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JOGC

No. 283-Treatments for Overactive Bladder: Focus on Pharmacotherapy

      Abstract

      Objective

      To provide guidelines for pharmacotherapy to treat overactive bladder syndrome (OAB).

      Options

      Pharmacotherapy for OAB includes anticholinergic (antimuscarinic) drugs and vaginal estrogen. Both oral and transdermal anticholinergic preparations are available.

      Outcomes

      To provide understanding of current available evidence concerning safety and clinical efficacy of pharmacotherapy for OAB; to guide selection of anticholinergic therapy based on individual patient characteristics.

      Evidence

      The Cochrane Library and Medline were searched for articles published from 1950 to the present related to individual anticholinergic drugs. Review articles on management of refractory OAB were also examined. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to 2010.

      Values

      The quality of evidence is rated and recommendations are made using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1).

      Benefits, harms, and costs

      Anticholinergics are the mainstay of pharmacotherapy for OAB. Evidence for their efficacy is mostly derived from short-term phase III randomized drug trials. Placebo response is strong, and long-term follow-up and patient subjective outcome data are lacking. Care providers need to be well acquainted with the side effects of anticholinergics and select therapy based on individual patient parameters.

      Recommendations

      • 1.
        Behavioural management protocols and functional electrical stimulation should be offered in the spectrum of effective primary treatments for overactive bladder syndrome (I-A).
      • 2.
        Oral oxybutynin, immediate and extended release, as well as transdermal oxybutynin, may be offered as treatment for overactive bladder syndrome, as they are associated with significant objective clinical improvement at 12 weeks (I-A). Oxybutynin immediate release has superior cost-effectiveness but more side effects than other anticholinergics (I-A). Adverse events associated with transdermal oxybutynin are fewer than with oral oxybutynin (I-A).
      • 3.
        Tolterodine, immediate and extended release, may be offered as treatment for overactive bladder syndrome, as it is associated with significant objective clinical improvement at 12 weeks (I-A).
      • 4.
        Trospium, immediate and extended release, may be offered as treatment for overactive bladder syndrome as it is associated with significant clinical improvement at 12 weeks (I-A). Trospium is an adequate anticholinergic choice for overactive bladder syndrome patients with pre-existing cognitive impairment (II-B) and for overactive bladder syndrome patients taking concurrent CYP450 inhibitors (III-B).
      • 5.
        Solifenacin may be offered as treatment for overactive bladder syndrome, as it is associated with significant objective clinical improvement at 12 weeks (I-A). Solifenacin may be an adequate anticholinergic choice for elderly overactive bladder syndrome patients or patients with pre-existing cognitive dysfunction (I-B).
      • 6.
        Darifenacin may be offered as treatment for overactive bladder syndrome, as it is associated with significant objective clinical improvement at 12 weeks (I-A). Darifenacin is an adequate anticholinergic choice for overactive bladder syndrome patients with pre-existing cardiac concerns or cognitive dysfunction (I-B).
      • 7
        Overactive bladder syndrome patients should be offered a choice between bladder training, functional electric stimulation, and anticholinergic therapy, as there is no difference in cure rates. Combination therapy does not have a clear advantage over one therapy alone (I-A).
      • 8
        The choice of anticholinergic therapy should be guided by individual patient comorbidities, as objective efficacy of anticholinergic drugs is similar (I-A). Dose escalation does not improve objective parameters and causes more anticholinergic adverse effects. It is, however, associated with improved subjective outcomes (I-A). To decrease side effects, switching to a lower dose or using an extended release formulation or a transdermal delivery mechanism should be considered (I-A).
      • 9
        Education on treatment efficacy, realistic expectations, and length of treatment should be offered to patients upon initiation of anticholinergic therapy, as continuation rates for anticholinergic therapy are low (III-B).
      • 10.
        Oral or transdermal estrogen supplementation should not be recommended for treatment of overactive bladder syndrome as its effects are comparable to placebo (I-E). Vaginal estrogen can be suggested for subjective improvements in overactive bladder syndrome symptoms (III-B).
      • 11.
        Intravesical botulinum toxin injection and sacral nerve and posterior tibial nerve stimulation are clinically effective options for patients with overactive bladder syndrome unresponsive to conservative options, anticholinergics, or vaginal estrogen (I-A).

