Anticholinergics for Overactive Bladder Therapy: Central Nervous System Effects

CNS Neuroscience and Therapeutics

Volumn 18, Issue 2, 2012, Pages 167-174

  Chancellor, Michael ^a   Boone, Timothy ^b  

^a OAKLAND UNIVERSITY WILLIAM BEAUMONT SCHOOL OF MEDICINE   (United States)

^b HOUSTON METHODIST HOSPITAL   (United States)

Author keywords

Antimuscarinic drugs; Blood brain barrier; CNS effects; Overactive bladder

Indexed keywords

CHOLINERGIC RECEPTOR BLOCKING AGENT; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DARIFENACIN; FESOTERODINE; MUSCARINIC M1 RECEPTOR; MUSCARINIC M2 RECEPTOR; MUSCARINIC M3 RECEPTOR; MUSCARINIC RECEPTOR BLOCKING AGENT; OXYBUTYNIN; PLACEBO; SOLIFENACIN; TOLTERODINE; TROSPIUM CHLORIDE;

ANXIETY; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; COGNITION; COGNITIVE DEFECT; CONSTIPATION; DIZZINESS; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG MONITORING; DRUG PENETRATION; DRUG SAFETY; ELECTROENCEPHALOGRAPHY; HUMAN; HYDROPHILICITY; LEARNING; LIPOPHILICITY; MEMORY; NERVOUSNESS; NEUROPROTECTION; OVERACTIVE BLADDER; RECEPTOR AFFINITY; REM SLEEP; REVIEW; SIDE EFFECT; SLEEP DISORDER; SLEEP QUALITY; SOMNOLENCE; UNSPECIFIED SIDE EFFECT; XEROSTOMIA;

BLOOD-BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; CHOLINERGIC ANTAGONISTS; COGNITION DISORDERS; HUMANS; SLEEP DISORDERS; URINARY BLADDER, OVERACTIVE;

EID: 84856793809     PISSN: 17555930     EISSN: 17555949     Source Type: Journal    
DOI: 10.1111/j.1755-5949.2011.00248.x     Document Type: Review

References (86)

