Overactive Bladder Medication
- Author: Pamela I Ellsworth, MD, FACS; Chief Editor: Edward David Kim, MD, FACS more...
Medication Summary
The goals of pharmacotherapy are to improve OAB symptoms, reduce morbidity, and prevent complications. Anticholinergics are the first-line agents used to treat overactive bladder (OAB). Individuals with genital atrophy may benefit from topical estrogen therapy, and, in select cases of refractory OAB, tricyclic antidepressants may be helpful.
Anticholinergics
Class Summary
Anticholinergics inhibit the binding of acetylcholine to the muscarinic receptor in the detrusor, thereby suppressing involuntary bladder contractions. They are associated with an increase in bladder volume voided, as well as a decrease in micturition frequency and sensation of urgency.
Angioedema of the face, lips, tongue, and/or pharynx has been noted in several of these agents in postmarketing surveillance, including solifenacin, darifenacin, trospium chloride, and fesoterodine. Warnings are noted in the prescribing information for these agents, and if patients experience such symptoms they should seek emergency care.
Oxybutynin (Ditropan, Ditropan XL, Oxytrol, Gelnique)
Oxybutynin inhibits the action of acetylcholine on smooth muscle and has a direct antispasmodic effect on smooth muscles. This, in turn, increases bladder capacity and decreases uninhibited contractions. Oxybutynin is relatively M3, M1 specific.
Tolterodine (Detrol, Detrol LA)
Tolterodine is a nonspecific competitive muscarinic receptor antagonist for OAB. However, it differs from other anticholinergic types in that it has selectivity for urinary bladder over salivary glands. Tolterodine exhibits a high specificity for muscarinic receptors. It has minimal activity or affinity for other neurotransmitter receptors and other potential targets, such as calcium channels.
Trospium (Sanctura)
Trospium is a nonspecific quaternary ammonium compound that is excreted intact in the urine and thus is not dependent on the cytochrome P450 system for its metabolism. Being a quarternary amine, it is less likely to penetrate the blood-brain barrier. It antagonizes acetylcholine's effect on muscarinic receptors. Its parasympathetic effect reduces smooth-muscle tone in the bladder. Trospium is indicated to treat symptoms of OAB (eg, urinary incontinence, urgency, frequency). It is available as a single dose, and the extended release formulation should not be taken at night.
Darifenacin (Enablex)
Darifenacin is an extended-release product that elicits competitive muscarinic receptor antagonistic activity. It reduces bladder smooth-muscle contractions. It has high affinity for the M3 receptors and less affinity for other muscarinic receptors. Darifenacin is indicated for OAB with symptoms of urge incontinence, urgency and frequency. Swallow it whole; do not chew, divide, or crush it.
Solifenacin (Vesicare)
Solifenacin is a competitive muscarinic-receptor antagonist that was approved by the US Food and Drug Administration (FDA) in late 2004 for the treatment of OAB with symptoms of urge incontinence, urgency, and urinary frequency. It shares a similar muscarinic receptor affinity as oxybutyinin and is available in 2 doses.
Fesoterodine (Toviaz)
Fesoterodine is the most recent anticholinergic agent to be approved. It is available in 2 doses, and the 8-mg dose has been shown to be superior to tolterodine (Detrol LA) 4mg in the reduction of UUI episodes. It shares a similar muscarinic receptor affinity as tolterodine.
Tricyclic antidepressants
Class Summary
Tricyclic antidepressants that have been used to treat OAB include imipramine and doxepin. Some agents of this type may decrease bladder contractility. They are not indicated for the first-line treatment of OAB.
Imipramine (Tofranil)
Imipramine is useful in facilitating urine storage. It decreases bladder contractility and increases outlet resistance.
Doxepin (Sinequan)
Doxepin increases the concentration of serotonin and norepinephrine in the central nervous system (CNS) by inhibiting their reuptake by presynaptic neuronal membrane. These effects are associated with a decrease in symptoms of depression.
Hormones
Class Summary
Hormones are used to treat OAB in association with atrophic urethritis and are not recommended as first-line therapies for OAB.
Estrogen (Premarin)
Detrusor overactivity can be associated with atrophic urethritis; topical application of estrogen vaginal cream should be considered in women with symptomatic atrophic urethritis/vaginits.
Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, 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(2):167-78. [Medline].
Woodhouse JB, Patki P, Patil K, Shah J. Botulinum toxin and the overactive bladder. Br J Hosp Med (Lond). Sep 2006;67(9):460-4. [Medline].
