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Clinical Interventions in Aging 2018Donepezil, an acetylcholinesterase inhibitor (AChEI), has been widely used to treat Alzheimer's disease (AD) in China. However, there are few studies focusing on the... (Comparative Study)
Comparative Study Review
Donepezil, an acetylcholinesterase inhibitor (AChEI), has been widely used to treat Alzheimer's disease (AD) in China. However, there are few studies focusing on the efficacy and safety of donepezil in Chinese patients. In this review, we discuss 1) the efficacy of donepezil and its comparison with other AChEIs or memantine, 2) the therapeutic responses to donepezil and its influencing factors, and 3) the safety and tolerability of donepezil in Chinese patients with different stages of AD and amnestic mild cognitive impairment, and further compare the similarities and differences of the results between Chinese studies and previous Western studies that predominantly enrolled Caucasian subjects. We include Chinese clinical trials and other well-designed studies investigating donepezil or using donepezil as a positive control, in which the efficacy and/or safety of donepezil have been analyzed. Based on these studies, donepezil has been shown to be effective and safe in Chinese AD patients and may impact AD biomarkers, such as hippocampal atrophy, Aβ, and tau. In addition, the therapeutic response to donepezil may be influenced by apolipoprotein E or cytochrome P450 2D6 polymorphism.
Topics: Alzheimer Disease; China; Cholinesterase Inhibitors; Cognitive Dysfunction; Donepezil; Humans; Memantine; Severity of Illness Index
PubMed: 30349215
DOI: 10.2147/CIA.S159920 -
Brain and Behavior Nov 2020Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and donepezil are frequently used in its treatment, both as monotherapy and in combination. This multiple treatment comparison meta-analysis assessed the efficacy of these regimens and placebo in the management of AD.
METHODS
We searched PubMed, Embase, the Cochrane Library, and Wanfang Med Online and China National Knowledge Infrastructure for English and Chinese publications from the first records to 17 April 2020. Two investigators scanned articles for placebo-controlled trials of memantine and donepezil alone and in combination. We extracted data on the following outcomes: cognition, global assessment, daily activities, neuropsychiatric symptoms, adverse events, and the acceptability and cost of these treatment regimens.
RESULTS
Of 936 records screened, we included 54 trials in this analysis. The combination therapy was more effective in improving cognition (mean difference (MD)-5.01, 95% credible interval (95% Crl) -10.73 to 0.86 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale; MD 9.61, 95% Crl 2.29 to 16.97 in the Severe Impairment Battery), global assessment (MD -2.88, 95% Crl -6.04 to 0.40), daily activities (MD 13.06, 95% Crl -34.04 to 58.92), and neuropsychiatric symptoms (MD -6.84, 95% Crl -10.62 to -2.82) compared with placebo. Memantine was more acceptable than placebo (MD 0.93, 95% Crl 0.69 to 1.22).
CONCLUSIONS
Memantine plus donepezil showed superior outcomes for cognition, global assessment, daily activities, and neuropsychiatric symptoms, but lower acceptability than monotherapy and placebo. Combination therapy may be more cost-effective, because memantine slows the progression of AD.
Topics: Alzheimer Disease; China; Donepezil; Humans; Memantine; Network Meta-Analysis
PubMed: 32914577
DOI: 10.1002/brb3.1831 -
The Senior Care Pharmacist Jul 2023Prevalence of dementia continues to increase with limited pharmacotherapy options available. Acetylcholinesterase inhibitors remain a mainstay of treatment. The US FDA... (Review)
Review
Prevalence of dementia continues to increase with limited pharmacotherapy options available. Acetylcholinesterase inhibitors remain a mainstay of treatment. The US FDA has approved three oral medications within this class- donepezil, galantamine, and rivastigmine. In 2022, the US Food and Drug Administration approved a novel patch formulation for donepezil that could be beneficial for patients with dysphagia as well as potentially decreasing the side effect burden. The purpose of this analysis is to review the efficacy, safety, tolerability, and clinical considerations related to this novel formulation.
Topics: Humans; Acetylcholinesterase; Donepezil; Drug-Related Side Effects and Adverse Reactions; Rivastigmine; United States; United States Food and Drug Administration
PubMed: 37381137
DOI: 10.4140/TCP.n.2023.300 -
British Journal of Community Nursing Mar 2020
Review
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Male; Treatment Outcome
PubMed: 32160022
DOI: 10.12968/bjcn.2020.25.3.148 -
Cognitive and Behavioral Neurology :... Dec 2021Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the treatment of moderate AD.