1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: Report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002;21:167-178.
2. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327-336.
3. Coyne KS, Payne C, Bhattacharyya SK, et al. The impact of urinary urgency and frequency on health-related quality of life in overactive bladder: Results from a national community survey. Value Health 2004;7:455-463.
4. Hu TW, Wagner TH, Bentkover JD, et al. Estimated economic costs of overactive bladder in the United States. Urology 2003;61:1123-1128.
5. Chu FM, Dmochowski R. Pathophysiology of overactive bladder. Am J Med 2006;119:3-8.
6. Abrams P, Andersson KE. Muscarinic receptor antagonists for overactive bladder. BJU Int 2007;100:987-1006.
7. Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of antimuscarinic treatments in overactive bladder: A systematic review and meta-analysis. Eur Urol 2005;48:5-26.
8. Nabi G, Cody JD, Ellis G, Herbison P, Hay-Smith J. Anticholinergic drugs versus placebo for overactive bladder syndrome in adults. Cochrane Database Syst Rev 2006;CD003781, doi:.
9. Herbison P, Hay-Smith J, Ellis G, Moore K. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: Systematic review. BMJ 2003;326:841-844.
10. Alhasso AA, McKinlay J, Patrick K, Stewart L. Anticholinergic drugs versus non-drug active therapies for overactive bladder syndrome in adults. Cochrane Database Syst Rev 2006:CD003193, doi:.
11. Burgio KL, Kraus SR, Menefee S, et al. Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: A randomized trial. Ann Intern Med 2008;149:161-169.
12. Sussman DO. Overactive bladder: Treatment options in primary care medicine. J Am Osteopath Assoc 2007;107:379-385.
13. Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging 1993;3:335-348.
14. Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: Their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol 2006;148:565-578.
15. Staskin DR, Zoltan E. Anticholinergics and central nervous system effects: Are we confused? Rev Urol 2007;9:191-196.
16. Ditropan XL. (oxybutynin chloride extended release tablets) Prescribing information. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc; 2009.
17. Detrol LA. (tolterodine tartrate extended release capsules) Prescribing information. New York, NY: Pfizer, Inc; 2008.
18. Sanctura XR. (trospium chloride extended release capsules) Prescribing information. Irvine, CA: Allergan, Inc; 2008.
19. Enablex (darifenacin extended-release tablets): Prescribing information. East Hanover, NJ: Novartis; 2008.
20. VESIcare (solifenacin succinate tablets) Prescribing information. Deerfield, IL and Research Triangle Park, NC: Astellas Pharma US Inc. and GlaxoSmithKline; 2008.
21. Toviaz (fesoterodine fumarate): Prescribing information. New York, NY: Pfizer, Inc; 2008.
22. Oxytrol (oxybutynin transdermal system) Prescribing information. Corona, CA: Watson Pharmaceuticals, Inc; 2006.
23. Gelnique (oxybutynin chloride gel) Prescribing information. Corona, CA: Watson Pharmaceuticals, Inc; 2009.
24. Ditropan (oxybutynin chloride tablets and syrup) Prescribing information. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc; 2008.
25. Detrol (tolterodine tartrate tablets) Prescribing information. New York, NY: Pfizer, Inc; 2008.
26. Sanctura (trospium chloride 20 mg tablets) Prescribing information. Irvine, CA: Allergan, Inc; 2008.
27. Doroshyenko O, Jetter A, Odenthal KP, Fuhr U. Clinical pharmacokinetics of trospium chloride. Clin Pharmacokinet 2005;44:701-720.
28. Nilvebrant L, Pahlman I, D'Argy R. Tissue distribution of tolterodine and its metabolites: Low penetration into the central nervous system. Eur Urol 2000;84.
29. Nilvebrant L, Gillberg PG, Sparf B. Antimuscarinic potency and bladder selectivity of PNU-200577, a major metabolite of tolterodine. Pharmacol Toxicol 1997;81:169-172.
30. Maniscalco M, Singh-Franco D, Wolowich WR, Torres-Colon R. Solifenacin succinate for the treatment of symptoms of overactive bladder. Clin Ther 2006;28:1247-1272.
31. Ney P, Pandita RK, Newgreen DT, Breidenbach A, Stohr T, Andersson KE. Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo. BJU Int 2008;101:1036-1042.
32. Malhotra B, Gandelman K, Sachse R, Wood N, Michel MC. The design and development of fesoterodine as a prodrug of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of tolterodine. Curr Med Chem 2009;16:4481-4489.
33. Pak RW, Petrou SP, Staskin DR. Trospium chloride: A quaternary amine with unique pharmacologic properties. Curr Urol Rep 2003;4:436-440.
34. Ellsworth P, Kirshenbaum E. Update on the pharmacologic management of overactive bladder: The present and the future. Urol Nurs 2010;30:29-39, 53.
35. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006;7:41-53.
36. Deeken JF, Loscher W. The blood-brain barrier and cancer: Transporters, treatment, and Trojan horses. Clin Cancer Res 2007;13:1663-1674.
37. Golden PL, Pollack GM. Blood-brain barrier efflux transport. J Pharm Sci 2003;92:1739-1753.
38. Bauer B, Hartz AM, Fricker G, Miller DS. Modulation of p-glycoprotein transport function at the blood-brain barrier. Exp Biol Med (Maywood) 2005;230:118-127.
39. El-Bacha RS, Minn A. Drug metabolizing enzymes in cerebrovascular endothelial cells afford a metabolic protection to the brain. Cell Mol Biol (Noisy-le-grand) 1999;45:15-23.
40. Kay GG, Ebinger U. Preserving cognitive function for patients with overactive bladder: Evidence for a differential effect with darifenacin. Int J Clin Pract 2008;62:1792-1800.
41. Tanaka E. In vivo age-related changes in hepatic drug-oxidizing capacity in humans. J Clin Pharm Ther 1998;23:247-255.
42. Sandage B, Lerch G, Larsen G, Profy A. Trospium chloride does not cross the blood-brain barrier of male Long Evans rats. Neurology 2009;72(Suppl 3):A50.
43. Geyer J, Gavrilova O, Petzinger E. The role of p-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic overactive bladder drug trospium chloride. Drug Metab Dispos 2009;37:1371-1374.