      Key Words

      ABBREVIATIONS:

      CNS (central nervous system), CYP450 (cytochrome p450), ER (extended release), IR (immediate release), OAB (overactive bladder syndrome), XR (extended release)
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      References

        • Haylen B.T.
        • de Ridder D.
        • Freeman R.M.
        • et al.
        An International Urogynecological Association (IUGA)/ International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction.
        Int Urogynecol J. 2010; 21: 5-26
        • Lawrence J.M.
        • Lukacz E.S.
        • Nager C.W.
        • et al.
        Prevalence and co-occurrence of pelvic floor disorders in community-dwelling women.
        Obstet Gynecol. 2008; 111: 678-685
        • Irwin D.E.
        • 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: 1306-1315
        • Milsom I.
        • Abrams P.
        • Cardozo L.
        • et al.
        How widespread are the symptoms of overactive bladder and how are they managed? A population-based prevalence study.
        Br J Urol Int. 2001; 87: 760-766
        • Stewart W.F.
        • Van Rooyen J.B.
        • Cundiff G.W.
        • et al.
        Prevalence and burden of overactive bladder in the United States.
        World J Urol. 2003; 20: 327-336
        • Bartoli S.
        • Aguzzi G.
        • Tarricone R.
        Impact on quality of life of urinary incontinence and overactive bladder: a systematic literature review.
        Urology. 2010; 75: 491-500
        • Kelleher C.J.
        • Cardozo L.D.
        • Khullar V.
        • et al.
        A new questionnaire to assess the quality of life of urinary incontinent women.
        Br J Obstet Gynaecol. 1997; 104: 1374-1379
        • Zorn B.H.
        • Montgomery H.
        • Pieper K.
        • et al.
        Urinary incontinence and depression.
        J Urol. 1999; 162: 82-84
        • Brown J.S.
        • Vittinghoff E.
        • Wyman J.F.
        • et al.
        Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group: Collaboration.
        J Am Ger Soc. 2000; 48: 721-725
        • Thom D.H.
        • Haan M.N.
        • Van Den Eeden S.K.
        Medically recognized urinary incontinence and risks of hospitalization, nursing home admission and mortality.
        Age Ageing. 1997; 26: 367-374
        • Robert M.
        • Ross S.
        SOGC Urogynaecology Committee. Conservative management of urinary incontinence.
        J Obstet Gynaecol Can. 2006; 28: 1113-1118
        • Andersson K.E.
        • Chapple C.
        • Wein A.
        The basis for drug treatment of the overactive bladder.
        World J Urol. 2001; 19: 294-298
        • Braverman A.S.
        • Ruggieri M.R.
        • Pontari M.A.
        The M2 muscarinic receptor subtype mediates cholinergic bladder contractions in patients with neurogenic bladder dysfunction.
        J Urol. 2001; 165: 36
        • Andersson K.E.
        Antimuscarinics for treatment of overactive bladder.
        Lancet Neurol. 2004; 3: 46-53
        • Jensen D.
        Uninhibited neurogenic bladder treated with prazosin.
        Scand J Urol Nephrol. 1981; 15: 229-233
        • Tyagi S.
        • Tyagi P.
        • Van-le S.
        • et al.
        Qualitative and quantitative expression profile of muscarinic receptors in human urothelium and detrusor.
        J Urol. 2006; 176: 1673-1678
        • Giglio D.
        • Tobin G.
        Muscarinic receptor subtypes in the lower urinary tract.
        Pharmacology. 2009; 83: 259-269
        • Robinson D.
        • Cardozo L.
        New drug treatments for urinary incontinence.
        Maturitas. 2010; 65: 340-347
        • Ellsworth P.
        • Kirshenbaum E.
        Update on the pharmacologic management of overactive bladder: the present and the future.
        Urol Nurs. 2010; 30: 29-53
        • Nabi G.
        • Cody J.D.
        • Ellis G.
        • et al.
        Anticholinergic drugs versus placebo for overactive bladder syndrome in adults.
        Cochrane Database Syst Rev. 2009; (CD003781)
        • Cardozo L.
        • Thorpe A.
        • Warner J.
        • et al.
        The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.
        BJU Int. 2010; 106: 506-514
        • Cardozo L.D.
        • Cooper D.
        • Versi E.
        Oxybutynin chloride in the management of idiopathic detrusor instability.
