Overactive Bladder Medication
- Author: Pamela I Ellsworth, MD; Chief Editor: Edward David Kim, MD, FACS more...
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 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 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 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 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 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 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 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.
These agents elicit a direct inhibition of afferent nerve firing independent of the relaxing effects on bladder smooth muscle.
Mirabegron is a beta-3 adrenergic receptor agonist that causes relaxation of the detrusor smooth muscle of the urinary bladder and increases bladder capacity. It is indicated for overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Neuromuscular Blockers, Botulinum Toxins
Detrusor injections of botulinum neurotoxin type A may be considered for adults with OAB who cannot use or do not adequately respond to anticholinergic medication.
OnabotulinumtoxinA is a neurotoxin derived from Clostridium botulinum. It prevents ACh release from presynaptic membrane, resulting in a temporary calming effect of muscle contractions by blocking the transmission of nerve impulses.
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 is useful in facilitating urine storage. It decreases bladder contractility and increases outlet resistance.
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 are used to treat OAB in association with atrophic urethritis and are not recommended as first-line therapies for OAB.
Detrusor overactivity can be associated with atrophic urethritis; topical application of estrogen vaginal cream should be considered in women with symptomatic atrophic urethritis/vaginits.
Brown T. Overactive bladder guidelines released. Medscape Medical News. October 26, 2012. Accessed November 14, 2012.
Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012/12. 188(6 suppl):2455-63. [Abstract]. [Full Text].
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].
Wein AJ, Rackley RR. Overactive bladder: a better understanding of pathophysiology, diagnosis and management. J Urol. 2006 Mar. 175(3 Pt 2):S5-10. [Medline].
Morrison J, Steers WD, Brading AF, et al. Neurophysiology and neuropharmacology. 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. 2002 Nov. 168(5):1897-913. [Medline].
de Groat WC. The urothelium in overactive bladder: passive bystander or active participant?. Urology. 2004 Dec. 64(6 Suppl 1):7-11. [Medline].
Andersson KE, Hedlund P. Pharmacologic perspective on the physiology of the lower urinary tract. Urology. 2002 Nov. 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. 1996 Feb. 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.
Staskin DR. Overactive bladder in the elderly: a guide to pharmacological management. Drugs Aging. 2005. 22(12):1013-28. [Medline].
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. 2003 May. 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. 2001 Jun. 87(9):760-6. [Medline].
Abrams P, Kelleher CJ, Kerr LA, Rogers RG. Overactive bladder significantly affects quality of life. Am J Manag Care. 2000 Jul. 6(11 Suppl):S580-90. [Medline].
Davila GW, Neimark M. The overactive bladder: prevalence and effects on quality of life. Clin Obstet Gynecol. 2002 Mar. 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. 2003 Jun. 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. 2001 Jun. 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. 2000 Jul. 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. 2011 Jul. 108(1):6-21. [Medline].
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. 2006 Oct. 60(10):1263-71. [Medline].
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. 2004 Feb 19. 350(8):786-99. [Medline].
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 Oct 18. CD003193. [Medline].
Lackner TE. Pharmacotherapy of urinary incontinence. J Am Med Dir Assoc. 2002 Jan-Feb. 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. 2003 Apr 19. 326(7394):841-4. [Medline]. [Full Text].
MacDiarmid SA. Overactive bladder: improving the efficacy of anticholinergics by dose escalation. Curr Urol Rep. 2003 Dec. 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. 2006 Oct 18. CD003781. [Medline].
Reynolds WS, McPheeters M, Blume J, Surawicz T, Worley K, Wang L, et al. Comparative Effectiveness of Anticholinergic Therapy for Overactive Bladder in Women: A Systematic Review and Meta-analysis. Obstet Gynecol. 2015 Jun. 125 (6):1423-32. [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. 2011 Sep. 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. 1990 Jun. 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. 2005 Jul. 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. 2001 Oct. 2(10):1685-701. [Medline].
Kanofsky JA, Nitti VW. Tolterodine for treatment of overactive bladder. Urol Clin North Am. 2006 Nov. 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. 2003 Jun. 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. 1999 Mar. 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. 2002 May. 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. 2011 Dec. 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. 2006 Nov. 33(4):465-73, viii. [Medline].
Zinner NR. Trospium chloride: an anticholinergic quaternary ammonium compound for the treatment of overactive bladder. Expert Opin Pharmacother. 2005 Jul. 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. 2005 Jan. 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. 2005 Jan. 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. 2006 Sep. 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. 2006 Mar. 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. 2006 Jan. 60(1):119-26. [Medline].