44. Geyer J, Gavrilova O, Schwantes U. Differences in the brain penetration of the anticholinergic drugs trospium chloride and oxybutynin. UroToday Int J 2010;3, doi:.
45. Rovner ES. Trospium chloride in the management of overactive bladder. Drugs 2004;64:2433-2446.
46. Chancellor MB, de Miguel F. Treatment of overactive bladder: Selective use of anticholinergic agents with low drug-drug interaction potential. Geriatrics 2007;62:15-24.
47. Kay G, Malhotra B, Michel MC. Assessment of central nervous system access of a new antimuscarinic drug, fesoterodine. J Urol 2009;181(Suppl):84.
48. Starr JM, Wardlaw J, Ferguson K, MacLullich A, Deary IJ, Marshall I. Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2003;74:70-76.
49. Farrall AJ, Wardlaw JM. Blood-brain barrier: Ageing and microvascular disease-systematic review and meta-analysis. Neurobiol Aging 2009;30:337-352.
50. Andersson KE. Potential benefits of muscarinic M3 receptor selectivity. Eur Urol Suppl 2002;1:23-28.
51. Klausner AP, Steers WD. Antimuscarinics for the treatment of overactive bladder: A review of central nervous system effects. Curr Urol Rep 2007;8:441-447.
52. Gulsun M, Pinar M, Sabanci U. Psychotic disorder induced by oxybutynin: Presentation of two cases. Clin Drug Investig 2006;26:603-606.
53. Tsao JW, Heilman KM. Transient memory impairment and hallucinations associated with tolterodine use. N Engl J Med 2003;349:2274-2275.
54. Edwards KR, O'Connor JT. Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors. J Am Geriatr Soc 2002;50:1165-1166.
55. Donnellan CA, Fook L, McDonald P, Playfer JR. Oxybutynin and cognitive dysfunction. BMJ 1997;315:1363-1364.
56. Salvatore S, Serati M, Cardozo L, Uccella S, Bolis P. Cognitive dysfunction with tolterodine use. Am J Obstet Gynecol 2007;197:e8.
57. Womack KB, Heilman KM. Tolterodine and memory: dry but forgetful. Arch Neurol 2003;60:771-773.
58. Rabins PV, Blacker D, Rovner BW, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. 2nd edition. Am J Psychiatry 2007;164:5-56.
59. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006:CD005593, doi:.
60. Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: Evidence review for a clinical practice guideline. Ann Intern Med 2008;148:379-397.
61. Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: A systematic review and meta-analysis. Clin Interv Aging 2008;3:211-225.
62. Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: Longitudinal cohort study. BMJ 2006;332:455-459.
63. 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;53:2195-2201.
64. Kay GG, Granville LJ. Antimuscarinic agents: Implications and concerns in the management of overactive bladder in the elderly. Clin Ther 2005;27:127-138; quiz 139-140.
65. Scheife R, Takeda M. Central nervous system safety of anticholinergic drugs for the treatment of overactive bladder in the elderly. Clin Ther 2005;27:144-153.
66. 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;50:799-807.
67. Foote J, Glavind K, Kralidis G, Wyndaele JJ. Treatment of overactive bladder in the older patient: Pooled analysis of three phase III studies of darifenacin, an M3 selective receptor antagonist. Eur Urol 2005;48:471-477.
68. Sand PK, Johnson TM II, 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;107:612-620.
69. Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol 2006;50:317-326.
70. Pietzko A, Dimpfel W, Schwantes U, Topfmeier P. Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. Eur J Clin Pharmacol 1994;47:337-343.
71. Todorova A, Vonderheid-Guth B, Dimpfel W. Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol 2001;41:636-644.
72. Katz IR, Sands LP, Bilker W, DiFilippo S, Boyce A, D'Angelo K. Identification of medications that cause cognitive impairment in older people: The case of oxybutynin chloride. J Am Geriatr Soc 1998;46:8-13.
73. 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;8:615-626.
74. Kay GG, Wesnes KA. Pharmacodynamic effects of darifenacin, a muscarinic M selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers. BJU Int 2005;96:1055-1062.
75. Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: Effects of darifenacin. J Urol 2005;173:493-498.
76. Staskin D, Kay G, Tannenbaum C, et al. 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;64:1294-1300.
77. Staskin D, Kay G, Tannenbaum C, et al. Trospium chloride is undetectable in the older human central nervous system (CNS). J Am Geriatr Soc 2010;58:1618-1619.
78. Diefenbach K, Arold G, Wollny A, Schwantes U, Haselmann J, Roots I. Effects on sleep of anticholinergics used for overactive bladder treatment in healthy volunteers aged > or = 50 years. BJU Int 2005;95:346-349.
79. Diefenbach K, Donath F, Maurer A, et al. Randomised, double-blind study of the effects of oxybutynin, tolterodine, trospium chloride and placebo on sleep in healthy young volunteers. Clin Drug Investig 2003;23:395-404.
80. Staskin DR, Harnett MD. Effect of trospium chloride on somnolence and sleepiness in patients with overactive bladder. Curr Urol Rep 2004;5:423-426.
81. Herberg K, Fusgen I. Influence of trospium chloride, oxybutynin HCL and propiverine HCl on performances having relevance for safety. Geriat Fersch 1997;7:77-82.
82. Herberg K. Safety in everyday situations and street traffic with the use of medication for incontinence: New investigations into the safety and potential of urological anticholinergic drugs. Die Medizinsche Welt 1999;50:217-222.
83. Brown JS, Vittinghoff E, Wyman JF, et al. Urinary incontinence: Does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc 2000;48:721-725.
84. Nebes RD, Pollock BG, Halligan EM, Kirshner MA, Houck PR. Serum anticholinergic activity and motor performance in elderly persons. J Gerontol A Biol Sci Med Sci 2007;62:83-85.
85. Darkow T, Fontes CL, Williamson TE. Costs associated with the management of overactive bladder and related comorbidities. Pharmacotherapy 2005;25:511-519.
86. Wagner TH, Hu TW, Bentkover J, et al. Health-related consequences of overactive bladder. Am J Manag Care 2002;8:S598-S607.