        Neurourol Urodyn. 1987; 6: 256-257
        • Tapp A.J.
        • Cardozo L.D.
        • Versi E.
        • et al.
        The treatment of detrusor instability in post-menopausal women with oxybutynin chloride: a double- blind placebo controlled study.
        Br J Obstet Gynecol. 1990; 97: 521-526
        • Kay G.
        • Crook T.
        • Rekeda L.
        • et al.
        Differential effects of the antimuscarinic agents darifenacin and extended-release oxybutynin on recent memory in older subjects.
        Eur Urol Suppl. 2006; 5: 117
        • Katz I.R.
        • Sands L.P.
        • Bilker W.
        • et al.
        Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride.
        J Am Ger Soc. 1998; 46: 8-13
        • Wesnes K.A.
        • Edgar C.
        • Tretter R.M.
        • et al.
        Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following singe doses of solifenacin 10 mg.
        Expert Opin Drug Saf. 2009; 8: 615-626
        • Dmochowski R.R.
        • Sand P.K.
        • Zinner N.R.
        • et al.
        Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence.
        Urology. 2003; 62: 237-242
        • Staskin D.R.
        • Robinson D.
        Oxybutynin chloride topical gel: a new formulation of an established antimuscarinic therapy for overactive bladder.
        Expert Opin Pharmacother. 2009; 10: 3103-3111
        • Staskin D.R.
        • Dmochowski R.R.
        • Sand P.K.
        • 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: 1764-1772
        • Sand P.
        • Zinner N.
        • Newman D.
        • 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: 836-844
        • Kelleher C.J.
        • Reese P.R.
        • Pleil A.M.
        • et al.
        Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.
        Am J Managed Care. 2002; 8: S608-15
        • Kelleher C.J.
        • Kreder K.J.
        • Pleil A.M.
        • et al.
        Long-term health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.
        Am J Managed Care. 2002; 8: S616-30
        • Sussman D.
        • Garely A.
        Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).
        Curr Med Res Opin. 2002; 18: 177-184
        • Appell R.A.
        • 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
        • 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
        • Zinner N.
        • Gittelman M.
        • Harris R.
        • et al.
        Trospium chloride improves overactive bladder symptoms: a multi-center phase III trial.
        J Urol. 2004; 171: 2311-2315
        • Rudy D.
        • Cline K.
        • Harris R.
        • et al.
        Multicenter phase III trial studying trospium chloride in patients with overactive bladder.
        Urology. 2006; 67: 275-280
        • Sand P.K.
        • Dmochowski R.R.
        • Zinner N.R.
        • et al.
        Trospium chloride extended release is effective and well tolerated in women with overactive bladder syndrome.
        Int Urogynecol J. 2009; 20: 1431-1438
        • Dmochowski R.R.
        • Rosenberg M.T.
        • Zinner N.R.
        • et al.
        Extended-release trospium chloride improves quality of life in overactive bladder.
        Value Health. 2010; 13: 251-257
        • Biastre K.
        • Burnakis T.
        Trospium chloride treatment of overactive bladder.
        Ann Pharmacother. 2009; 43: 283-295
        • Isik A.T.
        • Celik T.
        • Bozoglu E.
        • et al.
        Trospium and cognition in patients with late onset Alzheimer disease.
        J Nutr Health Aging. 2009; 13: 672-676
        • Sandage B.
        • Sabounjian L.
        • Shipley J.
        • et al.
        Predictive power of an in vitro system to assess drug interactions of an antimuscarinic medication: a comparison of in vitro and in vivo drug- drug interaction studies of trospium chloride with digoxin.
        J Clin Pharm. 2006; 46: 776-784
        • Chapple C.R.
        • Rechberger T.
        • Al-Shukri S.
        • et al.
        Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder.
        BJU Int. 2004; 93: 303-310
        • Cardozo L.
        • Lisec M.
        • Millard R.
        • et al.
        Randomized, double-blind placebo controlled trial of the once daily muscarinic agent solifenacin succinate in patients with overactive bladder.
