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Considerations in the Medically Complex and Frail Elderly

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Abstract

Overactive bladder (OAB) and urgency urinary incontinence (UUI) in the medically complex and frail elderly are highly prevalent and are associated with significant adverse consequences in terms of quality of life and health outcomes. OAB management in this group of patients requires the treating clinician to take a broader view of the condition and its effect on the patient. The underlying physiological change in the lower urinary tract, coupled with age- and pathology-associated central nervous system changes, mean that OAB in older people appears to be more than just bladder dysfunction. Until relatively recently there was a paucity of evidence available which specifically addressed treatment in the medically complex or frail older person. Evidence is still largely restricted to cognitively intact elderly, and relevant studies on cognitively impaired persons are still lacking. This chapter discusses what evidence exists for drug treatment of OAB-UUI in the medically complex and frail and the additional factors which might need to be taken into account in order to achieve the best outcomes from treatment.

Keyword

Medically complex Multimorbidity Elderly Frailty Overactive bladder urgency incontinence 

References

  1. 1.
    Meng X, D’Arcy C. Successful aging in Canada: prevalence and predictors from a population-based sample of older adults. Gerontology. 2014;60(1):65–72.PubMedCrossRefGoogle Scholar
  2. 2.
    Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50(6):1306–14; discussion 14-5.PubMedCrossRefGoogle Scholar
  3. 3.
    Wagg A, Gibson W, Ostaszkiewicz J, Johnson T 3rd, Markland A, Palmer MH, et al. Urinary incontinence in frail elderly persons: report from the 5th International Consultation on Incontinence. Neurourol Urodyn. 2015;34(5):398–406.PubMedCrossRefGoogle Scholar
  4. 4.
    Griffiths D, Tadic SD, Schaefer W, Resnick NM. Cerebral control of the bladder in normal and urge-incontinent women. NeuroImage. 2007;37(1):1–7.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Ylikoski A, Erkinjuntti T, Raininko R, Sarna S, Sulkava R, Tilvis R. White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. Stroke. 1995;26(7):1171–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Wakefield DB, Moscufo N, Guttmann CR, Kuchel GA, Kaplan RF, Pearlson G, et al. White matter hyperintensities predict functional decline in voiding, mobility, and cognition in older adults. J Am Geriatr Soc. 2010;58(2):275–81.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Enzinger C, Linortner P, Schmidt R, Ropele S, Pendl B, Petrovic K, et al. White matter hyperintensities alter the functional organization of the motor system with ageing—first evidence from FMRI (Oral Communication). 19th European Stroke Conference; 2010 May 26–29; Barcelona, Spain. Cerebrovascular Diseases 2010; 29(Suppl):79.Google Scholar
  8. 8.
    Prins ND, Scheltens P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol. 2015;11(3):157–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Sakakibara R, Panicker J, Fowler CJ, Tateno F, Kishi M, Tsuyuzaki Y, et al. Vascular incontinence: incontinence in the elderly due to ischemic white matter changes. Neurol Int. 2012;4(2):e13.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Tadic SD, Griffiths D, Murrin A, Schaefer W, Aizenstein HJ, Resnick NM. Brain activity during bladder filling is related to white matter structural changes in older women with urinary incontinence. NeuroImage. 2010;51(4):1294–302.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Ganz ML, Liu J, Zou KH, Bhagnani T, Luo X. Real-world characteristics of elderly patients with overactive bladder in the United States. Curr Med Res Opin. 2016;32(12):1997–2005.PubMedCrossRefGoogle Scholar
  12. 12.
    Zarowitz BJ, Allen C, O’Shea T, Tangalos E, Berner T, Ouslander JG. Clinical burden and nonpharmacologic management of nursing facility residents with overactive bladder and/or urinary incontinence. Consult Pharm. 2015;30(9):533–42.PubMedCrossRefGoogle Scholar
  13. 13.
    Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489–95.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Wang CJ, Hung CH, Tang TC, Chen LY, Peng LN, Hsiao FY, et al. Urinary incontinence and its association with frailty among men aged 80 years and older in Taiwan: a cross-sectional study. Rejuvenation Res. 2017;20(2):111–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Miles TP, Palmer RF, Espino DV, Mouton CP, Lichtenstein MJ, Markides KS. New-onset incontinence and markers of frailty: data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly. J Gerontol A Biol Sci Med Sci. 2001;56(1):M19–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Silva VA, Souza KL, D’Elboux MJ. Urinary incontinence and the criteria of frailness among the elderly outpatients. Rev Esc Enferm USP. 2011;45(3):672–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Rochon PA, Anderson GM, Tu JV, Gurwitz JH, Clark JP, Shear NH, et al. Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose. J Am Geriatr Soc. 1999;47(8):954–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Bemelmans BL, Kiemeney LA, Debruyne FM. Low-dose oxybutynin for the treatment of urge incontinence: good efficacy and few side effects. Eur Urol. 2000;37(6):709–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Malone-Lee J, Lubel D, Szonyi G. Low dose oxybutynin for the unstable bladder. BMJ. 1992;304(6833):1053.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV. Comparative effectiveness of combined low- and standard-dose trospium and solifenacin for moderate overactive bladder symptoms in elderly men and women. Urol Int. 2014;93(4):470–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Wagg A, Wyndaele JJ, Sieber P. Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. Am J Geriatr Pharmacother. 2006;4(1):14–24.PubMedCrossRefGoogle Scholar
  22. 22.
    Kraus SR, Ruiz-Cerda JL, Martire D, Wang JT, Wagg AS. Efficacy and tolerability of fesoterodine in older and younger subjects with overactive bladder. Urology. 2010;76(6):1350–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Dubeau CE, Kraus SR, Griebling TL, Newman DK, Wyman JF, Johnson TM 2nd, et al. Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: a double-blind, placebo-controlled trial. J Urol. 2014;191(2):395–404.PubMedCrossRefGoogle Scholar
  24. 24.
    Wagg A, Khullar V, Marschall-Kehrel D, Michel MC, Oelke M, Darekar A, et al. Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial. J Am Geriatr Soc. 2013;61(2):185–93.CrossRefGoogle Scholar
  25. 25.
    Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC. Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011. JAMA Intern Med. 2016;176(4):473–82.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Kashyap M, Tu le M, Tannenbaum C. Prevalence of commonly prescribed medications potentially contributing to urinary symptoms in a cohort of older patients seeking care for incontinence. BMC Geriatr. 2013;13:57.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Cresswell KM, Fernando B, McKinstry B, Sheikh A. Adverse drug events in the elderly. Br Med Bull. 2007;83:259–74.PubMedCrossRefGoogle Scholar
  28. 28.
    Hofer-Dueckelmann C, Prinz E, Beindl W, Szymanski J, Fellhofer G, Pichler M, et al. Adverse drug reactions (ADRs) associated with hospital admissions—elderly female patients are at highest risk. Int J Clin Pharmacol Ther. 2011;49(10):577–86.PubMedCrossRefGoogle Scholar
  29. 29.
    Rodenburg EM, Stricker BH, Visser LE. Sex differences in cardiovascular drug-induced adverse reactions causing hospital admissions. Br J Clin Pharmacol. 2012 Dec;74(6):1045–52.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging. 1993;3(4):335–48.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Hopcraft MS, Tan C. Xerostomia: an update for clinicians. Aust Dent J. 2010;55(3):238–44; quiz 353.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Herschorn S, Pommerville P, Stothers L, Egerdie B, Gajewski J, Carlson K, et al. Tolerability of solifenacin and oxybutynin immediate release in older (> 65 years) and younger (</= 65 years) patients with overactive bladder: sub-analysis from a Canadian, randomized, double-blind study. Curr Med Res Opin. 2011;27(2):375–82.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Chapple CR, Nilvebrant L. Tolterodine: selectivity for the urinary bladder over the eye (as measured by visual accommodation) in healthy volunteers. Drugs R D. 2002;3(2):75–81.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Altan-Yaycioglu R, Yaycioglu O, Aydin Akova Y, Guvel S, Ozkardes H. Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective randomized trial. Br J Clin Pharmacol. 2005;59(5):588–92.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Wagg A, Arumi D, Herschorn S, Angulo Cuesta J, Haab F, Ntanios F, et al. A pooled analysis of the efficacy of fesoterodine for the treatment of overactive bladder, and the relationship between safety, co-morbidity and polypharmacy in patients aged 65 years or older. Age Ageing. 2017;46(4):620–6.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Fox C, Richardson K, Maidment ID, Savva GM, Matthews FE, Smithard D, et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc. 2011;59(8):1477–83.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401–7.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Carriere I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317–24.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Richardson K, Fox C, Maidment I, Steel N, Loke YK, Arthur A, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Salahudeen MS, Chyou TY, Nishtala PS. Serum anticholinergic activity and cognitive and functional adverse outcomes in older people: a systematic review and meta-analysis of the literature. PLoS One. 2016;11(3):e0151084.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Sumukadas D, McMurdo ME, Mangoni AA, Guthrie B. Temporal trends in anticholinergic medication prescription in older people: repeated cross-sectional analysis of population prescribing data. Age Ageing. 2014;43(4):515–21.PubMedCrossRefGoogle Scholar
  42. 42.
    Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401–7.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kay GG, Abou-Donia MB, Messer WS Jr, Murphy DG, Tsao JW, Ouslander JG. Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc. 2005;53(12):2195–201.PubMedCrossRefGoogle Scholar
  44. 44.
    Wagg A. The cognitive burden of anticholinergics in the elderly—implications for the treatment of overactive bladder. Eur Urol Rev. 2012;7(1):42–9.Google Scholar
  45. 45.
    Fox C, Livingston G, Maidment ID, Coulton S, Smithard DG, Boustani M, et al. The impact of anticholinergic burden in Alzheimer’s dementia-the LASER-AD study. Age Ageing. 2011;40(6):730–5.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Whalley LJ, Sharma S, Fox HC, Murray AD, Staff RT, Duthie AC, et al. Anticholinergic drugs in late life: adverse effects on cognition but not on progress to dementia. J Alzheimers Dis. 2012;30(2):253–61.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Ouslander JG, Uman GC, Urman HN, Rubenstein LZ. Incontinence among nursing home patients: clinical and functional correlates. J Am Geriatr Soc. 1987;35(4):324–30.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Østbye T, Borrie MJ, Hunskaar S. The prevalence of urinary incontinence in elderly Canadians and its association with dementia, ambulatory function, and institutionalization. Norsk Epidemiologi. 2009;8(2):177–82.CrossRefGoogle Scholar
  49. 49.
    Huang AJ, Brown JS, Thom DH, Fink HA, Yaffe K, Study of Osteoporotic Fractures Research G. Urinary incontinence in older community-dwelling women: the role of cognitive and physical function decline. Obstet Gynecol. 2007;109(4):909–16.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Ostbye T, Seim A, Krause KM, Feightner J, Hachinski V, Sykes E, et al. A 10-year follow-up of urinary and fecal incontinence among the oldest old in the community: the Canadian Study of Health and Aging. Can J Aging. 2004;23(4):319–31.PubMedCrossRefGoogle Scholar
  51. 51.
    Byles J, Millar CJ, Sibbritt DW, Chiarelli P. Living with urinary incontinence: a longitudinal study of older women. Age Ageing. 2009;38(3):333–8. discussion 251PubMedCrossRefGoogle Scholar
  52. 52.
    Thom DH, Haan MN, Van Den Eeden SK. Medically recognized urinary incontinence and risks of hospitalization, nursing home admission and mortality. Age Ageing. 1997;26(5):367–74.PubMedCrossRefGoogle Scholar
  53. 53.
    Alcorn G, Law E, Connelly PJ, Starr JM. Urinary incontinence in people with Alzheimer’s disease. Int J Geriatr Psychiatry. 2014;29(1):107–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Grant RL, Drennan VM, Rait G, Petersen I, Iliffe S. First diagnosis and management of incontinence in older people with and without dementia in primary care: a cohort study using The Health Improvement Network primary care database. PLoS Med. 2013;10(8):e1001505.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Resnick NM, Yalla SV, Laurino E. The pathophysiology of urinary incontinence among institutionalized elderly persons. N Engl J Med. 1989;320(1):1–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Lee SH, Cho ST, Na HR, Ko SB, Park MH. Urinary incontinence in patients with Alzheimer’s disease: relationship between symptom status and urodynamic diagnoses. Int J Urol. 2014;21(7):683–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Cassells C, Watt E. The impact of incontinence on older spousal caregivers. J Adv Nurs. 2003;42(6):607–16.PubMedCrossRefGoogle Scholar
  58. 58.
