donepezil clinical trials

Introduction

-> Cochrane Review. In: The Cochrane Library 2001, 2003

Reviewer's conclusions:

• donepezil produced modest improvement in cognitive function for people with mild to moderate Alzheimer's disease treated for 12-52 weeks
• global clinical state rated more positively by study clinicians in treated patients vs controls
• No benefit in self-assessed quality of life
• data on many important outcomes is not available
• practical importance of benefits to patients & caregivers is unclear

Methods:

• 8 controlled trials involving 2664 individuals included
• trials were of 12, 24 & 52 weeks duration
• 1.9-2.9 point improvement in cognitive function on ADAS-Cog score with 5-10 mg of donepezil relative to placebo
• 1.7 point improvement in mini mental status examination (MMSE) with 10 mg of donepezil relative to placebo
• significantly more withdrawals from the 10 mg/day group than 5 mg/day or placebo

-> Rogers et al, Neurology 50:136, 1998

• study characteristics
  • 24 week double-blind placebo-controlled trial
  • 208 nursing home patients, mean age 86
• conclusions
  • no discernable improvement in behavior
  • modest benefit on cognition, 1 point on MMSE

-> donepezil for vascular dementia

-> AD2000 study

• Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than cholinesterase inhibitors are needed for Alzheimer's disease.

-> severe Alzheimer's disease

• statistically significant, but modest benefit of uncertain clinical significance

-> ADEAR Press release

• Donepezil May Have Short-Term Benefit for Mild Cognitive Impairment:

See Memory Impairment Study

-> Minimal cognitive impairment

• 27 patients with MCI (minimal cognitive impairment)
• donepezil 10 mg QD vs placebo
• study length 24 weeks

Outcome measures:

• standardized test of delayed recall
• global assessment of function
• numerous secondary endpoints derived from cognitive testing

Results:

• significant difference in two primary outcome measures
• a few small, but statistically significant differences in secondary endpoints favoring the donepezil group
• significantly more drop-outs from the donepezil group 22% vs 8%

-> Vitamin E & Donepezil

• double-blind study
• 769 subjects with amnestic subtype of mild cognitive impairment (MCI)

Groups:

• 2000 IU of vitamin E daily
• 10 mg of donepezil daily
• placebo

Study duration: three years

Primary outcome: clinically possible or probable Alzheimer's disease. Secondary outcomes: cognition & function

Results:

• possible or probable Alzheimer's disease developed in 212 of the 769
• Vitamin E had no benefit in patients with MCI
• donepezil associated with a lower rate of progression to Alzheimer's disease at 12 months, but not at 3 years

-> cholinesterase inhibitor clinical trials (review 2005)

• benefits of cholinesterase inhibitors in Alzheimer disease patients are relatively small & likely extend to only a subset of AD patients that can't be identifed in advance

-> benefit for patients with severe Alzheimer's disease 343 patients, 24 weeks, placebo controlled 5 point improvement on 100 point cogntion scale no benefit in global assessment, ADL or neuropsychiatric behaviors

More general terms

• cholinesterase inhibitor clinical trials

Additional terms

• donepezil (Aricept, Aricept ODT, Adlarity)