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Cited by 397Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 94 of the 101 references it cites were found in a registry or an index.

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Open access
Grossberg, George T·2003·Current Therapeutic Research
DOI 10.1016/s0011-393x(03)00059-6PMC PMC4052996
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Abstract

Background Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.Results All ChE inhibitors have the potential to induce centrally mediated cholinergic adverse events (AEs), such as nausea and vomiting, if the dose is increased too rapidly or in increments that are too large. These AEs, which are most likely to occur during the "getting on," or dose-escalation, phase of treatment, may result in patients discontinuing treatment early without achieving optimum therapeutic benefit. To reduce the incidence of these AEs, a slow dose-escalation schedule has been established in clinical practice, consisting of a "start low, go slow" procedure with a minimum of 4 weeks between dose increases. After "getting on" treatment, maintaining treatment in the long term, or "staying on," may be achieved with good safety, tolerability, and sustained symptomatic efficacy across the key symptom domains (activities of daily living, behavior, and cognition).Conclusions ChE inhibitors provide symptomatic benefit in AD across key symptom domains. Factors influencing the safety, tolerability, and efficacy of these agents in clinical practice include ChE enzymes inhibited, brain and brain-region ChE selectivity, and metabolism route. Class-specific cholinergic AEs can be minimized using slow, flexible dose escalation.

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Show all 101 references

Research works printed but not linked: 10

  1. McRae, 1999, A large-scale, open-label trial of donepezil in the treatment of Alzheimer's disease: Side effects and concomitant medication use, Int J Neuropharmacol, 2, S176
  2. Shua-Haim, 2001, Safety and tolerability of slow titration of rivastigmine (Exelon) in the treatment of patients with Alzheimer's disease (AD): An overall analysis of two prospective studies, J Am Geriatr Soc, 49, S76
  3. Vellas, 1998, Interim results from an international clinical trial with rivastigmine evaluating a 2-week titration rate in mild to severe Alzheimer's disease patients, Int J Geriatr Psychopharmacol, 1, 140
  4. Schneider, 1998, Systematic review of efficacy of rivastigmine for patients with Alzheimer's disease, Int J Geriatr Psychopharmacol, 1, S26
  5. Anand, 2000, Dose-response effect of rivastigmine in the treatment of Alzheimer's disease, Int J Geriatr Psychopharmacol, 2, 68
  6. Cummings, 2000, Rivastigmine provides behavioural benefits to Alzheimer's disease patients residing in a nursing home: Findings from a 26-week trial, Neurology, 54, A468
  7. Sanders, 2001, Donepezil in dementia with Lewy bodies: Treatment and withdrawal, Int Psychogeriatr, 13, 224
  8. Raskind M, Truyen L. Galantamine has long-term cognitive benefits in Alzheimer's disease—an analysis of responder rates at 36 months. Poster presented at the 7th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy; April 3–6, 2003; Geneva, Switzerland.
  9. Grossberg, 2001, Rivastigmine in Alzheimer's disease: Efficacy over 2 years compared with historical controls, Int Psychogeriatr, 13, 237
  10. Barber, 1996, Butyrylcholinesterase alters the aggregation state of Aβ amyloid, Proc Soc Neurosci, 22, 1172

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Metadata

Authors
Grossberg, G. T.
Affiliations
Saint Louis University (US)
Corresponding author
Grossberg, George T
ORCID
Grossberg, George T
Venue
Current Therapeutic Research
Publisher
Elsevier BV
Published
2003-04
Volume
64
Issue
4
Pages
216-235
ISSN
0011-393X (ISSN-L)
DOI
10.1016/s0011-393x(03)00059-6
PMC
PMC4052996
OpenAlex
W170237590
Cited by
384
References
101
Citations by year
2026: 26 · 2025: 45 · 2024: 72 · 2023: 41 · 2022: 28 · 2021: 27 · 2020: 20 · 2019: 24 · 2018: 19 · 2017: 14 · 2016: 11 · 2015: 7 · 2014: 3 · 2013: 7 · 2012: 5
FWCI
3.00
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Current Therapeutic Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Novartis Pharma
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
cholinesterase inhibitors, Alzheimer's disease, donepezil, galantamine, rivastigmine, acetylcholinesterase inhibitors, butyrylcholinesterase inhibitors, dose escalation, safety and tolerability

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