Doheny K. FDA OKs First OTC Remedy for Overactive Bladder. Available at http://www.medscape.com/viewarticle/778226. Accessed: February 5, 2013.
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. 2010 Jan. 105(1):58-66. [Medline].
Cardozo L, Amarenco G, Pushkar D, Mikulas J, Drogendijk T, Wright M, et al. Severity of overactive bladder symptoms and response to dose escalation in a randomized, double-blind trial of solifenacin (SUNRISE). BJU Int. 2013 May. 111(5):804-10. [Medline].
Chapple CR, Yamanishi T, Chess-Williams R. Muscarinic receptor subtypes and management of the overactive bladder. Urology. 2002 Nov. 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. 2006 Nov. 374(2):79-85. [Medline].
Chapple CR, Kaplan SA, Mitcheson D, et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a ß(3)-adrenoceptor agonist, in overactive bladder. Eur Urol. 2013 Feb. 63(2):296-305. [Medline].
Khullar V, Amarenco G, Angulo JC, et al. Efficacy and tolerability of mirabegron, a β3-adrenoceptor agonist, in patients with overactive bladder: Results from a randomised European-Australian phase 3 trial. Eur Urol. November 2012.
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. 2011 Apr. 185(4):1344-9. [Medline].
Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF, Menefee SA, et al. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med. 2012 Nov 8. 367(19):1803-13. [Medline]. [Full Text].
Burgio KL. Influence of behavior modification on overactive bladder. Urology. 2002 Nov. 60(5 Suppl 1):72-6; discussion 77. [Medline].
Wilson PD, Berghmans B, Hagen S, et al. Adult conservative management. 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. 1978 Jun. 50(4):250-4. [Medline].
Cardozo LD, Abrams PD, Stanton SL, Feneley RC. Idiopathic bladder instability treated by biofeedback. Br J Urol. 1978 Dec. 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. 1985 Oct. 103(4):507-15. [Medline].
Consensus conference. Urinary incontinence in adults. JAMA. 1989 May 12. 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. 1998 Dec 16. 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. 1991 Feb 6. 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. 2000 Apr. 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. 1998 Oct. 179(4):999-1007. [Medline].
Wyman JF, Fantl JA. Bladder training in ambulatory care management of urinary incontinence. Urol Nurs. 1991 Sep. 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. 2002 Nov 13. 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. 1988 Aug. 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. 1992 Apr. 40(4):370-4. [Medline].
Andersson KE. New pharmacologic targets for the treatment of the overactive bladder: an update. Urology. 2004 Mar. 63(3 Suppl 1):32-41. [Medline].
Epstein BJ, Gums JG, Molina E. Newer agents for the management of overactive bladder. Am Fam Physician. 2006 Dec 15. 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. 2006 Nov. 7(6):456-61. [Medline].
Zhang J, Cheng W, Cai M. Effects of electroacupuncture on overactive bladder refractory to anticholinergics: a single-blind randomised controlled trial. Acupunct Med. 2015 Jun 3. [Medline].
Bhide AA, Digesu GA, Fernando R, Khullar V. Use of mirabegron in treating overactive bladder. Int Urogynecol J. 2012 Mar 13. [Medline].
Chapple C, Sievert KD, Macdiarmid S, Khullar V, Radziszewski P, Nardo C, et al. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013 Aug. 64(2):249-56. [Medline].
Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, et al. Randomized Double-blind, Active-controlled Phase 3 Study to Assess 12-Month Safety and Efficacy of Mirabegron, a ß(3)-Adrenoceptor Agonist, in Overactive Bladder. Eur Urol. 2013 Feb. 63(2):296-305. [Medline].
Khullar V, Cambronero J, Stroberg P, Angulo J, Boerrigter P, Blauwet MB et al. The efficacy and tolerability of mirabegron in patients with overactive bladder - results from a European-Australian Phase III trial. Eur Urol. 2011. 10(2, suppl):278-279.
Lowes R. Botox Approved to Treat Overactive Bladder. Medscape Medical News. Jan 18 2013. [Full Text].
Myrbetriq (mirabegron) [package insert]. Northbrook, Il: Astellas Pharma. June 2012. Available at [Full Text].
Nitti VM, Herschorn S, Auerbach S, Ayers M, Lee M, Martin N. The selective (beta)3-adrenoreceptor agonist mirabegron is effective and well tolerated in patients with overactive bladder syndrome. J Urol. 2011. 185(4):e783-784.
US Food and Drug Administration. FDA Approves Botox To Treat Overactive Bladder. Jan 18 2013. [Full Text].