        J Urol. 2004; 172: 1919-1924
        • Chapple C.R.
        • Arano P.
        • Bosch J.L.
        • et al.
        Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study.
        BJU Int. 2004; 93: 71-77
        • Haab F.
        • Cardozo L.
        • Chapple C.
        • et al.
        Long-term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome.
        Eur Urol. 2005; 47: 376-384
        • Kelleher C.J.
        • Cardozo L.
        • Chapple C.R.
        • et al.
        Improved quality of life in patients with overactive bladder symptoms treated with solifenacin.
        BJU Int. 2005; 95: 81-85
        • Toglia M.R.
        • Serels S.R.
        • Laramée C.
        • et al.
        Solifenacin for overactive bladder: patient-reported outcomes from a large placebo-controlled trial.
        Postgrad Med. 2009; 121: 151-158
        • Herschorn S.
        • Stothers L.
        • Carlson K.
        • et al.
        Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: results of the VECTOR trial.
        J Urol. 2010; 183: 1892-1898
        • Wesnes K.A.
        • Edgar C.
        • Tretter R.N.
        • et al.
        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
        • 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
        • Steers W.
        • Corcos J.
        • Foote J.
        • et al.
        An investigation of dose titration with darifenacin, an M3-selective receptor antagonist.
        BJU Int. 2005; 95: 580-586
        • Hill S.
        • Khullar V.
        • Wyndaele J.J.
        • et al.
        Dose response with darifenacin, a novel once-daily M3 selective receptor antagonist for the treatment of overactive bladder: results of a fixed dose study.
        Int Urogynecol J Pelvic Floor Dysfunct. 2006; 17: 239-247
        • Chapple C.R.
        • Steers W.
        • Norton P.
        • et al.
        A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist, in the treatment of overactive bladder.
        BJU Int. 2005; 95: 993-1001
        • Chapple C.
        • DuBeau C.
        • Ebinger U.
        • et al.
        Darifenacin treatment of patients > or = 65 years with overactive bladder: results of a randomized, controlled, 12-week trial.
        Curr Med Res Opin. 2007; 23: 2347-2358
        • Olshansky B.
        • Ebinger U.
        • Brum J.
        • et al.
        Differential pharmacological effects of antimuscarinic drugs on heart rate: a randomized, placebo-controlled, double-blind, crossover study with tolterodine and darifenacin in healthy participants > or = 50 years.
        J Cardiovasc Pharmacol Ther. 2008; 13: 241-251
        • Kay G.G.
        • 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
        • Alhasso A.A.
        • McKinlay J.
        • Patrick K.
        • et al.
        Anticholinergic drugs versus non-drug active therapies for overactive bladder syndrome in adults.
        Cochrane Database Syst Rev. 2006; (CD003193)
        • Ozdedeli S.
        • Karapolat H.
        • Akkoc Y.
        Comparison of intravaginal electrical stimulation and trospium hydrochloride in women with overactive bladder syndrome: a randomized controlled study.
        Clin Rehabil. 2010; 24: 342-351
        • Chancellor M.B.
        • Kianifard F.
        • Beamer E.
        • et al.
        A comparison of the efficacy of darifenacin alone vs. darifenacin plus a behavioural modification programme upon the symptoms of overactive bladder.
        Int J Clin Pract. 2008; 62: 606-613
        • Hay-Smith J.
        • Ellis G.
        • Herbison G.P.
        Which anticholinergic drug for overactive bladder symptoms in adults.
        Cochrane Database Syst Rev. 2009; (CD005429)
        • Chapple C.R.
        • Martinez-Garcia R.
        • Selvaggi L.
        • et al.
        A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome; results of the STAR trial.
        Eur Urol. 2005; 48: 464-470
        • Zinner N.
        • Tuttle J.
        • Marks L.
        Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with overactive bladder.
        World J Urol. 2005; 23: 248-252
        • Chapple C.R.
        • Van Kerrebroeck P.E.
        • Junemann K.P.
        • et al.
        Comparison of fesoterodine and tolterodine in patients with overactive bladder.
        BJU Int. 2008; 102: 1128-1132
        • 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; 105: 58-66
