Safety and Effectiveness of Donepezil on Behavioral Symptoms in Patients With Alzheimer Disease

Abstract

The objective of this study was to evaluate the prevalence and treatment responsiveness of neuropsychiatric symptoms in patients with mild to moderately severe Alzheimer disease recruited in a naturalistic treatment setting in Spain. All the patients, who matched the prescribing recommendations for donepezil and were able to participate in the study, received donepezil (5 to 10 mg/d) for 6 months. The primary outcome measure was the incidence of adverse events. Secondary outcome measures were neuropsychiatric function measured by the Neuropsychiatric Inventory (NPI), the Mini-Mental State Evaluation, and caregiver burden measured by the Zarit scale. Five hundred and twenty-nine patients were included of which 455 completed the study. The mean baseline NPI score was 19.1. Sixty-five patients (12.3%) experienced an adverse event. The most frequent adverse events were diarrhea and agitation (<2%). Seventeen patients (3%) presented with a neuropsychiatric adverse event and 11 (2%) patients presented with a neurologic adverse event over the course of the study. NPI scores improved by 34.4% over the course of the study, with all items showing a statistically significant improvement. Mini-Mental State Evaluation scores and Zarit caregiver burden scores also improved by 1.27 points and 5.9 points, respectively. This study showed a low incidence of adverse events accompanied by an improvement in the neuropsychiatric and cognitive functions in patients with mild to moderately severe Alzheimer disease treated with donepezil in a community setting in Spain. Donepezil also reduced caregiver burden.

Efficacy of Memantine, Donepezil, or Their Association in Moderate‐Severe Alzheimer’s Disease: A Review of Clinical Trials

“…Carrasco et al [23]: 455 participants recruited from 72 centers from Spain, assessed for 24 weeks, mean age 74 years, mean baseline MMSE 16 (moderate) and 11 (severe). Concomitant medications excluded were anticholinergic drugs, cholinergic agonists, neuromuscular blocking agents, and beta blockers.…”

“…The first unambiguous demonstration of donepezil's beneficial impact on behavioral symptoms in patients with the moderate-severe stage was provided by Carrasco and coworkers [23]. The main effects included the improvement of neuropsychiatric and cognitive functions and the reduction of caregiver burden.…”

“…On assessing the results of monotherapy treatment of moderate-severe AD patients, RCTs reviewed indicate that both memantine and donepezil show benefits. These benefits are in cognitive [18, 20, 21, 27, 28] and global outcomes [20, 26] and in behavioral symptoms [19, 22, 23]. …”

“…Memantine was found to improve global cognition [18, 20, 21], functional communication [20], and some behavioral symptoms (agitation and aggression) [19, 22]. Donepezil at 10 mg/day improved the neuropsychiatric [23], cognitive [23, 26–28], and global functions [26–28], reducing therefore the caregiver burden [23]. Donepezil at 23 mg/day was found to be safe and tolerated in patients with moderate-to-severe AD [24, 25], but further studies are necessary for confirming its suitability in the severe stage of the disease.…”

The effect of electroacupuncture combined with donepezil on cognitive function in Alzheimer’s disease patients: study protocol for a randomized controlled trial

“…Moreover, as the MTA-scale scores differentiate between moderate to severe AD patients with a sensitivity of 70–100% and a specificity of 67–96%, according to the severity of the condition of participants, subgroup analysis will be applied in the statistical analysis. Furthermore, donepezil is approved by the FDA to treat the symptoms of mild to moderate AD [24, 25] and studies have shown that it can improve the neuropsychiatric, cognitive, and global functions [32–34]. Accordingly, donepezil was chosen as a positive control in this trial.…”