OBJECTIVE
To evaluate the effects of donepezil and memantine in relieving BPSD in individuals with moderate AD.
METHOD
We conducted a prospective, randomized, 6-month clinical trial involving 85 individuals with moderate AD divided into two groups: group 1 (n = 42) was treated with donepezil; group 2 (n = 43) was treated with memantine. We used the Neuropsychiatric Inventory (NPI) to assess the prevalence and severity of BPSD at baseline and after 6 months of treatment with donepezil or memantine.
RESULTS
The two groups' baseline characteristics, including age, sex, mean length of education, and disease duration, were comparable, as were their baseline Mini-Mental State Examination scores. The NPI Total score improved from baseline to month 6 in both groups (P < 0.0001). Analyses of the NPI subdomains revealed that both donepezil treatment and memantine treatment produced statistically significant improvement in all of the NPI domains except euphoria and apathy, for which no improvement was observed after memantine treatment. Both treatments were well tolerated, with mostly mild and transient adverse effects.
CONCLUSION
Specific drugs for AD, including donepezil and memantine, may be effective in treating BPSD in individuals with moderate AD, with a favorable safety profile.
Topics: Alzheimer Disease; Behavioral Symptoms; Donepezil; Humans; Indans; Memantine; Piperidines; Prospective Studies; Treatment Outcome
PubMed: 34851866
DOI: 10.1097/WNN.0000000000000285 -
ACS Chemical Neuroscience Jan 2019The discovery of acetylcholine and acetylcholinesterase provided the first insight into the intricacies of chemical signal transduction and neuronal communication.... (Review)
Review
The discovery of acetylcholine and acetylcholinesterase provided the first insight into the intricacies of chemical signal transduction and neuronal communication. Further elucidation of the underlying mechanisms led to an attendant leveraging of this knowledge via the synthesis of new therapeutics designed to control aberrant biochemical processes. The central role of the cholinergic system within human memory and learning, as well as its implication in Alzheimer's disease, has made it a point of focus within the neuropharmacology and medicinal chemistry communities. This review is focused on donepezil and covers the background, synthetic routes, structure-activity relationships, binding interactions with acetylcholinesterase, pharmacokinetics and metabolism, efficacy, adverse effects, and historical importance of this leading therapeutic in the treatment of Alzheimer's disease and true Classic in Chemical Neuroscience.
Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Cholinesterase Inhibitors; Donepezil; Humans; Nerve Degeneration; Structure-Activity Relationship
PubMed: 30372021
DOI: 10.1021/acschemneuro.8b00517 -
Life Sciences Dec 2020Ischemic stroke remains the leading cause of morbidity and the second most common cause of mortality worldwide. Over the past decade, endovascular thrombectomy (EVT)... (Review)
Review
Ischemic stroke remains the leading cause of morbidity and the second most common cause of mortality worldwide. Over the past decade, endovascular thrombectomy (EVT) drastically changed the care of patients with ischemic stroke due to large vessel occlusion. Nevertheless, despite revascularization, many patients do not achieve a good functional outcome. Moreover, not all patients with ischemic stroke are eligible for EVT. During ischemia, a cascade of ischemic and inflammatory changes lead to permanent damage. As such, adjunct therapies that can protect neurons during acute ischemic phase prior to revascularization have the potential of enhancing functional recovery. Donepezil, an acetylcholinesterase inhibitor, improves cognition and global function in patients with Alzheimer's and Vascular dementia via modulation of acetylcholine receptors and downstream inflammatory response. Preclinical studies demonstrated the potential neuroprotective effects of donepezil in ischemic stroke. However, only a handful of clinical studies investigated this drug's safety and efficacy in stroke patients. In this review, we summarize the current evidence for the utility, or lack thereof, donepezil in treating and rehabilitating patients with ischemic stroke.
