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Meta-Analysis
. 2023 Nov;40(11):953-964.
doi: 10.1007/s40266-023-01065-x. Epub 2023 Sep 8.

Psychiatric Adverse Events of Acetylcholinesterase Inhibitors in Alzheimer's Disease and Parkinson's Dementia: Systematic Review and Meta-Analysis

Nadine Bittner  1 , Cleo S M Funk  2 , Alexander Schmidt  3 , Felix Bermpohl  4 , Eva J Brandl  4 , Engi E A Algharably  2 , Reinhold Kreutz  2 , Thomas G Riemer  5   6
Affiliations
Meta-Analysis

Psychiatric Adverse Events of Acetylcholinesterase Inhibitors in Alzheimer's Disease and Parkinson's Dementia: Systematic Review and Meta-Analysis

Nadine Bittner et al. Drugs Aging. 2023 Nov.

Abstract

Background: The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia.

Objectives: While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined.

Methods: We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia.

Results: A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine.

Conclusions: Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia.

Clinical trial registration: The study was pre-registered on PROSPERO (CRD42021258376).

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Conflict of interest statement

Reinhold Kreutz reports modest honoraria for consultancy and lectures and support for research from Bayer AG, CinCor Menarini, Merck, Sanofi, and Servier outside the submitted work. Eva J. Brandl has received speaker fees from Medice. Nadine Bittner, Cleo S.M. Funk, Alexander Schmidt, Felix Bermpohl, Engi E.A. Algharably, and Thomas G. Riemer have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Study selection flowchart. Results of the database and trial registry search. AChEI acetylcholinesterase inhibitor, AEs adverse events, PAEs psychiatric adverse events
Fig. 2
Fig. 2
Forest plot for acetylcholinesterase inhibitors (AChEIs) versus placebo. CI confidence interval, DON donepezil, GAL galantamine, M-H Mantel-Haenszel, RIV rivastigmine
See this image and copyright information in PMC

Comment in

  • So schlagen Antidementiva auf die Psyche.
    Metzger F. Metzger F. MMW Fortschr Med. 2024 Mar;166(5):34. doi: 10.1007/s15006-024-3742-5. MMW Fortschr Med. 2024. PMID: 38514549 Review. German. No abstract available.
  • FEV1 kann voraussagen, wie Raucher sterben.
    Melzer T, Kahnert K. Melzer T, et al. MMW Fortschr Med. 2024 Mar;166(5):34-35. doi: 10.1007/s15006-024-3740-7. MMW Fortschr Med. 2024. PMID: 38514550 Review. German. No abstract available.

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