamaica, NY); A. Winokur, M.D. (University of Connecticut, Farmington, CT); D. Zimbroff, M.D. (Pacific Clinical Research, Upland, CA).

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Authors and Affiliations

  1. Department of Psychiatry, Mount Sinai School of Medicine, Box 1229, New York, NY 10029, USA

    Philip D. Harvey

  2. Pfizer Inc., New York, NY, USA

    Cynthia O. Siu & Steven Romano

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  1. Philip D. Harvey
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  2. Cynthia O. Siu
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Correspondence to Philip D. Harvey.

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Harvey, P.D., Siu, C.O. & Romano, S. Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Psychopharmacology 172, 324–332 (2004). https://doi.org/10.1007/s00213-003-1652-2

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  • DOI: https://doi.org/10.1007/s00213-003-1652-2

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