CoChat
Sign Up
Cited by 141Urinary Bladder and Prostate ResearchPharmaceutical Practices and Patient OutcomesUrinary Tract Infections Management

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin: Cognitive function for patients with OAB

Open access
Kay, G. G., Ebinger, U.·2008·International Journal of Clinical Practice
DOI 10.1111/j.1742-1241.2008.01849.xPMC PMC2734922
Open this paper in CoChat — free account

Abstract

BACKGROUND: Antimuscarinic agents used in the treatment of overactive bladder (OAB) differ in their potential to impair cognitive function. It is hypothesised that low brain concentrations and relatively low selectivity for the M(1) muscarinic receptor may reduce the potential for adverse central nervous system (CNS) effects with darifenacin, compared with other antimuscarinics, particularly oxybutynin. METHODS: Cognitive function studies evaluating darifenacin, oxybutynin, tolterodine, solifenacin and/or trospium were identified from publications databases (Medline, Biosis and Embase) and congress abstracts. Preclinical studies and randomised controlled trials in adults were reviewed. RESULTS: Five randomised, double-blind, multiple-dose studies of cognitive function were identified. Oxybutynin was consistently associated with cognitive deficit (four studies), whereas darifenacin did not impair cognition (three studies). These findings were supported by data from sleep/attention and EEG studies. Tolterodine data were limited to one small study with each formulation. For solifenacin and trospium, there were no human studies evaluating memory, the cognitive function most vulnerable to CNS anticholinergics. CONCLUSIONS: There is compelling evidence of cognitive impairment with oxybutynin, whereas darifenacin stands out by demonstrating no impairment of memory or other cognitive functions in three randomised, controlled trials. This may be attributed to the differences in physicochemical properties, efflux mechanisms and relative M(1) muscarinic receptor sparing. The risk of CNS impairment is of particular concern for vulnerable populations such as the elderly (a substantial proportion of the OAB population), and CNS-compromised neurogenic bladder patients such as those with multiple sclerosis or Parkinson's disease.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1742-1241.2008.01849.x

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Anticholinergic urological drugs, particularly oxybutynin, have been consistently associated with short term cognitive decline in randomised controlled trials.

    “Anticholinergic urological drugs, particularly oxybutynin, have been consistently associated with short term cognitive decline in randomised controlled trials,8 41 so a long term risk of dementia is plausible.”

    From Anticholinergic drugs and risk of dementia: case-control study (2018) · cites this paper as [41]

    The section on double-blind clinical studies reports that oxybutynin was consistently associated with cognitive deterioration in four randomised studies. The Summary and conclusions distinguishes it from other overactive-bladder antimuscarinics: darifenacin and tolterodine did not show cognitive decline in the studies reviewed. The evidence therefore supports the claim for oxybutynin, but not its broad wording about anticholinergic urological drugs as a group. The sentence presents long-term dementia risk as the citing authors’ inference, not as a finding attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 54