    Starr JM. Cholinesterase inhibitor treatment and urinary incontinence in Alzheimer’s disease. J Am Geriatr Soc. 2007;55(5):800–1.PubMedCrossRefGoogle Scholar
  59. 59.
    Kroger E, Van Marum R, Souverein P, Carmichael PH, Egberts T. Treatment with rivastigmine or galantamine and risk of urinary incontinence: results from a Dutch database study. Pharmacoepidemiol Drug Saf. 2015;24(3):276–85.PubMedCrossRefGoogle Scholar
  60. 60.
    Siegler EL, Reidenberg M. Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia. Clin Pharmacol Ther. 2004;75(5):484–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Gill S, Mamdani M, Naglie G, Streiner DL, Bronskill SE, Kopp A, Shulman KI, Lee PE, Rochon PA. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med. 2005;165(7):808–13.PubMedCrossRefGoogle Scholar
  62. 62.
    Zarowitz BJ, Allen C, O’Shea T, Tangalos EG, Berner T, Ouslander JG. Challenges in the pharmacological management of nursing home residents with overactive bladder or urinary incontinence. J Am Geriatr Soc. 2015;63(11):2298–307.PubMedCrossRefGoogle Scholar
  63. 63.
    Isik AT, Celik T, Bozoglu E, Doruk H. Trospium and cognition in patients with late onset Alzheimer disease. J Nutr Health Aging. 2009;13(8):672–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Sink KM, Thomas J 3rd, Xu H, Craig B, Kritchevsky S, Sands LP. Dual use of bladder anticholinergics and cholinesterase inhibitors: long-term functional and cognitive outcomes. J Am Geriatr Soc. 2008;56(5):847–53.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Sakakibara R, Ogata T, Uchiyama T, Kishi M, Ogawa E, Isaka S, et al. How to manage overactive bladder in elderly individuals with dementia? A combined use of donepezil, a central acetylcholinesterase inhibitor, and propiverine, a peripheral muscarine receptor antagonist. J Am Geriatr Soc. 2009;57(8):1515–7.PubMedCrossRefGoogle Scholar
  66. 66.
    WebMD L. Rx List: the internet drug index: Web MD; 2012. Available from: http://www.rxlist.com/toviaz-drug.htm. Accessed 28 May 2018.
  67. 67.
    Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR. The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers. Med Chem. 2007;3(6):543–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Napier C, Gupta P. Darifenacin is selective for the human recombinant M3 receptor subtype (abstract). Neurourol Urodyn. 2002;21:A445.Google Scholar
  69. 69.
    Ikeda K, Kobayashi S, Suzuki M, Miyata K, Takeuchi M, Yamada T, et al. M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. Naunyn Schmiedeberg’s Arch Pharmacol. 2002;366(2):97–103.CrossRefGoogle Scholar
  70. 70.
    Kobayashi S1, Ikeda K, Miyata K. Comparison of in vitro selectivity profiles of solifenacin succinate (YM905) and current antimuscarinic drugs in bladder and salivary glands: a Ca2+ mobilization study in monkey cells. Life Sci. 2004;74(7):843–53.PubMedCrossRefGoogle Scholar
  71. 71.
    Wagg A, Verdejo C, Molander U. Review of cognitive impairment with antimuscarinic agents in elderly patients with overactive bladder. Int J Clin Pract. 2010;64(9):1279–86.PubMedCrossRefGoogle Scholar
  72. 72.
    Wuest M, Weiss A, Waelbroeck M, Braeter M, Kelly LU, Hakenberg OW, et al. Propiverine and metabolites: differences in binding to muscarinic receptors and in functional models of detrusor contraction. Naunyn Schmiedeberg’s Arch Pharmacol. 2006;374(2):87–97.CrossRefGoogle Scholar
  73. 73.
    Kobayashi F, Yageta Y, Yamazaki T, Wakabayashi E, Inoue M, Segawa M, et al. Pharmacological effects of imidafenacin (KRP-197/ONO-8025), a new bladder selective anti-cholinergic agent, in rats. Comparison of effects on urinary bladder capacity and contraction, salivary secretion and performance in the Morris water maze task. Arzneimittelforschung. 2007;57(3):147–54.Google Scholar
  74. 74.
