Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo‐controlled trial

Feldman, Howard; Gauthier, Serge; Hecker, Jane; Vellas, Bruno; Xu, Yichen; Ieni, John R.; Schwam, Elias

doi:10.1002/gps.1325

Cited by 102 publications

(97 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These observations are consistent with the effects of donepezil 10 mg/ day in other studies in patients with severe AD [6,7,19] . Cognition in patients with severe AD receiving 5 mg/day treatment improved significantly.…”

Section: Discussionsupporting

confidence: 82%

Donepezil Treatment of Patients with Severe Alzheimer’s Disease in a Japanese Population: Results from a 24-Week, Double-Blind, Placebo-Controlled, Randomized Trial

Homma

Imai

Tago

et al. 2008

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background/Aims: A 24-week, randomized, parallel-group, double-blind placebo-controlled study was conducted to evaluate the efficacy and tolerability of donepezil in severe Alzheimer’s disease (AD). Methods: Patients with severe AD (Mini-Mental State Examination score 1–12; modified Hachinski Ischemic Score ≤6; Functional Assessment Staging ≧6) were enrolled in this study in Japan. A total of 325 patients were randomized to donepezil 5 mg/day (n = 110), donepezil 10 mg/day (n = 103) or placebo (n = 112). Primary outcome measures were change from baseline to endpoint in the Severe Impairment Battery (SIB) and Clinician’s Interview-Based Impression of Change-plus caregiver input (CIBIC-plus) at the endpoint visit. Results: Donepezil 5 mg/day and 10 mg/day were significantly superior to placebo on the SIB, with a least-squares mean treatment difference of 6.7 and 9.0, respectively (p < 0.001 compared with placebo). CIBIC-plus analyses showed significant differences in favor of donepezil 10 mg/day over placebo at endpoint (p = 0.003). A statistically significant dose-response relationship was demonstrated with the SIB and CIBIC-plus. Donepezil was well tolerated. Conclusion: This study confirmed the effectiveness of donepezil 10 mg/day in patients with severe AD and demonstrated a significant dose-response relationship. Donepezil at dosages of both 5 mg/day and 10 mg/day is safe and well tolerated in Japanese patients with severe AD.

show abstract

Section: Discussionsupporting

confidence: 82%

Donepezil Treatment of Patients with Severe Alzheimer’s Disease in a Japanese Population: Results from a 24-Week, Double-Blind, Placebo-Controlled, Randomized Trial

Homma

Imai

Tago

et al. 2008

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…4 The findings of a study showing that combination therapy with memantine and a cholinesterase inhibitor was more effective than treatment with a cholinesterase inhibitor alone 5 have not been replicated. 6 Results from randomized, controlled trials involving patients with moderate-to-severe 7,8 or severe [9][10][11][12] Alzheimer's disease suggest that cholinesterase inhibitors are associated with modest improvements in cognition and function, and these drugs are approved by the Food and Drug Administration in the United States for the treatment of severe Alzheimer's disease. All the trials involving patients with severe Alzheimer's disease, however, have involved nursing home residents, and none of the trials focusing on moderateto-severe or severe Alzheimer's disease have investigated the strategy of continuing treatment with cholinesterase inhibitors in patients already taking those drugs.…”

Section: Resultsmentioning

confidence: 99%

Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease

Howard¹,

et al. 2012

View full text Add to dashboard Cite

“…A multinational study comparing donepezil to placebo in severely ill patients still in the community showed similar findings. 47 In another study 48 involving a population of patients with moderate-to-severe AD (defined as an MMSE score of 5 to 12) but still living in the community, similar dosages of donepezil showed large effects on the SIB (7.42, P = 0.0017) and the MMSE (1.99, P = 0.0022) after 6 months, compared with placebo; equivalent measures of ADL, global change, and the NPI were significantly different. It is thus clear that there may be measurable benefits in treating patients suffering from moderate-to-severe AD with donepezil if they have never had a therapeutic trial with a ChEI.…”

Section: Cholinesterase Inhibitorsmentioning

confidence: 95%