Wein AJ, Rackley RR. Overactive bladder: a better understanding of pathophysiology, diagnosis and management. J Urol. Mar 2006;175(3 Pt 2):S5-10. [Medline].
Morrison J, Steers WD, Brading AF, et al. Neurophysiology and neuropharmacology. In: Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence. 2nd ed. Plymouth, England: Health Publications; 2002:86-163.
Yoshimura N, Chancellor MB. Current and future pharmacological treatment for overactive bladder. J Urol. Nov 2002;168(5):1897-913. [Medline].
de Groat WC. The urothelium in overactive bladder: passive bystander or active participant?. Urology. Dec 2004;64(6 Suppl 1):7-11. [Medline].
Andersson KE, Hedlund P. Pharmacologic perspective on the physiology of the lower urinary tract. Urology. Nov 2002;60(5 Suppl 1):13-20; discussion 20-1. [Medline].
DuBeau CE. Interpreting the effect of common medical conditions on voiding dysfunction in the elderly. Urol Clin North Am. Feb 1996;23(1):11-8. [Medline].
Miller SW. Management and treatment of overactive bladder in the elderly. J Am Soc Consult Pharm. 1999;14(Suppl 4):S1-S11.
Shah D, Badlani G. Treatment of overactive bladder and incontinence in the elderly. Rev Urol. 2002;4 Suppl 4:S38-43. [Medline]. [Full Text].
Staskin DR. Overactive bladder in the elderly: a guide to pharmacological management. Drugs Aging. 2005;22(12):1013-28. [Medline].
Stoddart H, Donovan J, Whitley E, Sharp D, Harvey I. Urinary incontinence in older people in the community: a neglected problem?. Br J Gen Pract. Jul 2001;51(468):548-52. [Medline]. [Full Text].
Voytas J. The role of geriatricians and family practitioners in the treatment of overactive bladder and incontinence. Rev Urol. 2002;4 Suppl 4:S44-9. [Medline]. [Full Text].
Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. May 2003;20(6):327-36. [Medline].
Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int. Jun 2001;87(9):760-6. [Medline].
Abrams P, Kelleher CJ, Kerr LA, Rogers RG. Overactive bladder significantly affects quality of life. Am J Manag Care. Jul 2000;6(11 Suppl):S580-90. [Medline].
Davila GW, Neimark M. The overactive bladder: prevalence and effects on quality of life. Clin Obstet Gynecol. Mar 2002;45(1):173-81. [Medline].
Hu TW, Wagner TH, Bentkover JD, LeBlanc K, Piancentini A, Stewart WF, et al. Estimated economic costs of overactive bladder in the United States. Urology. Jun 2003;61(6):1123-8. [Medline].
Liberman JN, Hunt TL, Stewart WF, Wein A, Zhou Z, Herzog AR, et al. Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey. Urology. Jun 2001;57(6):1044-50. [Medline].
Bailey KL, Torigoe Y, Zhou S, et al. Overactive bladder cost of illness: Analysis of Medi-Cal claims. Presented at the International Society for Pharmacoeconomics and Outcomes Research 5th Annual International meeting,. Arlington, VA. May 21-24, 2000.
Brown JS, Vittinghoff E, Wyman JF, Stone KL, Nevitt MC, Ensrud KE, et al. Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc. Jul 2000;48(7):721-5. [Medline].
Weiss JP, Blaivas JG, Bliwise DL, Dmochowski RR, Dubeau CE, Lowe FC, et al. The evaluation and treatment of nocturia: a consensus statement. BJU Int. Jul 2011;108(1):6-21. [Medline].
Dmochowski RR. Treatment of the overactive bladder: where we stand in 2003. Rev Urol. 2003;5 Suppl 8:S11-7. [Medline]. [Full Text].
Kirby M, Artibani W, Cardozo L, Chapple C, Diaz DC, De Ridder D, et al. Overactive bladder: The importance of new guidance. Int J Clin Pract. Oct 2006;60(10):1263-71. [Medline].
Lai HH, Boone TB, Appell RA. Selecting a medical therapy for overactive bladder. Rev Urol. 2002;4 Suppl 4:S28-37. [Medline]. [Full Text].
Lee M, Weberski J. Options for treatment of overactive bladder. J Am Pharm Assoc. July 2005;(;(Suppl):S1-S15.
Ouslander JG. Management of overactive bladder. N Engl J Med. Feb 19 2004;350(8):786-99. [Medline].