        • Wilson N.M.
        • Hilmer S.N.
        • March L.M.
        • et al.
        Associations between drug burden index and falls in older people in residential aged care.
        J Am Geriatr Soc. 2011; 59: 875-880
        • D'Souza A.O.
        • Smith M.J.
        • Miller L.A.
        • et al.
        Persistence, adherence, and switch rates among extended-release and immediate- release overactive bladder medications in a regional managed care plan.
        J Manage Care Pharm. 2008; 14: 291-301
        • Salvatore S.
        • Khullar V.
        • Cardozo L.
        • et al.
        Long-term prospective randomized study comparing two different regimens of oxybutynin as a treatment for detrusor overactivity.
        Eur J Obstet Gynecol Reprod Biol. 2005; 119: 237-241
        • Yu Y.F.
        • Nichol M.B.
        • Yu A.P.
        • et al.
        Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the Californian Medicaid program.
        Value Health. 2005; 8: 495-505
        • Basra R.K.
        • Wagg A.
        • Chapple C.
        • et al.
        A review of adherence to drug therapy in patients with overactive bladder.
        BJU Int. 2008; 102: 774-779
        • DeLancey J.O.
        Anatomy.
        in: Cardozo L. Staskin D. Textbook of female urology and urogynecology. 3rd ed. Informa Healthcare, London2010
        • Cody J.D.
        • Richardson K.
        • Moehrer B.
        • et al.
        Oestrogen therapy for urinary incontinence in post-menopausal women.
        Cochrane Database Syst Rev. 2010; (CD001405)
        • Cardozo L.
        • Rekers H.
        • Tapp A.
        • et al.
        Oestriol in the treatment of postmenopausal urgency: a multicentre study.
        Maturitas. 1993; 18: 47-53
        • Rufford J.
        • Hextall A.
        • Cardozo L.
        • et al.
        A double-blind placebo- controlled trial on the effects of 25 mg estradiol implants on the urge syndrome in postmenopausal women.
        Int Urogynecol J. 2003; 14: 78-83
        • Roxburgh C.
        • Cook J.
        • Dublin N.
        Anticholinergic drugs versus other medications for overactive bladder syndrome in adults.
        Cochrane Database Syst Rev. 2007; (CD003190)
        • Leong R.K.
        • De Wachter S.G.
        • van Kerrebroeck P.E.
        Current information on sacral neuromodulation and botulinum toxin treatment for refractory idiopathic overactive bladder syndrome: a review.
        Urol Int. 2010; 84: 245-253
        • Brazzelli M.
        • Murray A.
        • Fraser C.
        Efficacy and safety of sacral nerve stimulation for urinary urge incontinence: a systematic review.
        J Urol. 2006; 175: 835-841
        • Peters K.M.
        • Carrico D.J.
        • Perez-Marrero R.A.
        • et al.
        Randomized trial of percutaneous tibial nerve stimulation versus sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial.
        J Urol. 2010; 183: 1438-1443
        • Finazzi-Agro E.
        • Petta F.
        • Sciobica F.
        • et al.
        Percutaneous tibial nerve stimulation effects on detrusor overactivity incontinence are not due to a placebo effect: a randomized, double-blind, placebo controlled trial.
        J Urol. 2010; 184: 2001-2006
        • MacDiarmid S.A.
        • Peters K.M.
        • Shobeiri S.A.
        • et al.
        Long-term durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder.
        J Urol. 2010; 183: 234-240
        • Peters K.M.
        • Macdiarmid S.A.
        • Wooldridge L.S.
        • et al.
        Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial.
        J Urol. 2009; 182: 1055-1061

      Linked Article

      • No. 353-Treatments for Overactive Bladder: Focus on Pharmacotherapy – An Addendum
        Journal of Obstetrics and Gynaecology Canada Vol. 39Issue 12
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          This technical update addendum reviews success rates and comparative evidence of the anticholinergic fesoterodine, as well as mechanism of action, safety profile, success rates, and comparative evidence of the β3 agonist mirabegron in the treatment of non-neurogenic overactive bladder syndrome (OAB). This adds to OAB pharmacotherapy recommendations initially published in 2012.
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