Donepezil in Alzheimer’s disease: an evidence-based review of its impact on clinical and economic outcomes

Abstract

Introduction: Donepezil is indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is a specific and reversible inhibitor of acetylcholinesterase (AChE); by increasing levels of available acetylcholine, donepezil may compensate for the loss of functioning cholinergic brain cells. Aims: This review evaluates the clinical impact of donepezil by assessing randomized controlled and open-label naturalistic trials, as well as observational studies. A broad perspective is gained of its effectiveness on various outcomes. Evidence review: There is strong evidence that donepezil has efficacy against the three major domains of Alzheimer's disease symptoms, namely functional ability, behavior, and cognition. The strongest evidence is for improvement or less deterioration in global outcomes and cognition in the short to medium term. There is limited evidence that improved global outcomes are maintained in the long term and clear evidence to support long-term maintenance of cognitive benefits. Also, donepezil appears to maintain function in the long term and there is some level 1 and 2 evidence of improved or limited deterioration in behavior or mood in the short to medium term. Despite donepezil's effects on major symptoms of Alzheimer's disease, its impact on patients' quality of life has not been consistently demonstrated, perhaps reflecting the difficulty of assessing this aspect in this patient population. Donepezil may also lessen caregiver burden. Donepezil has some effect on markers of brain function, but more data are needed to confirm a neuroprotective effect. There is limited and conflicting evidence that long-term donepezil treatment delays time to institutionalization. There is some evidence that donepezil may be cost effective, especially when unpaid caregiver costs are considered. Donepezil is generally safe and well tolerated. Clinical value: AChE inhibitors are the only agents recommended for the treatment of cognitive decline in patients with mild to moderate Alzheimer's disease. Donepezil is more effective than placebo and is well tolerated in improving the major symptoms of this disease. Improvements are usually modest, although stabilization of cognitive and functional symptoms with donepezil can also be considered an important clinical outcome. Donepezil may lessen caregiver burden. Donepezil may also be cost effective, especially when unpaid caregiver costs are considered. More data are required from randomized controlled trials with long-term follow-up to confirm its cost effectiveness and impact on quality of life, disease progression, and time to institutionalization.

Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

“…Although cholinesterase inhibitors have been utilized in treating AD, they specifically target symptom relief in patients and do not hinder the progression of the condition. The use of donepezil results in slight improvements in cognitive function but does not improve the treatment costs, caregiver duties, or length of hospital stays (Knowles, 2006).…”

Carbamate as a potential anti‐Alzheimer's pharmacophore: A review

“…ChEIs are based on the oldest hypothesis of AD and the most common treatment option for mild to moderate AD (Grossberg, 2003). Donepezil (Aricept, 1 ) is an FDA‐approved drug for the treatment of AD, which came into the market in 1996 (Knowles, 2006). Donepezil has been considered a safe and well‐tolerated drug for mild to moderate AD.…”

In Silico Investigation of Novel Compounds as Inhibitors of Acetylcholinesterase Enzyme for the Treatment of Alzheimer’s Diseases

“…Donepezil is used to treat the mild to moderate symptoms of AD where it functions by reversibly inhibiting the cholinergic enzyme, acetylcholinesterase (AChE). Inhibiting AChE prevents it from lysing the neurotransmitter, acetylcholine, thus, allowing the increase of acetylcholine levels in neuromuscular junctions in the brain to occur, thereby, helping to prevent the loss of the cholinergic neurons' function that is experienced in AD patients [ 33 ].…”