Extemporaneous combination of donepezil and memantine to treat dementia in Alzheimer disease: evidence from Italian real-world data

Padovani, Alessandro; Falato, Serena; Pégoraro, V.

doi:10.1080/03007995.2023.2182530

Cited by 5 publications

(2 citation statements)

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“…Experiments have consistently demonstrated that treatment with memantine leads to a reduction in both the volume and extent of neuronal damage, suggesting its potential neuroprotective properties. The effectiveness of memantine has been observed in various experimental models, including cerebral infarction (Görgülü et al, 2000), hemorrhage, chronic ischemia, traumatic injury (Padovani et al, 2023;Thakral et al, 2023), in cortical culture neurons (Lopes et al, 2013), granular cells of the cerebellum (Volbracht et al, 2006) and retinal ganglion cells (Hassan et al, 2022). Under the conditions of our experimental model after co-incubation of hippocampal neurons with NMDA and memantine the number of living cells increased, and the number of apoptotic and necrotic cells decreased compared to the values obtained with the isolated addition of NMDA alone, approaching to the control values.…”

Section: Discussionmentioning

confidence: 99%

Memantine protects the cultured rat hippocampal neurons treated by NMDA and amyloid β1–42

Rozumna,

Hanzha,

Lukyanetz

2023

Front. Neurosci.

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Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no effective treatments. Recent research highlights the role of NMDA receptors in AD development, as excessive activation of these receptors triggers excitotoxicity. Memantine, an NMDA receptor antagonist, shows promise in curbing excitotoxicity. What sets our study apart is our novel exploration of memantine’s potential to protect hippocampal neurons from neurotoxicity induced by NMDA and amyloid β1–42, a hallmark of AD. To achieve this, we conducted a series of experiments using rat hippocampal cell cultures. We employed Hoechst and propidium iodide double staining to assess neuronal viability. Analyzing the viability of neurons in normal conditions compared to their status after 24 h of exposure to the respective agents revealed compelling results. The incubation of hippocampal neurons with NMDA or amyloid β1–42 led to a more than twofold increase in the number of apoptotic and necrotic neurons. However, when memantine was co-administered with NMDA or amyloid β1–42, we witnessed a notable augmentation in the number of viable cells. This unique approach not only suggests that memantine may act as a neuroprotective agent but also emphasizes the relevance of hippocampal neuron cultures as valuable models for investigating excitotoxicity and potential AD treatments.

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Section: Discussionmentioning

confidence: 99%

Memantine protects the cultured rat hippocampal neurons treated by NMDA and amyloid β1–42

Rozumna,

Hanzha,

Lukyanetz

2023

Front. Neurosci.

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“…In contrast, memantine is a noncompetitive NMDA receptor antagonist that prevents NMDA overactivation and glutamate-mediated neurotoxicity, thereby protecting neuronal cells ( Chayrov et al, 2022 ; Turcu et al, 2022 ). Basic research and clinical studies have shown that the combination of donepezil and memantine can address both pathologies and achieve therapeutic complementarity, resulting in more significant and cost-effective improvements in cognition and overall clinical status than either donepezil or memantine monotherapy ( Yabuki et al, 2017 ; Guo et al, 2020 ; Padovani et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Yang,

Wei,

Tian

et al. 2024

Front. Pharmacol.

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BackgroundDonepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy.MethodsWe retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age.ResultsOf the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment.ConclusionOur study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

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Acute treatment of migraine: quantifying the unmet need through real-world data in Italy

Sacco,

Di Ciaccio,

Di Virgilio

et al. 2024

Neurol Sci

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Objective This study is describing subjects with migraine interrupting or not receiving triptans for acute treatment and providing a national-level estimate of people who might benefit from different therapeutic approaches. Methods This is a retrospective analysis using IQVIA Longitudinal Patient Database. Starting from 18 + years old individuals with migraine, we selected two cohorts: subjects with triptans prescriptions before and no triptans prescriptions after Index Date (triptan withdraw) and subjects without triptans prescriptions both before and after Index Date (no triptan prescriptions). Index Date was the first record of a health encounter for migraine in 2019. Individuals with cardiovascular disease (CVD) within no triptan prescriptions group were also quantified. Results Triptan withdraw and no triptan prescriptions cohorts numbered 605 and 3270, respectively, 5% and 29% of subjects with migraine. Mean age was 47 and 51 years respectively; women were more represented (~ 80%). Hypertension and thyroid disease were most frequent comorbidities; non-steroidal anti-inflammatory drugs were among most frequently recorded treatments. Subjects with CVD within no triptan prescriptions cohort were 621 and with triptan withdraw cohort subjects represented the basis to estimate those who might benefit from alternative options for the acute treatment of migraine, who were around 60,000 and accounted for 11% of subjects seeking primary care due to migraine. Conclusions This analysis provides a real-word estimate of Italian people that might benefit from different therapeutic approaches as an alternative to triptans, which sometimes might be not effective and/or poorly tolerated. Such estimate should be intended as the lower limit of a wider range due to strict criteria adopted.

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Extemporaneous combination of donepezil and memantine to treat dementia in Alzheimer disease: evidence from Italian real-world data

Cited by 5 publications

References 50 publications

Memantine protects the cultured rat hippocampal neurons treated by NMDA and amyloid β1–42

Memantine protects the cultured rat hippocampal neurons treated by NMDA and amyloid β1–42

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Acute treatment of migraine: quantifying the unmet need through real-world data in Italy

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