Antimuscarinics for the treatment of overactive bladder: A review of central nervous system effects

Current Urology Reports

Volumn 8, Issue 6, 2007, Pages 441-447

  Klausner, Adam P ^a   Steers, William D ^b  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

AMITRIPTYLINE; BENZATROPINE; DARIFENACIN; HYOSCYAMINE; IMIPRAMINE; KETOCONAZOLE; MUSCARINIC RECEPTOR; MUSCARINIC RECEPTOR BLOCKING AGENT; ORPHENADRINE; OXYBUTYNIN; PLACEBO; SOLIFENACIN; TOLTERODINE; TRIHEXYPHENIDYL; TROSPIUM CHLORIDE;

AGITATION; ALZHEIMER DISEASE; AMNESIA; ANXIETY; ASTHENIA; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; COGNITIVE DEFECT; CONFUSION; DELIRIUM; DEPRESSION; DISORIENTATION; DIZZINESS; DROWSINESS; DRUG DOSE ESCALATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG RELEASE; ELECTROENCEPHALOGRAM; FATIGUE; HALLUCINATION; HEADACHE; HUMAN; INSOMNIA; MEMORY DISORDER; NERVOUSNESS; NONHUMAN; OVERACTIVE BLADDER; PATIENT CARE; POLYSOMNOGRAPHY; PSYCHOSIS; REM SLEEP; REVIEW; SIDE EFFECT; SOMNOLENCE; STUPOR; SYNCOPE;

ADULT; AGE DISTRIBUTION; AGED; CENTRAL NERVOUS SYSTEM DISEASES; CHILD; COGNITION DISORDERS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; INCIDENCE; MALE; MUSCARINIC ANTAGONISTS; PROGNOSIS; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; SEX DISTRIBUTION; URINARY BLADDER, OVERACTIVE; URODYNAMICS;

EID: 36349016565     PISSN: 15272737     EISSN: 15346285     Source Type: Journal    
DOI: 10.1007/s11934-007-0046-0     Document Type: Review

References (45)

