Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease
Lon S. Schneider, M.D., Pierre N. Tariot, M.D., Karen S. Dagerman, M.S., Sonia M. Davis, Dr.P.H., John K. Hsiao, M.D., M. Saleem Ismail, M.D., Barry D. Lebowitz, Ph.D., Constantine G. Lyketsos, M.D., M.H.S., J. Michael Ryan, M.D., T. Scott Stroup, M.D., David L. Sultzer, M.D., Daniel Weintraub, M.D., Jeffrey A. Lieberman, M.D., for the CATIE-AD Study Group
Background Second-generation (atypical) antipsychotic drugsare widely used to treat psychosis, aggression, and agitationin patients with Alzheimer's disease, but their benefits areuncertain and concerns about safety have emerged. We assessedthe effectiveness of atypical antipsychotic drugs in outpatientswith Alzheimer's disease.
Methods In this 42-site, double-blind, placebo-controlled trial,421 outpatients with Alzheimer's disease and psychosis, aggression,or agitation were randomly assigned to receive olanzapine (meandose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day),risperidone (mean dose, 1.0 mg per day), or placebo. Doses wereadjusted as needed, and patients were followed for up to 36weeks. The main outcomes were the time from initial treatmentto the discontinuation of treatment for any reason and the numberof patients with at least minimal improvement on the ClinicalGlobal Impression of Change (CGIC) scale at 12 weeks.
Results There were no significant differences among treatmentswith regard to the time to the discontinuation of treatmentfor any reason: olanzapine (median, 8.1 weeks), quetiapine (median,5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median,8.0 weeks) (P=0.52). The median time to the discontinuationof treatment due to a lack of efficacy favored olanzapine (22.1weeks) and risperidone (26.7 weeks) as compared with quetiapine(9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to thediscontinuation of treatment due to adverse events or intolerabilityfavored placebo. Overall, 24% of patients who received olanzapine,16% of patients who received quetiapine, 18% of patients whoreceived risperidone, and 5% of patients who received placebodiscontinued their assigned treatment owing to intolerability(P=0.009). No significant differences were noted among the groupswith regard to improvement on the CGIC scale. Improvement wasobserved in 32% of patients assigned to olanzapine, 26% of patientsassigned to quetiapine, 29% of patients assigned to risperidone,and 21% of patients assigned to placebo (P=0.22).
Conclusions Adverse effects offset advantages in the efficacyof atypical antipsychotic drugs for the treatment of psychosis,aggression, or agitation in patients with Alzheimer's disease.(ClinicalTrials.gov number, NCT00015548
[ClinicalTrials.gov]
.)
Source Information
From the Keck School of Medicine, University of Southern California, Los Angeles (L.S.S., K.S.D.); the Banner Alzheimer's Institute, Phoenix, AZ (P.N.T.); Quintiles, Research Triangle Park, NC (S.M.D.); the National Institute of Mental Health, National Institutes of Health, Bethesda, MD (J.K.H.); the University of Rochester Medical Center, Rochester, NY (M.S.I., J.M.R.); the School of Medicine, University of California, San Diego, La Jolla (B.D.L.); the Department of Psychiatry, Johns Hopkins Bayview, Johns Hopkins University, Baltimore (C.G.L.); the School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (T.S.S.); Veterans Affairs Greater Los Angeles Healthcare System, University of California, Los Angeles, Los Angeles (D.L.S.); the School of Medicine, University of Pennsylvania, Philadelphia (D.W.); and the College of Physicians and Surgeons, New York (J.A.L.).
Address reprint requests to Dr. Schneider at the Keck School of Medicine, University of Southern California, 1510 San Pablo St., HCC 600, Los Angeles, CA 90033, or at lschneid{at}usc.edu.
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