  1. Irwin, 2006, Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study, Eur Urol, 50, 1306, 10.1016/j.eururo.2006.09.019 · DOI
  2. Ouslander, 2004, Management of overactive bladder, N Engl J Med, 350, 786, 10.1056/NEJMra032662 · DOI
  3. Chess-Williams, 2001, The minor population of M3 receptors mediate contraction of human detrusor muscle in vitro, J Auton Pharmacol, 21, 243, 10.1046/j.1365-2680.2001.00231.x · DOI
  4. Stevens, 2007, Human idiopathic and neurogenic overactive bladders and the role of M2 muscarinic receptors in contraction, Eur Urol, 52, 531, 10.1016/j.eururo.2006.11.016 · DOI
  5. Abrams, 2006, Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder, Br J Pharmacol, 148, 565, 10.1038/sj.bjp.0706780 · DOI
  6. Milsom, 2001, How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study, BJU Int, 87, 760, 10.1046/j.1464-410x.2001.02228.x · DOI
  7. Stewart, 2003, Prevalence and burden of overactive bladder in the United States, World J Urol, 20, 327, 10.1007/s00345-002-0301-4 · DOI
  8. Kay, 2005, Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients, J Am Geriatr Soc, 53, 2195, 10.1111/j.1532-5415.2005.00537.x · DOI
  9. Hobson, 2004, Risk and incidence of dementia in a cohort of older subjects with Parkinson’s disease in the United Kingdom, Mov Disord, 19, 1043, 10.1002/mds.20216 · DOI
  10. Ancelin, 2006, Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study, BMJ, 332, 445, 10.1136/bmj.38740.439664.DE · DOI · Paper page
  11. Hilmer, 2007, A drug burden index to define the functional burden of medications in older people, Arch Intern Med, 167, 781, 10.1001/archinte.167.8.781 · DOI
  12. Nebes, 2007, Serum anticholinergic activity and motor performance in elderly persons, J Gerontol A Biol Sci Med Sci, 62, 83, 10.1093/gerona/62.1.83 · DOI
  13. Kay, 2005, Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly, Clin Ther, 27, 127, 10.1016/j.clinthera.2005.01.006 · DOI
  14. Bymaster, 2003, Use of M1-M5 muscarinic receptor knockout mice as novel tools to delineate the physiological roles of the muscarinic cholinergic system, Neurochem Res, 28, 437, 10.1023/A:1022844517200 · DOI
  15. Gautam, 2006, M1-M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes, J Mol Neurosci, 30, 157, 10.1385/JMN:30:1:157 · DOI
  16. Anagnostaras, 2003, Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice, Nat Neurosci, 6, 51, 10.1038/nn992 · DOI
  17. Messer, 1990, Evidence for a preferential involvement of M1 muscarinic receptors in representational memory, Neurosci Lett, 116, 184, 10.1016/0304-3940(90)90407-Z · DOI
  18. Silman, 2004, Cholinergic Mechanisms: Function and Dysfunction, 10.3109/9780203493878 · DOI
  19. Fisher, 2000, Therapeutic strategies in Alzheimer’s disease: M1 muscarinic agonists, Jpn J Pharmacol, 84, 101, 10.1254/jjp.84.101 · DOI
  20. Yamada, 2001, Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean, Nature, 410, 207, 10.1038/35065604 · DOI
  21. Bowman, 2007, Blood-brain barrier impairment in Alzheimer disease: stability and functional significance, Neurology, 68, 1809, 10.1212/01.wnl.0000262031.18018.1a · DOI
  22. Pakulski, 2000, Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier, Med Sci Monit, 6, 314
  23. Yeung, 2008, Decreased junctional adhesion molecule - a expression during blood-brain barrier breakdown, Acta Neuropathol, 115, 635, 10.1007/s00401-008-0364-4 · DOI
  24. Maruyama, 2007, In vivo analysis of brain muscarinic receptor occupancy after oral oxybutynin in conscious rhesus monkey by using positron emission tomography (PET), Neurourol Urodynam, 26, 703
  25. Pahlman, 2001, Tissue distribution of tolterodine, a muscarinic receptor antagonist, and transfer into fetus and milk in mice, Arzneimittelforschung, 51, 125
  26. Devineni, 2005, Low central nervous system (CNS) penetration by darifenacin in rats, AAPS J, 7, T2277
  27. Skerjanec, 2004, Affinity of Darifenacin for the P-Glycoprotein Efflux Pump: a Mechanism Contributing to the CNS Sparing Profile?
  28. Geyer J Gavrilova O Brain penetration and organ distribution of trospium chloride and oxybutynin: the role of the multidrug resistance transporter MDR1 2008 · DOI
  29. Bierman, 2007, Sex differences in inappropriate prescribing among elderly veterans, Am J Geriatr Pharmacother, 5, 147, 10.1016/j.amjopharm.2007.06.005 · DOI
  30. Moriya, 1999, Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland, Life Sci, 64, 2351, 10.1016/S0024-3205(99)00188-5 · DOI
  31. Nelson, 2004, Functional selectivity of muscarinic receptor antagonists for inhibition of M3-mediated phosphoinositide responses in guinea pig urinary bladder and submandibular salivary gland, J Pharmacol Exp Ther, 310, 1255, 10.1124/jpet.104.067140 · DOI
  32. Ikeda, 2002, M3 receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland, Naunyn Schmiedebergs Arch Pharmacol, 366, 103, 10.1007/s00210-002-0554-x · DOI
  33. Ohtake, 2007, Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents, Biol Pharm Bull, 30, 54, 10.1248/bpb.30.54 · DOI
  34. Gillberg, 1998, Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists, Eur J Pharmacol, 349, 285, 10.1016/S0014-2999(98)00214-3 · DOI
  35. Oki, 2005, Muscarinic receptor binding, plasma concentration and inhibition of salivation after oral administration of a novel antimuscarinic agent, solifenacin succinate in mice, Br J Pharmacol, 145, 219, 10.1038/sj.bjp.0706184 · DOI
  36. Smith, 1997, Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors, J Recept Signal Transduct Res, 17, 177, 10.3109/10799899709036602 · DOI
  37. Watson, 1999, Comparative pharmacology of recombinant human M3 and M5 muscarinic receptors expressed in CHO-K1 cells, Br J Pharmacol, 127, 590, 10.1038/sj.bjp.0702551 · DOI
  38. Maruyama, 2006, Human muscarinic receptor binding characteristics of antimuscarinic agents to treat overactive bladder, J Urol, 175, 365, 10.1016/S0022-5347(05)00017-0 · DOI
  39. Oka, 2001, Effects of antimuscarinic drugs on both urinary frequency and cognitive impairment in conscious, nonrestrained rats, Jpn J Pharmacol, 87, 27, 10.1254/jjp.87.27 · DOI
  40. Sugiyama, 1999, Oxybutynin disrupts learning and memory in the rat passive avoidance response, Urol Res, 27, 393, 10.1007/s002400050169 · DOI
  41. Suzuki, 2007, Effect of antimuscarinic drugs used for overactive bladder on learning in a rat passive avoidance response test, Eur J Pharmacol, 557, 154, 10.1016/j.ejphar.2006.11.054 · DOI
  42. Cappon, 2008, Tolterodine does not affect memory assessed by passive-avoidance response test in mice, Eur J Pharmacol, 579, 225, 10.1016/j.ejphar.2007.10.063 · DOI
  43. Kay, 2005, Pharmacodynamic effects of darifenacin, a muscarinic M3 selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers, BJU Int, 96, 1055, 10.1111/j.1464-410X.2005.05745.x · DOI
  44. Lipton, 2005, Assessment of cognitive function of the elderly population: effects of darifenacin, J Urol, 173, 493, 10.1097/01.ju.0000148963.21096.5d · DOI
  45. Kay, 2006, Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects, Eur Urol, 50, 317, 10.1016/j.eururo.2006.03.057 · DOI
  46. Kay, 2006, Differential effects of the antimuscarinic agents tolterodine tartrate and oxybutynin ER on recent memory in older subjects, ICS
  47. Nagels, 2004, A prospective randomized double blind cross-over dose-titration study to evaluate the cognitive safety profile of tolterodine as compared to oxybutynin in multiple sclerosis patients with a neurogenic overactive bladder: a planned interim analysis, ICS
  48. Katz, 1998, Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride, J Am Geriatr Soc, 46, 8, 10.1111/j.1532-5415.1998.tb01006.x · DOI
  49. Diefenbach, 2003, Randomised double-blind study of the effects of oxybutynin tolterodine trospium chloride and placebo on sleep in healthy young volunteers, Clin Drug Invest, 23, 395, 10.2165/00044011-200323060-00003 · DOI
  50. Diefenbach, 2005, Effects on sleep of anticholinergics used for overactive bladder treatment in healthy volunteers aged ≥ 50 years, BJU Int, 95, 346, 10.1111/j.1464-410X.2005.05296.x · DOI
  51. Diefenbach, 2008, Effect of tolterodine on sleep structure modulated by CYP2D6 genotype, Sleep Med, 9, 579, 10.1016/j.sleep.2007.07.019 · DOI
  52. Pietzko, 1994, Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers, Eur J Clin Pharmacol, 47, 337, 10.1007/BF00191165 · DOI
  53. Todorova, 2001, Effects of tolterodine, trospium chloride and oxybutynin the central nervous system, J Clin Pharmacol, 41, 636, 10.1177/00912700122010528 · DOI
  54. Staskin, 2004, Effect of trospium chloride on somnolence and sleepiness in patients with overactive bladder, Curr Urol Rep, 5, 423, 10.1007/s11934-004-0064-0 · DOI

