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A Double-blind, Randomized, Placebo-Controlled Trial

Jamie S. Street, MD; W. Scott Clark, PhD; Kimberley S. Gannon, PhD; Jeffrey L. Cummings, MD; Frank P. Bymaster, MSc; Roy N. Tamura, PhD; Steven J. Mitan, BSc; Deborah L. Kadam, MA; Todd M. Sanger, PhD; Peter D. Feldman, PhD; Gary D. Tollefson, MD, PhD; Alan Breier, MD; for the HGEU Study Group

Arch Gen Psychiatry. 2000;57:968-976.

Background  Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD.

Methods  A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory–Nursing Home version.

Results  Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3.7 [P = .006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P = .008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo.

Conclusion  Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.

From the Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind (Drs Street, Clark, Gannon, Tamura, Sanger, Feldman, Tollefson, and Breier, Messrs Bymaster and Mitan, and Ms Kadam); and Departments of Neurology and Psychiatry and Biobehavioral Sciences, Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, Calif (Dr Cummings). Drs Street, Clark, Tamura, Sanger, Feldman, Tollefson, and Breier, Messrs Bymaster and Mitan, and Ms Kadam are stockholders in Eli Lilly and Company, a sponsor of this study.

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