Donepezil was no better than placebo for agitation in patients with Alzheimer disease.

M e t h o d s Design: Randomized placebo-controlled trial. Allocation: Concealed.* Blinding: Blinded (patients and caregivers, clinicians, outcome assessors, and {data monitoring committee}†).* Follow-up period: 12 weeks. Setting: 8 clinical centers in England, United Kingdom. Patients: 259 patients > 39 years of age (mean age 85 y, 85% women) who had probable or possible Alzheimer disease (on the basis of National Institute of Neurological and Communication Disorders and Stroke—Alzheimer’s Disease and Related Disorders Association criteria); had clinical agitation (patient distress, at least moderate management problems for caregivers ≥ 2 d/wk for 2 wk, and a Cohen–Mansfield Agitation Inventory [CMAI] score ≥ 39); lived in a residential care facility or with a caregiver in the community; had not received neuroleptic agents or cholinesterase inhibitors in the previous 4 weeks and were not to receive such drugs in the following 16 weeks; and were able to give consent or to assent with caregiver agreement. Exclusion criteria were sensitivity to donepezil; severe, unstable, or uncontrolled medical conditions; delirium; dementia with Lewy bodies; and evidence of poor compliance with medications. Intervention: Donepezil, 5 mg/d for 4 weeks and 10 mg/d for 8 weeks (n = 128), or placebo (n = 131). Outcomes: Change in CMAI score (scores of 29 to 203; higher scores indicate more severe or frequent agitation) and treatment response (> 30% reduction in agitation). The study had 90% power to detect a 25% difference between groups in patients who responded to treatment (α = 0.05). Patient follow-up: 88% (intention-to-treat analysis).