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. Temml C, Heidler S, Ponholzer A, Madersbacher S: Prevalence of the overactive bladder syndrome by applying the International Continence Society definition. Eur Urol 2005, 48:622-627.
3. 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.
4. Coyne KS, Zhou Z, Thompson C, Versi E: The impact on health-related quality of life of stress, urge and mixed urinary incontinence. BJU Int 2003, 92:731-735.
5. Darkow T, Fontes CL, Williamson TE: Costs associated with the management of overactive bladder and related comorbidities. Pharmacotherapy 2005, 25:511-519.
6. Nabi G, Cody JD, Ellis G, et al.: Anticholinergic drugs versus placebo for overactive bladder syndrome in adults. Cochrane Database Syst Rev 2006, CD003781. Meta-analysis providing an updated review of the efficacy and safety of commonly used antimuscarinic agents for the treatment of overactive bladder. The results show that antimuscarinics improve symptoms in patients with overactive bladder; however, the clinical significance of this improvement is not great.
7. Sanctura (trospium chloride) 20 mg tablets prescribing information. Available at http://www.sanctura.com/pdf/sanctura_pi.pdf. Accessed February 1, 2007.
8. Detrol LA tolterodine tartrate extended release capsules: prescribing information. Available at http://www.detrolla.com/cwpb/appmanager/detrolLA/ detrolLADesktop?_nfpb=true&_pageLabel=detrolLA_prescribingInformation. Accessed February 1, 2007.
9. Irwin DE, Milsom I, Hunskaar 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, 50:1306-1314, discussion 1314-1315.
10. Fick DM, Cooper JW, Wade WE, et al.: Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med 2003, 163:2716-2724.
11. Scarpero HM, Dmochowski RR: Muscarinic receptors: what we know. Curr Urol Rep 2003, 4:421-428.
12. 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. Provides a comprehensive review of muscarinic receptor activity and function according to different organ systems.
13. Yamada M, Miyakawa T, Duttaroy A, et al.: Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature 2001, 410:207-212.
14. Haab F, Stewart L, Dwyer P: Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol 2004, 45:420-429, discussion 429.
15. Garely AD, Kaufman JM, Sand PK, et al.: Symptom bother and health-related quality of life outcomes following solifenacin treatment for overactive bladder: the VESIcare Open-Label Trial (VOLT). Clin Ther 2006, 28:1935-1946.
16. Cardozo L, Lisec M, Millard R, et al.: Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J Urol 2004, 172:1919-1924.
17. Napier C, Gupta P: Darifenacin is selective for the human recombinant M3 receptor subtype [abstract 445]. Presented at the International Continence Society annual meeting. Heidelberg, Germany; August 28-30, 2002.
18. Ikeda K, Kobayashi S, Suzuki M, et al.: M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. Naunyn Schmiedebergs Arch Pharmacol 2002, 366:97-103.
19. Appell RA, Sand P, Dmochowski R, et al.: Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study. Mayo Clin Proc 2001, 76:358-363.
20. Van Kerrebroeck P, Kreder K, Jonas U, et al.: Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology 2001, 57:414-421.
21. 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. This article shows not only that oxybutynin has more profound effects than darifenacin on memory in elderly individuals but also that the most significant deficits occur with delayed recall. More importantly, subjects were unaware of memory deficits. This point should alert readers to be skeptical when evaluating studies in which patient self-reports are the sole means used to categorize CNS side effects of antimuscarinic therapies.
22. Sugiyama T, Park YC, Kurita T: Oxybutynin disrupts learning and memory in the rat passive avoidance response. Urol Res 1999, 27:393-395.
23. Womack KB, Heilman KM: Tolterodine and memory: dry but forgetful. Arch Neurol 2003, 60:771-773.
24. Tanaka E: In vivo age-related changes in hepatic drug-oxidizing capacity in humans. J Clin Pharm Ther 1998, 23:247-255.
25. Gulsun M, Pinar M, Sabanci U: Psychotic disorder induced by oxybutynin: presentation of two cases. Clin Drug Investig 2006, 26:603-606.
26. Tsao JW, Heilman KM: Transient memory impairment and hallucinations associated with tolterodine use. N Engl J Med 2003, 349:2274-2275.
27. Partridge JG, Apparsundaram S, Gerhardt GA, et al.: Nicotinic acetylcholine receptors interact with dopamine in induction of striatal long-term depression. J Neurosci 2002, 22:2541-2549.
28. 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.
29. Once-a-day Ditropan XL (oxybutynin chloride) extended-release tablets 5, 10, 15 mg. Full U.S. prescribing information. Available at http://www.ditropanxl.com/html/pdxl/prescribing_consumer.jsp;jsessionid= UYLZTKGIQK2EOCQPCCFTC0YKB2IIQNSC? Accessed February 1, 2007.
30. Dmochowski RR, Nitti V, Staskin D, et al.: Transdermal oxybutynin in the treatment of adults with overactive bladder: combined results of two randomized clinical trials. World J Urol 2005, 23:263-270.
31. Enablex (darifenacin) extended release tablets: prescribing information. Available at http://www.enablex.com/info/ tools/pi.jsp. Accessed February 1, 2007.
32. VESIcare (solifenacin succinate) tablets. Available at http://www.astellas.us/docs/vesicare.pdf. Accessed February 1, 2007.
33. Diefenback K, Donath F, Maurer A, et al.: Randomized, double-blind study of the effects of oxybutynin, tolterodine, trospium chloride and placebo on sleep in heathy young volunteers. Clin Drug Investig 2003, 23:395-404. Available at http://druginvestigation.adisonline.com.
34. Ancelin ML, Artero S, Portet F, et al.: Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006, 332:455-459. This paper provides evidence that use of antimuscarinic agents is a strong risk factor for cognitive impairment in elderly individuals. The lack of progression to frank dementia noted in the study suggests that the effects may be reversible.
35. Erdincler P, Tuzgen S, Erdincler UD, et al.: Influence of aging on blood-brain barrier permeability and free radical formation following experimental brain cold injury. Acta Neurochir (Wien) 2002, 144:195-199, discussion 199-200.
36. Abdel-Rahman A, Shetty AK, Abou-Donia MB: Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome. Neurobiol Dis 2002, 10:306-326.
37. Sommer BR, O'Hara R, Askari N, et al.: The effect of oxybutynin treatment on cognition in children with diurnal incontinence. J Urol 2005, 173:2125-2127.
38. Blennow K, de Leon MJ, Zetterberg H: Alzheimer's disease. Lancet 2006, 368:387-403. This paper provides a comprehensive and up-to-date review of Alzheimer's disease. Epidemiology, pathophysiology, and treatment are covered in detail.
39. Siegler EL, Reidenberg M: Treatment of urinary incontinence with anticholinergics in patients taking Cholinesterase inhibitors for dementia. Clin Pharmacol Ther 2004, 75:484-488.
40. Perry EK, Kilford L, Lees AJ, et al.: Increased Alzheimer pathology in Parkinson's disease related to antimuscarinic drugs. Ann Neurol 2003, 54:235-238.
41. Garcia-Alloza M, Robbins EM, Zhang-Nunes SX, et al.: Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis 2006, 24:516-524.
42. Jankowsky JL, Xu G, Fromholt D, et al.: Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease. J Neuropathol Exp Neurol 2003, 62:1220-1227.
43. Klausner AP, Fletcher S, Yang SK, et al.: Does oxybutynin alter amyloid beta peptides in a mouse model of Alzheimer's Disease? [abstract]. J Urol 2005, 173:41.
44. Sharma S, Klausner AP, Fletcher S, et al.: The effect of oxybutynin on plaques, amyloid beta peptides, and behavior in mouse and human cybrid models of Alzheimer's Disease [abstract]. J Urol 2006, 175:55.
45. Daniel JM, Hulst JL, Lee CD: Role of hippocampal M2 muscarinic receptors in the estrogen-induced enhancement of working memory. Neuroscience 2005, 132:57-64.