[Best Evidence] 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. Oct 18 2006;CD003193. [Medline].
Lackner TE. Pharmacotherapy of urinary incontinence. J Am Med Dir Assoc. Jan-Feb 2002;3(1 Suppl):S16-24. [Medline].
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. Apr 19 2003;326(7394):841-4. [Medline]. [Full Text].
Lepor H. A comparison of anticholinergic therapies in the treatment of overactive bladder. Rev Urol. Fall 2001;3(4):209. [Medline]. [Full Text].
MacDiarmid SA. Overactive bladder: improving the efficacy of anticholinergics by dose escalation. Curr Urol Rep. Dec 2003;4(6):446-51. [Medline].
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. Oct 18 2006;CD003781. [Medline].
Lee YS, Choo MS, Lee JY, et al. Symptom change after discontinuation of successful antimuscarinic treatment in patients with overactive bladder symptoms: a randomised, multicentre trial. Int J Clin Pract. Sep 2011;65(9):997-1004. [Medline].
Tapp AJ, Cardozo LD, Versi E, Cooper D. The treatment of detrusor instability in post-menopausal women with oxybutynin chloride: a double blind placebo controlled study. Br J Obstet Gynaecol. Jun 1990;97(6):521-6. [Medline].
Roberts RG, Garely AD, Bavendam T. Safety and tolerability of tolterodine for the treatment of overactive bladder in adults. Am J Manag Care. Jul 2005;11(4 Suppl):S158-62. [Medline].
Abrams P. Evidence for the efficacy and safety of tolterodine in the treatment of overactive bladder. Expert Opin Pharmacother. Oct 2001;2(10):1685-701. [Medline].
Kanofsky JA, Nitti VW. Tolterodine for treatment of overactive bladder. Urol Clin North Am. Nov 2006;33(4):447-53, viii. [Medline].
Diokno AC, Appell RA, Sand PK, Dmochowski RR, Gburek BM, Klimberg IW, et al. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc. Jun 2003;78(6):687-95. [Medline].
Gupta SK, Sathyan G. Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin. J Clin Pharmacol. Mar 1999;39(3):289-96. [Medline].
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. May 2002;50(5):799-807. [Medline].
Burgio KL, Goode PS, Johnson TM, et al. Behavioral Versus Drug Treatment for Overactive Bladder in Men: The Male Overactive Bladder Treatment in Veterans (MOTIVE) Trial. J Am Geriatr Soc. Dec 2011;59(12):2209-16. [Medline].
Staskin DR. Trospium chloride: Distinct among other anticholinergic agents available for the treatment of overactive bladder. Urol Clin North Am. Nov 2006;33(4):465-73, viii. [Medline].
Zinner NR. Trospium chloride: an anticholinergic quaternary ammonium compound for the treatment of overactive bladder. Expert Opin Pharmacother. Jul 2005;6(8):1409-20. [Medline].
Brunton S, Kuritzky L. Recent developments in the management of overactive bladder: focus on the efficacy and tolerability of once daily solifenacin succinate 5 mg. Curr Med Res Opin. Jan 2005;21(1):71-80. [Medline].
Kelleher CJ, Cardozo L, Chapple CR, Haab F, Ridder AM. Improved quality of life in patients with overactive bladder symptoms treated with solifenacin. BJU Int. Jan 2005;95(1):81-5. [Medline].
Maniscalco M, Singh-Franco D, Wolowich WR, Torres-Colón R. Solifenacin succinate for the treatment of symptoms of overactive bladder. Clin Ther. Sep 2006;28(9):1247-72. [Medline].
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. Mar 2006;4(1):14-24. [Medline].
Zinner N, Susset J, Gittelman M, Arguinzoniz M, Rekeda L, Haab F. Efficacy, tolerability and safety of darifenacin, an M(3) selective receptor antagonist: an investigation of warning time in patients with OAB. Int J Clin Pract. Jan 2006;60(1):119-26. [Medline].
Herschorn S, Swift S, Guan Z, et al. Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial. BJU Int. Jan 2010;105(1):58-66. [Medline].
Chapple CR, Yamanishi T, Chess-Williams R. Muscarinic receptor subtypes and management of the overactive bladder. Urology. Nov 2002;60(5 Suppl 1):82-8; discussion 88-9. [Medline].
Michel MC, Hegde SS. Treatment of the overactive bladder syndrome with muscarinic receptor antagonists: a matter of metabolites?. Naunyn Schmiedebergs Arch Pharmacol. Nov 2006;374(2):79-85. [Medline].