    Paquette A, Gou P, Tannenbaum C. Systematic review and meta-analysis: do clinical trials testing antimuscarinic agents for overactive bladder adequately measure central nervous system adverse events? J Am Geriatr Soc. 2011;59(7):1332–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Kistler KD, Xu Y, Zou KH, Ntanios F, Chapman DS, Luo X. Systematic literature review of clinical trials evaluating pharmacotherapy for overactive bladder in elderly patients: an assessment of trial quality. Neurourol Urodyn. 2018;37(1):54–66.PubMedCrossRefGoogle Scholar
  76. 76.
    Chapple C, DuBeau C, Ebinger U, Rekeda L, Viegas A. Darifenacin treatment of patients >or= 65 years with overactive bladder: results of a randomized, controlled, 12-week trial. Curr Med Res Opin. 2007;23(10):2347–58.PubMedCrossRefGoogle Scholar
  77. 77.
    Hill S, Elhilali M, Millard RJ, Dwyer PL, Lheritier K, Kawakami FT, et al. Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study. Curr Med Res Opin. 2007;23(11):2697–704.PubMedCrossRefGoogle Scholar
  78. 78.
    Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol. 2005;173(2):493–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Kay G, Crook T, Rekeda L, Lima R, Ebinger U, Arguinzoniz M, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50(2):317–26.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Malhotra BK, Wood N, Sachse R. Influence of age, gender, and race on pharmacokinetics, pharmacodynamics, and safety of fesoterodine. Int J Clin Pharmacol Ther. 2009;47(9):570–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Sand PK, Heesakkers J, Kraus SR, Carlsson M, Guan Z, Berriman S. Long-term safety, tolerability and efficacy of fesoterodine in subjects with overactive bladder symptoms stratified by age: pooled analysis of two open-label extension studies. Drugs Aging. 2012;29(2):119–31.CrossRefGoogle Scholar
  82. 82.
    Wagg A, Khullar V, Michel MC, Oelke M, Darekar A, Bitoun CE. Long-term safety, tolerability and efficacy of flexible-dose fesoterodine in elderly patients with overactive bladder: open-label extension of the SOFIA trial. Neurourol Urodyn. 2014;33(1):106–14.PubMedCrossRefGoogle Scholar
  83. 83.
    Wagg A, Darekar A, Arumi D, Khullar V, Oelke M. Factors associated with dose escalation of fesoterodine for treatment of overactive bladder in people >65 years of age: a post hoc analysis of data from the SOFIA study. Neurourol Urodyn. 2015;34(5):438–43.PubMedCrossRefGoogle Scholar
  84. 84.
    Min L, Yoon W, Mariano J, Wenger NS, Elliott MN, Kamberg C, et al. The vulnerable elders-13 survey predicts 5-year functional decline and mortality outcomes in older ambulatory care patients. J Am Geriatr Soc. 2009;57(11):2070–6.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Dubeau CE, Kraus SR, Griebling TL, Newman DK, Wyman JF, Johnson TM 2nd, et al. Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: a double-blind, placebo controlled trial. J Urol. 2014;191(2):395–404.PubMedCrossRefGoogle Scholar
  86. 86.
    Dell’Atti L. Efficacy of Tadalafil once daily versus Fesoterodine in the treatment of overactive bladder in older patients. Eur Rev Med Pharmacol Sci. 2015;19(9):1559–63.PubMedGoogle Scholar
  87. 87.
    Kay GG, Maruff P, Scholfield D, Malhotra B, Whelan L, Darekar A, et al. Evaluation of cognitive function in healthy older subjects treated with fesoterodine. Postgrad Med. 2012;124(3):7–15.PubMedCrossRefGoogle Scholar
  88. 88.
    Ohno T, Nakayama K, Nakade S, Kitagawa J, Ueda S, Miyabe H, et al. Effect of itraconazole on the pharmacokinetics of imidafenacin in healthy subjects. J Clin Pharmacol. 2008;48(3):330–4.PubMedCrossRefGoogle Scholar
  89. 89.
    Ohno T, Nakade S, Nakayama K, Kitagawa J, Ueda S, Miyabe H, et al. Absolute bioavailability of imidafenacin after oral administration to healthy subjects. Br J Clin Pharmacol. 2008;65(2):197–202.PubMedCrossRefGoogle Scholar
  90. 90.
