Healthy Skepticism Library item: 6282

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Publication type: news

Schneider L, Et AL.
Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease
New England Journal of Medicine ( NEJM ) 2006 Oct 12
http://content.nejm.org/cgi/content/short/355/15/1525

Abstract:

NEW ENGLAND JOURNAL OF MEDICINE
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

ABSTRACT
Background Second-generation (atypical) antipsychotic drugs are widely used
to treat psychosis, aggression, and agitation in patients with Alzheimer’s
disease, but their benefits are uncertain and concerns about safety have
emerged. We assessed the effectiveness of atypical antipsychotic drugs in
outpatients with 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 (mean dose, 5.5 mg per day),
quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per
day), or placebo. Doses were adjusted as needed, and patients were followed
for up to 36 weeks. The main outcomes were the time from initial treatment
to the discontinuation of treatment for any reason and the number of
patients with at least minimal improvement on the Clinical Global Impression
of Change (CGIC) scale at 12 weeks.

Results There were no significant differences among treatments with regard
to the time to the discontinuation of treatment for 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
discontinuation of treatment due to a lack of efficacy favored olanzapine
(22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1
weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of
treatment due to adverse events or intolerability favored placebo. Overall,
24% of patients who received olanzapine, 16% of patients who received
quetiapine, 18% of patients who received risperidone, and 5% of patients who
received placebo discontinued their assigned treatment owing to
intolerability (P=0.009). No significant differences were noted among the
groups with regard to improvement on the CGIC scale. Improvement was
observed in 32% of patients assigned to olanzapine, 26% of patients assigned
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 efficacy of 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@usc.edu