Topics: Animals; Cholinesterase Inhibitors; Donepezil; Humans; Ischemic Stroke; Neuroprotective Agents; Recovery of Function
PubMed: 33058916
DOI: 10.1016/j.lfs.2020.118575 -
Journal of Forensic and Legal Medicine Jan 2024Donepezil is one of the primary treatments options for patients suffering from Alzheimer's Disease. In a review of more than 2200 postmortem donepezil positive blood... (Review)
Review
Donepezil is one of the primary treatments options for patients suffering from Alzheimer's Disease. In a review of more than 2200 postmortem donepezil positive blood specimens, 76% of concentrations were higher than the proposed therapeutic range. Means and medians were similar between central blood specimens and peripheral specimens, indicating minimal postmortem redistribution. Postmortem concentrations may not reflect those circulating antemortem. Mean and median postmortem blood concentrations were approximately 3-fold higher than those in antemortem blood specimens. Additionally, in cases where antemortem blood was available for testing, large increases in donepezil concentrations were reported between antemortem and postmortem specimens without documented administration by medical personnel. Elevated blood donepezil concentrations have been reported in multiple postmortem cases where cause of death was unrelated. The blood concentrations reported in cases where donepezil did not contribute to death overlapped with those in suspected drug overdose cases where other drugs may have been present. In 4 out of 5 suspected donepezil overdose cases, blood concentrations greater than 1000 ng/mL were reported, whereas less than 1% of all postmortem blood samples reviewed achieved these concentrations. Blood concentrations greater than 1000 ng/mL should be considered contributory when a drug overdose is suspected. Postmortem donepezil concentrations should be interpreted with caution in the context of a comprehensive case history.
Topics: Humans; Donepezil; Postmortem Changes; Autopsy; Drug Overdose
PubMed: 38043240
DOI: 10.1016/j.jflm.2023.102625 -
Neuropharmacology Jun 2021Alzheimer's disease (AD), the most common cause of adult-onset dementia is characterized by a progressive decline of cognitive functions accompanied by behavioral... (Review)
Review
Alzheimer's disease (AD), the most common cause of adult-onset dementia is characterized by a progressive decline of cognitive functions accompanied by behavioral manifestations. The main class of drugs currently used for the treatment of AD are acetylcholinesterase/cholinesterase inhibitors (ChE-Is). The first ChE-I licensed for symptomatic treatment of AD was tacrine. The ChE-Is currently available in the market are donepezil, rivastigmine and galantamine as tacrine is no longer in use, due to its hepatotoxicity. According to mechanism of action the ChE-Is are classified as short-acting or reversible agents such as tacrine, donepezil, and galantamine, as intermediate-acting or pseudo-irreversible agent such as rivastigmine. Overall, the efficacy of the three ChE-Is available in the market is similar and the benefit of administration of these compounds is mild and may not be clinically significant. Due to gastrointestinal side effects of these drugs, medicinal chemistry and pharmaceutical delivery studies have investigated solutions to improve the pharmacological activity of these compounds. In spite of the limited activity of ChE-Is, waiting for more effective approaches, these drugs still represent a pharmacotherapeutic resource for the treatment of AD. Other approaches in which ChE-Is were investigated is in their use in combination with other classes of drugs such as cholinergic precursors, N-methyl-d-aspartate (NMDA) receptor antagonists and antioxidant agents. After many years from the introduction in therapy of ChE-Is, the combination with other classes of drugs may represent the chance for a renewed interest of ChE-Is in the treatment of adult-onset dementia disorders.
Topics: Alzheimer Disease; Antioxidants; Cholinesterase Inhibitors; Donepezil; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Galantamine; Humans; Receptors, N-Methyl-D-Aspartate; Rivastigmine
PubMed: 33035532
DOI: 10.1016/j.neuropharm.2020.108352 -
Molecular Pharmaceutics Jul 2021Dementia is a significant public health problem in the 21st century. Alzheimer's disease (AD) is an essential factor in dementia. Currently, the drugs used for the... (Review)
Review
Dementia is a significant public health problem in the 21st century. Alzheimer's disease (AD) is an essential factor in dementia. Currently, the drugs used for the treatment of AD are mainly acetylcholine inhibitors (AChEIs). As an AChEI, donepezil (DP) can improve patients' cognitive ability with low side effects and has been accepted by most patients and doctors. For AD patients, the dosage regimen is also crucial due to aging and diseases. Although there are DP oral tablets on the market, there are still many problems to be solved. At present, more and more research is conducted to optimize the route of administration of DP to improve the self-administration of patients. The research fields of DP administration include oral administration, injection administration, intranasal administration, and transdermal administration. This Review is to present the development of different DP administrations and evaluates the advantages and limitations of those works, hoping to optimize the DP dosage regimen for AD patients.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Drug Administration Routes; Drug Delivery Systems; Humans
PubMed: 34100291
DOI: 10.1021/acs.molpharmaceut.1c00290