    Shiota T, Torimoto K, Momose H, Nakamuro T, Mochizuki H, Kumamoto H, et al. Temporary cognitive impairment related to administration of newly developed anticholinergic medicines for overactive bladder: two case reports. BMC Res Notes. 2014;7:672.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Sakakibara R, Tateno F, Yano M, Takahashi O, Sugiyama M, Ogata T, et al. Imidafenacin on bladder and cognitive function in neurologic OAB patients. Clin Auton Res. 2013;23(4):189–95.PubMedCrossRefGoogle Scholar
  92. 92.
    Michel MC, Korstanje C. beta3-Adrenoceptor agonists for overactive bladder syndrome: role of translational pharmacology in a repositioning clinical drug development project. Pharmacol Ther. 2016;159:66–82.PubMedCrossRefGoogle Scholar
  93. 93.
    Wagg A, Cardozo L, Nitti VW, Castro-Diaz D, Auerbach S, Blauwet MB, et al. The efficacy and tolerability of the beta3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients. Age Ageing. 2014;43(5):666–75.PubMedCrossRefGoogle Scholar
  94. 94.
    Kosilov K, Loparev S, Ivanovskaya M, Kosilova L. A randomized, controlled trial of effectiveness and safety of management of OAB symptoms in elderly men and women with standard-dosed combination of solifenacin and mirabegron. Arch Gerontol Geriatr. 2015;61(2):212–6.CrossRefGoogle Scholar
  95. 95.
    Matsukawa Y, Takai S, Funahashi Y, Yamamoto T, Gotoh M. Urodynamic evaluation of the efficacy of mirabegron on storage and voiding functions in women with overactive bladder. Urology. 2015;85(4):786–90.PubMedCrossRefGoogle Scholar
  96. 96.
    Herschorn S, Chapple CR, Abrams P, Arlandis S, Mitcheson D, Lee KS, et al. Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study). BJU Int. 2017;120(4):562–75.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Gibson W, MacDiarmid S, Huang M, Siddiqui E, Stolzel M, Choudhury N, et al. Treating overactive bladder in older patients with a combination of Mirabegron and Solifenacin: a Prespecified analysis from the BESIDE study. Eur Urol Focus. 2017;3(6):629–38.PubMedCrossRefGoogle Scholar
  98. 98.
    Bundgaard H, Axelsson A, Hartvig Thomsen J, Sorgaard M, Kofoed KF, Hasselbalch R, et al. The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial. Eur J Heart Fail. 2017;19(4):566–75.PubMedCrossRefGoogle Scholar
  99. 99.
    Lee CL, Kuo HC. Efficacy and safety of mirabegron, a beta3 -adrenoceptor agonist, in patients with detrusor hyperactivity and impaired contractility. Low Urin Tract Symptoms. 2018. Apr 26. https://doi.org/10.1111/luts.12224.
  100. 100.
    Szonyi G, Collas DM, Ding YY, Malone-Lee JG. Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial. Age Ageing. 1995;24(4):287–91.PubMedCrossRefGoogle Scholar
  101. 101.
    Lackner TE, Wyman JF, McCarthy TC, Monigold M, Davey C. Randomized, placebo-controlled trial of the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired nursing home residents with urge urinary incontinence. J Am Geriatr Soc. 2008;56(5):862–70.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Lackner TE, Wyman JF, McCarthy TC, Monigold M, Davey C. Efficacy of oral extended-release oxybutynin in cognitively impaired older nursing home residents with urge urinary incontinence: a randomized placebo-controlled trial. J Am Med Dir Assoc. 2011;12(9):639–47.PubMedCrossRefGoogle Scholar
  103. 103.
    Minassian VA, Ross S, Sumabat O, Lovatsis D, Pascali D, Al-Badr A, et al. Randomized trial of oxybutynin extended versus immediate release for women aged 65 and older with overactive bladder: lessons learned from conducting a trial. J Obstet Gynaecol Can. 2007;29(9):726–32.PubMedCrossRefGoogle Scholar
  104. 104.
    Sand P, Zinner N, Newman D, Lucente V, Dmochowski R, Kelleher C, et al. Oxybutynin transdermal system improves the quality of life in adults with overactive bladder: a multicentre, community-based, randomized study. BJU Int. 2007;99(4):836–44.PubMedCrossRefGoogle Scholar
  105. 105.
