People with dementia due to Alzheimer’s disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in activities of daily living, cognitive function, and clinician-rated global clinical state, according to a systematic review in Cochrane Database of Systematic Reviews.
Jacqueline S. Birks, University of Oxford, Oxford, UK and Richard J. Harvey, Deakin University, Geelong, Australia, conducted the study to assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer’s disease; to compare the efficacy and safety of different doses of donepezil; and to assess the effect of donepezil on healthcare resource use and costs.
Alzheimer’s disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer’s disease is to enhance cholinergic neurotransmission in the brain by blocking the action of the enzyme responsible for the breakdown of the neurotransmitter acetylcholine. This can be done by a group of drugs known as cholinesterase inhibitors. Donepezil is a cholinesterase inhibitor.
For the study, the researchers searched Cochrane Dementia and Cognitive Improvement’s Specialized Register, MEDLINE, Embase, PsycINFO and a number of other sources on 20 May 2017.
They included all double-blind, randomized controlled trials in which treatment with donepezil was administered to people with mild, moderate or severe dementia due to Alzheimer’s disease for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two different doses of donepezil were compared.
Thirty studies involving 8257 participants met the inclusion criteria of the review, of which 28 studies reported results in sufficient detail for the meta-analyses. Most studies were of six months’ duration or less. Only one small trial lasted 52 weeks. The studies tested mainly donepezil capsules at a dose of 5 mg/day or 10 mg/day.
- After 26 weeks of treatment, donepezil compared with placebo was associated with better outcomes for cognitive function measured with the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog, range 0 to 70), the Mini-Mental State Examination (MMSE) score and the Severe Impairment Battery (SIB, range 0 to 100).
- Donepezil was also associated with better function measured with the Alzheimer’s Disease Cooperative Study activities of a daily living score for severe Alzheimer’s disease.
- A higher proportion of participants treated with donepezil experienced improvement on the clinician-rated global impression of change scale.
- There was no difference between donepezil and placebo for behavioral symptoms measured by the Neuropsychiatric Inventory (NPI) or by the Behavioural Pathology in Alzheimer’s Disease (BEHAVE-AD) scale.
- There was also no difference between donepezil and placebo for Quality of Life (QoL).
- Participants receiving donepezil were more likely to withdraw from the studies before the end of treatment or to experience an adverse event during the studies.
- There was no evidence of a difference between donepezil and placebo for patient total healthcare resource utilization.
- The 5 mg dose was associated with a slightly worse cognitive function on the ADAS-Cog, but not on the MMSE or SIB, with slightly better QoL and with fewer adverse events and withdrawals from treatment.
- There were no differences on efficacy outcomes, but fewer participants on 10 mg/day experienced adverse events or withdrew from treatment.
“There is moderate-quality evidence that people with mild, moderate or severe dementia due to Alzheimer’s disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function, activities of daily living and clinician-rated global clinical state,” write the authors. “There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total healthcare resource costs. Benefits on 23 mg/day were no greater than on 10 mg/day, and benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose, but the rates of withdrawal and of adverse events before the end of treatment were higher the higher the dose.”
For more information click on the link: 10.1002/14651858.CD001190.pub3