A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease

TLDR

The study evaluated the efficacy and safety of donepezil in patients with mild to moderate Alzheimer's disease in a multicenter, double‑blind trial. Patients were randomized to placebo, 5‑mg/d, or 10‑mg/d donepezil for 24 weeks with a 6‑week washout, and efficacy was assessed using ADAS‑cog, CIBIC plus, MMSE, CDR‑SB, and QoL. Donepezil at 5‑mg/d and 10‑mg/d significantly improved cognition (ADAS‑cog) and global function (CIBIC plus) versus placebo at weeks 12–24, with benefits also seen on MMSE and CDR‑SB but not QoL, effects waned after washout, and the drug was well tolerated with mild, transient cholinergic side effects.

Abstract

The efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD) was investigated in a multicenter, double-blind study. Patients were randomly assigned to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154), or 10 mg/d donepezil (n = 157) for 24 weeks followed by a 6-week, single-blind placebo washout. The primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinician's Interview Based Assessment of Change-Plus (CIBIC plus), with the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB), and patient rated Quality of Life (QoL) used as secondary measures. Cognitive function, as measured by the ADAS-cog, was significantly improved in the 5- and 10-mg/d donepezil groups as compared with the placebo group at weeks 12, 18, and 24. Clinician's global ratings on the CIBIC plus also improved in both the 5- and 10-mg/d donepezil groups relative to placebo. At the end of the 6-week placebo washout phase, ADAS-cog scores and CIBIC plus ratings were not significantly different for the three groups. Significant treatment benefits were also observed consistently in both the 5- and 10-mg/d groups on the MMSE and the CDR-SB, but there was no consistent effect on the patient-rated QoL. Cholinergic side effects (primarily diarrhea, nausea, and vomiting) were reported more often in the 10-mg/d group than either the 5-mg/d or placebo groups. Side effects were transient and generally mild in severity. These data indicate that donepezil is a well-tolerated drug that improves cognition and global function in patients with mild to moderate AD.