A 24-week, Double-Blind, Placebo-Controlled Trial of Donepezil in Patients With Alzheimer's Disease. Donepezil Study Group

Neurology. 1998 Jan;50(1):136-45. doi: 10.1212/wnl.50.1.136.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Cholinesterase Inhibitors / administration & dosage*
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / blood
  • Cognition / drug effects
  • Donepezil
  • Double-Blind Method
  • Female
  • Humans
  • Indans / administration & dosage*
  • Indans / adverse effects
  • Indans / blood
  • Male
  • Memory / drug effects
  • Mental Status Schedule
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Piperidines / blood

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Donepezil