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Previous Volume 353:1209-1223 September 22, 2005 Number 12 Next

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ABSTRACT

Background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used 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 recruited at 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) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments.

Results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects.

Conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of 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.

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