Elias Schwam

A Randomized, Double‐Blind, Placebo‐Controlled Study of the Efficacy and Safety of Donepezil in Patients with Alzheimer's Disease in the Nursing Home Setting

OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimers disease (AD) residing in nursing home facilities.

Cholinesterase inhibitors used in the treatment of Alzheimer's disease: The relationship between pharmacological effects and clinical efficacy

The deficiency in cholinergic neurotransmission in Alzheimer’s disease has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease. The clinical benefits of these agents include improvements, stabilisation or less than expected decline in cognition, function and behaviour. The common mechanism of action underlying this class of agents is an increase in available acetylcholine through inhibition of the catabolic enzyme, acetylcholinesterase. There is substantial evidence that the cholinesterase inhibitors, including donepezil, galantamine and rivastigmine, decrease acetylcholines-terase activity in a number of brain regions in patients with Alzheimer’s disease. There is also a significant correlation between acetylcholinesterase inhibition and observed cognitive improvement. However, the cholinesterase inhibitors are reported to have additional pharmacological actions. Rivastigmine inhibits butyrylcholinesterase with a similar affinity to acetylcholinesterase, although it is not clear whether the inhibition of butyrylcholinesterase contributes to the therapeutic effect of rivastigmine.Based on data from preclinical studies, it has been proposed that galantamine also potentiates the action of acetylcholine on nicotinic receptors via allosteric modulation; however, the effects appear to be highly dependent on the concentrations of agonist and galantamine. It is not yet clear whether these concentrations are related to those achieved in the brain of patients with Alzheimer’s disease within therapeutic dose ranges. Preclinical studies have shown that donepezil and galantamine also significantly increase nicotinic receptor density, and increased receptor density may be associated with enhanced synaptic strengthening through long-term potentiation, which is related to cognitive function.Despite these differences in pharmacology, a review of clinical data, including head-to-head studies, has not demonstrated differences in efficacy, although they may have an impact on tolerability. It seems clear that whatever the subsidiary modes of action, clinical evidence supporting acetylcholinesterase inhibition as the mechanism by which cholinesterase inhibitors treat the symptoms of Alzheimer’s disease is accumulating. Certainly, as a class, the currently approved cholinesterase inhibitors (donepezil, galantamine, rivastigmine and tacrine) provide important benefits in patients with Alzheimer’s disease and these drugs offer a significant advance in the management of dementia.

Economic evaluation of donepezil in moderate to severe Alzheimer disease

Objective: To investigate the costs to society of Alzheimer disease (AD) care in a multinational, randomized, placebo-controlled trial of donepezil in patients with moderate to severe AD. Methods: A total of 290 patients with AD (screening standardized Mini-Mental State Examination score 5 to17) were randomized to receive either donepezil (n = 144; 5 mg/day for 28 days, followed by 10 mg/day as per clinician’s judgment) or placebo (n = 146) for 24 weeks. The authors collected data on patient and caregiver health resource utilization prospectively using the Canadian Utilization of Services Tracking questionnaire. Costs were calculated for patients and caregivers in each group based on resource utilization multiplied by the unit prices for each resource. A cost (the average Ontario minimum wage for 1998 [Can

Donepezil treatment in severe Alzheimer's disease: a pooled analysis of three clinical trials

6.85 per hour]) was assigned to unpaid time that caregivers spent assisting the patient with activities of daily living (ADL). Results: Patient and caregiver demographics at baseline were similar across the two groups. After adjusting for baseline total cost per patient, the mean total societal cost per patient for the 24-week period was donepezil, Can

Effectiveness of Donepezil in Reducing Clinical Worsening in Patients with Mild-to-Moderate Alzheimer’s Disease

9,904 (US

Effects of donepezil on activities of daily living: integrated analysis of patient data from studies in mild, moderate and severe Alzheimer's disease

6,686) and placebo, Can

Predicting cognitive decline in Alzheimer's disease: An integrated analysis

10,236 (US

Rates of cognitive change in Alzheimer disease: observations across a decade of placebo-controlled clinical trials with donepezil.

6,910). This net cost saving of Can

Defining treatment response to donepezil in Alzheimer's disease: responder analysis of patient-level data from randomized, placebo-controlled studies.

332 (US

Phase II Crossover Trial of Varenicline in Mild-to-Moderate Alzheimer's Disease

224) included the average 24-week cost of donepezil treatment. Most of the cost-saving with donepezil treatment was due to less use of residential care by patients, and caregivers spending less time assisting patients with ADL. Conclusion: This cost-consequence analysis reveals economic benefits of treatment of moderate to severe AD with donepezil.