Effectiveness of open-label donepezil treatment in patients with Alzheimer's disease discontinuing memantine monotherapy

Sakka, Paraskevi; Tsolaki, Magda; Hort, Jakub; Häger, Klaus; Pousa, Secundino López; Li, Chunming; Schwam, Elias

doi:10.1185/030079907x242773

“…A 12-week, multicenter, open-label study in 103 patients with moderate-to-severe AD focused on switch to donepezil therapy after discontinuation of memantine monotherapy due to poor tolerability or lack of efficacy. 62 The study reported that re-initiation of donepezil treatment in patients with moderate-to-severe AD showed benefits on cognition measuring an approximate increase of 2 points on MMSE, on global assessment of change measured by CGI-I, and in patient social behavior as rated by a caregiver; but no change in behavior was indicated in NPI scores. Forty-two percent of the patients in this study received before study entrance a long-term therapy with AChEI which was discontinued due to lack of efficacy This implies that in clinical settings, a decision for discontinuation of the treatment might have been done prematurely and that realistic evaluation of treatment benefits should include not only improvement and stabilization but also less-than-expected decline.…”

Section: Clinical Efficacymentioning

confidence: 99%

Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

Jelić

¹

,

Darreh‐Shori

²

2010

Clinical Medicine Insights: Therapeutics

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Donepezil is a potent, selective, noncompetitive, and rapidly reversible inhibitor of acetylcholinesterase (AChEI) licensed for the treatment of Alzheimer disease (AD); and is the first and only AChEI licensed for the treatment of severe AD. Its efficacy as monotherapy, or in combination with the NMDA-agonist, memantine, has been documented in several randomised double-blind, placebo-controlled, short-term clinical trials, as well as long-term extension trials and observational studies. Donepezil is a well tolerated drug that is generally safe as demonstrated even in patients with multiple co-morbidities receiving polypharmacy. It has been shown that donepezil improves cognition and global function in patients with mild-to-moderate AD; and long-term efficacy is maintained for up to 50 weeks. There is a dose-response relationship, with higher doses more likely to produce symptomatic benefit. Furthermore, donepeziltreated patients may improve cognitively and show global clinical improvement in all disease stages, including severe AD. Less consistent results in all disease stages were obtained on measures of function and behavior, and observations of mood. No effect on transition to AD has been found in long-term, randomized clinical trials in mild cognitive impairment (MCI). Cost-effectiveness of the treatment has been questioned by one long-term open-label societal study of 2-years duration. This study reported modest improvement of cognition but no statistically significant benefits during donepezil treatment as compared to placebo, in terms of rates of institutionalization and progression toward greater disability. However, there is a need for further research on clinically meaningful outcomes and treatment benefits favored by patients and caregivers, which are traditionally not defined as outcomes in clinical trials. Likewise, we need to know how to select responders, what is an optimal AChE inhibition particularly during the long-term treatment, in which patients the dosage should be increased for a sustained benefit, what is the optimal duration of treatment and when is meaningful to stop the treatment. After almost two decades of donepezil use in everyday clinical practice these issues are still unresolved.

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“…Twelve open-label trials were examined based on our search criteria for this meta-analysis. Five studies examined donepezil; [45][46][47][48][49] three, rivastigmine; 46,50,51 two, galantamine; 46,52 one, memantine; 46 one, gabapentin; 53 one, citalopram; 54 one, methylphenidate; 55 and one, atypical antipsychotic. 56 For these studies, average age ranged from 66 to 83 years.…”

Section: Evidence From Open-label Trialsmentioning

confidence: 99%

Pharmacological Therapy for Apathy in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Sepehry

¹

,

Sarai

²

,

Hsiung

³

2017

Can. J. Neurol. Sci.

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“…A 12-week, multicenter, open-label study in 103 patients with moderate-to-severe AD focused on switch to donepezil therapy after discontinuation of memantine monotherapy due to poor tolerability or lack of efficacy. 62 The study reported that re-initiation of donepezil treatment in patients with moderate-to-severe AD showed benefits on cognition measuring an approximate increase of 2 points on MMSE, on global assessment of change measured by CGI-I, and in patient social behavior as rated by a caregiver; but no change in behavior was indicated in NPI scores. Forty-two percent of the patients in this study received before study entrance a long-term therapy with AChEI which was discontinued due to lack of efficacy.…”

mentioning

confidence: 99%

Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

2017

Clinical Medicine Insights: Geriatrics

0

View full text Add to dashboard Cite

Donepezil is a potent, selective, noncompetitive, and rapidly reversible inhibitor of acetylcholinesterase (AChEI) licensed for the treatment of Alzheimer disease (AD); and is the first and only AChEI licensed for the treatment of severe AD. Its efficacy as monotherapy, or in combination with the NMDA-agonist, memantine, has been documented in several randomised double-blind, placebo-controlled, short-term clinical trials, as well as long-term extension trials and observational studies. Donepezil is a well tolerated drug that is generally safe as demonstrated even in patients with multiple co-morbidities receiving polypharmacy. It has been shown that donepezil improves cognition and global function in patients with mild-to-moderate AD; and long-term efficacy is maintained for up to 50 weeks. There is a dose-response relationship, with higher doses more likely to produce symptomatic benefit. Furthermore, donepeziltreated patients may improve cognitively and show global clinical improvement in all disease stages, including severe AD. Less consistent results in all disease stages were obtained on measures of function and behavior, and observations of mood. No effect on transition to AD has been found in long-term, randomized clinical trials in mild cognitive impairment (MCI). Cost-effectiveness of the treatment has been questioned by one long-term open-label societal study of 2-years duration. This study reported modest improvement of cognition but no statistically significant benefits during donepezil treatment as compared to placebo, in terms of rates of institutionalization and progression toward greater disability. However, there is a need for further research on clinically meaningful outcomes and treatment benefits favored by patients and caregivers, which are traditionally not defined as outcomes in clinical trials. Likewise, we need to know how to select responders, what is an optimal AChE inhibition particularly during the long-term treatment, in which patients the dosage should be increased for a sustained benefit, what is the optimal duration of treatment and when is meaningful to stop the treatment. After almost two decades of donepezil use in everyday clinical practice these issues are still unresolved.

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Effectiveness of open-label donepezil treatment in patients with Alzheimer's disease discontinuing memantine monotherapy

Abstract: Donepezil was effective and well tolerated in moderate-to-severe AD patients who discontinued memantine monotherapy, including those with previous exposure to ChE inhibitors.

Cited by 5 publications

References 30 publications

Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

Pharmacological Therapy for Apathy in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

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