Olanzapine treatment of psychotic and behavioral symptoms in patients withAlzheimer disease in nursing care facilities - A double-blind, randomized,placebo-controlled trial

Background: Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregi ver 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 co nducted in 206 elderly US nursing home residents with AD who exhibited psyc hotic and/or behavioral symptoms. Patients were randomly assigned to placeb o 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 Delusi ons items (Core Total) of the Neuropsychiatric Inventory- Nursing Home vers ion. Results: Low-dose olanzapine (5 and 10 mg/d) produced significant improveme nt 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 Disrupt iveness score, reflecting the impact of patients' psychosis and behavioral disturbances on die caregiver, was significantly reduced in the 5-mg/d olan zapine group compared with placebo (-2.7 vs -1.5; P=.008). Somnolence was s ignificantly 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 1 7.0%, respectively). No significant cognitive impairment, increase in extra pyramidal symptoms, or central anticholinergic effects were found at any ol anzapine 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 psychosi s in this population of patients with AD.