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Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review

IMPORTANCE: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear. OBJECTIVE: To assess...

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Autores principales: Knorz, Adrian L., Quante, Arnim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210120/
https://www.ncbi.nlm.nih.gov/pubmed/34476990
http://dx.doi.org/10.1177/08919887211044746
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author Knorz, Adrian L.
Quante, Arnim
author_facet Knorz, Adrian L.
Quante, Arnim
author_sort Knorz, Adrian L.
collection PubMed
description IMPORTANCE: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear. OBJECTIVE: To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy. METHODS: The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020. RESULTS: Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on Gingko biloba in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research. CONCLUSION: Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.
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spelling pubmed-92101202022-06-22 Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review Knorz, Adrian L. Quante, Arnim J Geriatr Psychiatry Neurol Reviews IMPORTANCE: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear. OBJECTIVE: To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy. METHODS: The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020. RESULTS: Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on Gingko biloba in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research. CONCLUSION: Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated. SAGE Publications 2021-09-03 2022-07 /pmc/articles/PMC9210120/ /pubmed/34476990 http://dx.doi.org/10.1177/08919887211044746 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Reviews
Knorz, Adrian L.
Quante, Arnim
Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
title Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
title_full Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
title_fullStr Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
title_full_unstemmed Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
title_short Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
title_sort alzheimer’s disease: efficacy of mono- and combination therapy. a systematic review
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210120/
https://www.ncbi.nlm.nih.gov/pubmed/34476990
http://dx.doi.org/10.1177/08919887211044746
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