    Ouslander JG, Blaustein J, Connor A, Pitt A. Habit training and oxybutynin for incontinence in nursing home patients: a placebo-controlled trial. J Am Geriatr Soc. 1988;36(1):40–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Ouslander JG, Schnelle JF, Uman G, Fingold S, Nigam JG, Tuico E, et al. Does oxybutynin add to the effectiveness of prompted voiding for urinary incontinence among nursing home residents? A placebo-controlled trial. J Am Geriatr Soc. 1995;43(6):610–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Zorzitto ML, Holliday PJ, Jewett MA, Herschorn S, Fernie GR. Oxybutynin chloride for geriatric urinary dysfunction: a double-blind placebo-controlled study. Age Ageing. 1989;18(3):195–200.PubMedCrossRefGoogle Scholar
  108. 108.
    Kay GG, Staskin DR, Macdiarmid S, McIlwain M, Dahl NV. Cognitive effects of oxybutynin chloride topical gel in older healthy subjects: a 1-week, randomized, double-blind, placebo- and active-controlled study. Clin Drug Investig. 2012;32(10):707–14.PubMedCrossRefGoogle Scholar
  109. 109.
    Staskin DR, Dmochowski RR, Sand PK, Macdiarmid SA, Caramelli KE, Thomas H, et al. Efficacy and safety of oxybutynin chloride topical gel for overactive bladder: a randomized, double-blind, placebo controlled, multicenter study. J Urol. 2009;181(4):1764–72.PubMedCrossRefGoogle Scholar
  110. 110.
    Gibson W, Athanasopoulos A, Goldman H, Madersbacher H, Newman D, Spinks J, et al. Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence? Int J Clin Pract. 2014;68(9):1165–73.PubMedCrossRefGoogle Scholar
  111. 111.
    Biardeau X, Campeau L, Corcos J. We should not use oxybutynin chloride in OAB. Neurourol Urodyn. 2017;36(3):822–3.PubMedCrossRefGoogle Scholar
  112. 112.
    National Collaborating Centre for Women’s and Children’s Health (UK). Urinary incontinence in women: the management of urinary incontinence in women. London: Royal College of Obstetricians and Gynaecologists (UK); 2013. National Institute for Health and Care Excellence: Clinical Guidelines.Google Scholar
  113. 113.
    Lucas MG, Bedretdinova D, Berghmans LC, Bosch JLHR, Burkhard FC, Cruz AK, et al. Guidelines on urinary incontinence. European Association of Urology Web site. http://uroweb.org/wp-content/uploads/20-Urinary-Incontinence_LR1.pdf. Updated 2015. Accessed 28 May 2018.
  114. 114.
    Madersbacher H, Murtz G. Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic). World J Urol. 2001;19(5):324–35.PubMedCrossRefGoogle Scholar
  115. 115.
    Mori S, Kojima M, Sakai Y, Nakajima K. Bladder dysfunction in dementia patients showing urinary incontinence: evaluation with cystometry and treatment with propiverine hydrochloride. Nippon Ronen Igakkai Zasshi. 1999;36(7):489–94 [Article in Japanese].PubMedCrossRefGoogle Scholar
  116. 116.
    Otomo E, Maruyama S, Kobayashi I, et al. Clinical evaluation of propiverine hydrochloride (P-4) on urinary disturbances due to neurological diseases. Jpn J Pharmacol. 1990;18:1731.Google Scholar
  117. 117.
    Dorschner W, Stolzenburg JU, Griebenow R, Halaska M, Brunjes R, Frank M, et al. The elderly patient with urge incontinence or urge-stress incontinence—efficacy and cardiac safety of propiverine. Aktuelle Urol. 2003;34(2):102–8.CrossRefGoogle Scholar
  118. 118.
    Oelke M, Becher K, Castro-Diaz D, Chartier-Kastler E, Kirby M, Wagg A, et al. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014). Age Ageing. 2015;44(5):745–55.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Oelke M, Murgas S, Schneider T, Heßdörfer E. Influence of propiverine er 30 mg once daily on cognitive function in elderly female and male patients with overactive bladder: a noninterventional study to assess real life data (abstract). Proceedings of the International Continence Society Annual Scientific Meeting Barcelona; 2013. 2013:201.Google Scholar
  120. 120.
    Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV. Effectiveness of solifenacin and trospium for managing of severe symptoms of overactive bladder in patients with benign prostatic hyperplasia. Am J Mens Health. 2016;10(2):157–63.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Michel MC, Wetterauer U, Vogel M, de la Rosette JJ. Cardiovascular safety and overall tolerability of solifenacin in routine clinical use: a 12-week, open-label, post-marketing surveillance study. Drug Saf. 2008;31(6):505–14.PubMedCrossRefGoogle Scholar
  122. 122.
    Wesnes KA, Edgar C, Tretter RN, Bolodeoku J. Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg. Expert Opin Drug Saf. 2009;8(6):615–26.PubMedCrossRefGoogle Scholar
  123. 123.
    Wagg A, Dale M, Tretter R, Stow B, Compion G. Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: the SENIOR study. Eur Urol. 2013;64(1):74–81.PubMedCrossRefGoogle Scholar
  124. 124.
    Zinner NR, Mattiasson A, Stanton SL. Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients. J Am Geriatr Soc. 2002;50(5):799–807.PubMedCrossRefGoogle Scholar
  125. 125.
    Millard R, Tuttle J, Moore K, Susset J, Clarke B, Dwyer P, et al. Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity. J Urol 1999;161(5):1551–5.PubMedCrossRefGoogle Scholar
  126. 126.
    Drutz HP, Appell RA, Gleason D, Klimberg I, Radomski S. Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct. 1999;10(5):283–9.CrossRefGoogle Scholar
  127. 127.
    Michel MC, Schneider T, Krege S, Goepel M. Does gender or age affect the efficacy and safety of tolterodine? J Urol. 2002;168(3):1027–31.PubMedCrossRefGoogle Scholar
  128. 128.
    Ouslander JG, Maloney C, Grasela TH, Rogers L, Walawander CA. Implementation of a nursing home urinary incontinence management program with and without tolterodine. J Am Med Dir Assoc. 2001;2(5):207–14.PubMedCrossRefGoogle Scholar
  129. 129.
    Tsao JW, Heilman KM. Transient memory impairment and hallucinations associated with tolterodine use. N Engl J Med. 2003;349(23):2274–5.PubMedCrossRefGoogle Scholar
  130. 130.
    Womack KB, Heilman KM. Tolterodine and memory: dry but forgetful. Arch Neurol. 2003;60(5):771–3.PubMedCrossRefGoogle Scholar
  131. 131.
    Salvatore S, Serati M, Cardozo L, Uccella S, Bolis P. Cognitive dysfunction with tolterodine use. Am J Obstet Gynecol. 2007;197(2):e8.PubMedCrossRefGoogle Scholar
  132. 132.
    Edwards KR, O’Connor JT. Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors. J Am Geriatr Soc. 2002;50(6):1165–6.PubMedCrossRefGoogle Scholar
  133. 133.
    Sand PK, Johnson Ii TM, Rovner ES, Ellsworth PI, Oefelein MG, Staskin DR. Trospium chloride once-daily extended release is efficacious and tolerated in elderly subjects (aged >/= 75 years) with overactive bladder syndrome. BJU Int. 2011;107(4):612–20.PubMedCrossRefGoogle Scholar
  134. 134.
    Sand PK, Rovner ES, Watanabe JH, Oefelein MG. Once-daily trospium chloride 60 mg extended release in subjects with overactive bladder syndrome who use multiple concomitant medications: post hoc analysis of pooled data from two randomized, placebo-controlled trials. Drugs Aging. 2011;28(2):151–60.PubMedCrossRefGoogle Scholar
  135. 135.
    Staskin D, Kay G, Tannenbaum C, Goldman HB, Bhashi K, Ling J, Oefelein MG. Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with overactive bladder. Int J Clin Pract. 2010;64(9):1294–300.PubMedCrossRefGoogle Scholar
  136. 136.
    Staskin D, Kay G, Tannenbaum C, Goldman HB, Bhashi K, Ling J, Oefelein MG. Trospium chloride is undetectable in older human central nervous system. J Am Geriatr Soc. 2010;58(8):1618–9.PubMedCrossRefGoogle Scholar
  137. 137.
    Panel. AGSBCUE. American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medicine, University of AlbertaEdmontonCanada

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