Dmochowski RR. Duloxetine: a summary of published clinical experience. Rev Urol. 2004;6 Suppl 3:S56-63. [Medline]. [Full Text].
Burgio KL. Influence of behavior modification on overactive bladder. Urology. Nov 2002;60(5 Suppl 1):72-6; discussion 77. [Medline].
Wilson PD, Berghmans B, Hagen S, et al. Adult conservative management. In: Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence Management. Paris, France.: Health Publications; 2005:855-94.
Cardozo L, Stanton SL, Hafner J, Allan V. Biofeedback in the treatment of detrusor instability. Br J Urol. Jun 1978;50(4):250-4. [Medline].
Cardozo LD, Abrams PD, Stanton SL, Feneley RC. Idiopathic bladder instability treated by biofeedback. Br J Urol. Dec 1978;50(7):521-3. [Medline].
Burgio KL, Whitehead WE, Engel BT. Urinary incontinence in the elderly. Bladder-sphincter biofeedback and toileting skills training. Ann Intern Med. Oct 1985;103(4):507-15. [Medline].
Consensus conference. Urinary incontinence in adults. JAMA. May 12 1989;261(18):2685-90. [Medline].
Fantl JA, Newman DK, Colling J, et al. Urinary Incontinence in Adults: Acute and Chronic Management Clinical Practice Guidelines. No. 2, 1996 Update. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; March 1996.
Burgio KL, Locher JL, Goode PS, Hardin JM, McDowell BJ, Dombrowski M, et al. Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAMA. Dec 16 1998;280(23):1995-2000. [Medline].
Fantl JA, Wyman JF, McClish DK, Harkins SW, Elswick RK, Taylor JR, et al. Efficacy of bladder training in older women with urinary incontinence. JAMA. Feb 6 1991;265(5):609-13. [Medline].
Burgio KL, Locher JL, Goode PS. Combined behavioral and drug therapy for urge incontinence in older women. J Am Geriatr Soc. Apr 2000;48(4):370-4. [Medline].
Wyman JF, Fantl JA, McClish DK, Bump RC. Comparative efficacy of behavioral interventions in the management of female urinary incontinence. Continence Program for Women Research Group. Am J Obstet Gynecol. Oct 1998;179(4):999-1007. [Medline].
Wyman JF, Fantl JA. Bladder training in ambulatory care management of urinary incontinence. Urol Nurs. Sep 1991;11(3):11-7. [Medline].
Burgio KL, Goode PS, Locher JL, Umlauf MG, Roth DL, Richter HE, et al. Behavioral training with and without biofeedback in the treatment of urge incontinence in older women: a randomized controlled trial. JAMA. Nov 13 2002;288(18):2293-9. [Medline].
Burton JR, Pearce KL, Burgio KL, Engel BT, Whitehead WE. Behavioral training for urinary incontinence in elderly ambulatory patients. J Am Geriatr Soc. Aug 1988;36(8):693-8. [Medline].
McDowell BJ, Burgio KL, Dombrowski M, Locher JL, Rodriguez E. An interdisciplinary approach to the assessment and behavioral treatment of urinary incontinence in geriatric outpatients. J Am Geriatr Soc. Apr 1992;40(4):370-4. [Medline].
Andersson KE. New pharmacologic targets for the treatment of the overactive bladder: an update. Urology. Mar 2004;63(3 Suppl 1):32-41. [Medline].
Chancellor MB. New frontiers in the treatment of overactive bladder and incontinence. Rev Urol. 2002;4 Suppl 4:S50-6. [Medline]. [Full Text].
Epstein BJ, Gums JG, Molina E. Newer agents for the management of overactive bladder. Am Fam Physician. Dec 15 2006;74(12):2061-8. [Medline].
Monaghan C. Pharmacological treatment of urinary incontinence: Current and future management options. Clin Excell Nurse Pract. 2004;8(3):121-5.
Ng CK, Gonzalez RR, Te AE. Refractory overactive bladder in men: update on novel therapies. Curr Urol Rep. Nov 2006;7(6):456-61. [Medline].
Khan S, Game X, Kalsi V, Gonzales G, Panicker J, Elneil S, et al. Long-term effect on quality of life of repeat detrusor injections of botulinum neurotoxin-a for detrusor overactivity in patients with multiple sclerosis. J Urol. Apr 2011;185(4):1344-9. [Medline].