Cited by

Sorted by citations

Metadata

Authors
Kay, G. G., & Ebinger, U.
Affiliations
  • Cognitive Research (United States) (US)
  • Novartis (United States) (US)
Venue
International Journal of Clinical Practice
Publisher
Hindawi Limited
Published
2008-08-11
Volume
62
Issue
11
Pages
1792-1800
ISSN
1368-5031 (ISSN-L)
DOI
10.1111/j.1742-1241.2008.01849.x
PMC
PMC2734922
OpenAlex
W1578634963
Cited by
141
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 12 · 2015: 6 · 2014: 8 · 2013: 10 · 2012: 16
FWCI
2.52
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Clinical Practice (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • Novartis Pharmaceuticals Corporation
  • Astellas Pharma
  • Novartis Pharma
Topics
  • Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Health Sciences › Medicine › Urology › Urinary Tract Infections Management
Keywords
overactive bladder, cognitive impairment, darifenacin, oxybutynin, antimuscarinic agents, central nervous system adverse effects, memory, tolterodine, solifenacin, trospium, elderly patients, neurogenic bladder, multiple sclerosis, Parkinson's disease
MeSH terms
Adult, Aged, Animals, Benzofurans, Central Nervous System, Cognition Disorders, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Pyrrolidines, Randomized Controlled Trials as Topic, Muscarinic Antagonists, Rats, Urinary Bladder, Overactive

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review