Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
Jeffrey A. Lieberman, M.D., T. Scott Stroup, M.D., M.P.H., Joseph P. McEvoy, M.D., Marvin S. Swartz, M.D., Robert A. Rosenheck, M.D., Diana O. Perkins, M.D., M.P.H., Richard S.E. Keefe, Ph.D., Sonia M. Davis, Dr.P.H., Clarence E. Davis, Ph.D., Barry D. Lebowitz, Ph.D., Joanne Severe, M.S., John K. Hsiao, M.D., for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators
Background The relative effectiveness of second-generation (atypical)antipsychotic drugs as compared with that of older agents hasbeen incompletely addressed, though newer agents are currentlyused far more commonly. We compared a first-generation antipsychotic,perphenazine, with several newer drugs in a double-blind study.
Methods A total of 1493 patients with schizophrenia were recruitedat 57 U.S. sites and randomly assigned to receive olanzapine(7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine(200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day)for up to 18 months. Ziprasidone (40 to 160 mg per day) wasincluded after its approval by the Food and Drug Administration.The primary aim was to delineate differences in the overalleffectiveness of these five treatments.
Results Overall, 74 percent of patients discontinued the studymedication before 18 months (1061 of the 1432 patients who receivedat least one dose): 64 percent of those assigned to olanzapine,75 percent of those assigned to perphenazine, 82 percent ofthose assigned to quetiapine, 74 percent of those assigned torisperidone, and 79 percent of those assigned to ziprasidone.The time to the discontinuation of treatment for any cause wassignificantly longer in the olanzapine group than in the quetiapine(P<0.001) or risperidone (P=0.002) group, but not in theperphenazine (P=0.021) or ziprasidone (P=0.028) group. The timesto discontinuation because of intolerable side effects weresimilar among the groups, but the rates differed (P=0.04); olanzapinewas associated with more discontinuation for weight gain ormetabolic effects, and perphenazine was associated with morediscontinuation for extrapyramidal effects.
Conclusions The majority of patients in each group discontinuedtheir assigned treatment owing to inefficacy or intolerableside effects or for other reasons. Olanzapine was the most effectivein terms of the rates of discontinuation, and the efficacy ofthe conventional antipsychotic agent perphenazine appeared similarto that of quetiapine, risperidone, and ziprasidone. Olanzapinewas associated with greater weight gain and increases in measuresof glucose and lipid metabolism.
Source Information
From the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York (J.A.L.); the Department of Psychiatry, School of Medicine (T.S.S., D.O.P.), and the Department of Biostatistics, School of Public Health (S.M.D., C.E.D.), University of North Carolina at Chapel Hill, Chapel Hill; Quintiles, Research Triangle Park, N.C. (S.M.D.); the Department of Biological Psychiatry, John Umstead Hospital, Butner, N.C. (J.P.M.); the Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, N.C. (J.P.M., M.S.S., R.S.E.K.); the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (R.A.R.); and the Division of Services and Intervention Research, National Institute of Mental Health, National Institutes of Health, Bethesda, Md. (B.D.L., J.S., J.K.H.).
Address reprint requests to Dr. Lieberman at the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, 1051 Riverside Dr., New York, NY 10032, or at jlieberman{at}columbia.edu.
Antipsychotic Drugs and Schizophrenia
Dettling M., Anghelescu I.-G., Essock S. M., Covell N. H., Jackson C. T., Gupta N., Basu D., Duan N., Kraemer H. C., Mintz J., Lieberman J. A., Stroup T. S., Davis S. M., the CATIE Investigator Group
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N Engl J Med 2006;
354:298-300, Jan 19, 2006.
Correspondence
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