Donepezil in vascular dementia: a randomized, placebo-controlled study

Topic: Risk, prevention and care in population studies

Objective To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia (VaD). Methods Patients (n = 616; mean age, 75.0 years) with probable or possible VaD, according to National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche en l'Enseignement en Neurosciences criteria, were randomized to receive donepezil 5 mg/day (n = 208), donepezil 10 mg/day (after 5 mg/day for the first 28 days) (n = 215), or placebo (n = 193) for 24 weeks. Results Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3% of the 10 mg donepezil group and 80.8% of the 5 mg group completed the study compared with 83.4% of the placebo group. Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer's Disease Assessment Scale-cognitive subscale compared with placebo, with a mean endpoint treatment difference, as measured by the change from baseline score, of approximately 2 points (donepezil 5 mg, -1.65 [p = 0.003]; 10 mg, -2.09 [p = 0.0002]). Greater improvements on the Clinician's Interview-Based Impression of Change-plus version were observed with both donepezil groups than with the placebo group (overall donepezil treatment vs placebo p = 0.008); 25% of the placebo group showed improvement compared with 39% (p = 0.004) of the 5 mg group and 32% (p = 0.047) of the 10 mg group. Withdrawal rates due to adverse events were low (placebo, 8.8%; donepezil 5 mg, 10.1%; 10 mg, 16.3%). Conclusions Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients, and donepezil was well tolerated.

Key findings

• Results Seventy-six percent of the patients enrolled had probable VaD.
• A total of 75.3% of the 10 mg donepezil group and 80.8% of the 5 mg group completed the study compared with 83.4% of the placebo group.
• Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer's Disease Assessment Scale-cognitive subscale compared with placebo, with a mean endpoint treatment difference, as measured by the change from baseline score, of approximately 2 points (donepezil 5 mg, -1.65 [p = 0.003]; 10 mg, -2.09 [p = 0.0002]).
• Greater improvements on the Clinician's Interview-Based Impression of Change-plus version were observed with both donepezil groups than with the placebo group (overall donepezil treatment vs placebo p = 0.008); 25% of the placebo group showed improvement compared with 39% (p = 0.004) of the 5 mg group and 32% (p = 0.047) of the 10 mg group.
• Conclusions Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients, and donepezil was well tolerated.

Study details

• Participants616
• Effect size75.3%; 80.8%; 83.4%
• Evidence strengthHigh

Read the original

• DOI: 10.1212/01.wnl.0000078943.50032.fc
• PubMed: 12939421
• Original source →

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@article{wilkinson2003-12939421,
  author  = {Wilkinson, D. and Doody, R. and Helme, R. and Taubman, K. and Mintzer, J. and Kertesz, A. and Pratt, R. D. and {Donepezil 308 Study Group}},
  title   = {{Donepezil in vascular dementia: a randomized, placebo-controlled study}},
  journal = {Neurology},
  year    = {2003},
  doi     = {10.1212/01.wnl.0000078943.50032.fc},
  pmid    = {12939421},
  url     = {https://doi.org/10.1212/01.wnl.0000078943.50032.fc}
}

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