The Effectiveness of Anticholinergic Therapy for Overactive Bladders: Systematic Review and Meta-Analysis

Fonseca, Andrea Moura Rodrigues Maciel da; Meinberg, Mariana Furtado; Monteiro, Marilene Vale de Castro; Roque, Matheus; Haddad, Jorge Milhen; Castro, Rodrigo Aquino

doi:10.1055/s-0036-1594289

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Revista Brasileira de Ginecologia e Obstetrícia

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Review Article • Rev. Bras. Ginecol. Obstet. 38 (11) • Nov 2016 • https://doi.org/10.1055/s-0036-1594289 copy

The Effectiveness of Anticholinergic Therapy for Overactive Bladders: Systematic Review and Meta-Analysis

Eficácia da terapia anticolinérgica na bexiga hiperativa: revisão sistemática e metanálise

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The overactive bladder (OAB) has a significant negative impact on the quality of life of patients. Antimuscarinics have become the pharmacological treatment of choice for this condition. The objective of this systematic review and meta-analysis is to examine the evidence from randomized clinical trials about the outcomes of the antimuscarinic drugs available in Brazil on OABs. We searched MEDLINE and the Cochrane Central Register of Controlled Trials from the inception of these databases through to September 2015. The primary outcome measures were the mean decrease in urge urinary incontinence episodes and the mean decrease in the frequency of micturition. The results suggest that there is a moderate to high amount of evidence supporting the benefit of using anticholinergic drugs in alleviating OAB symptoms when compared with placebo. It is still not clear whether any of the specific drugs that are available in Brazil offer advantages over the others. These drugs are associated with adverse effects (dry mouth and constipation), although they are not related to an increase in the number of withdrawals.

Keywords
overactive bladder; urge incontinence; urinary frequency and antimuscarinics

	Included	Excluded
Population	Symptomatic diagnosis of overactive bladder (OAB) or a urodynamic diagnosis of detrusor over activity	OAB as consequence of surgery
Intervention	Anticholinergic drugs available in Brazil (oxybutynin 5 mg and 10 mg; darifenacin 7.5 mg and 15 mg; tolterodine 1 mg, 2 mg, and 4 mg; solifenacin 5 mg and 10 mg)	Anticholinergic drugs not available in Brazil or with different doses or routes of administration that are not available in Brazil
Comparison	Placebo, comparison between different drugs, or comparison between different doses of the same drug
Outcomes	Primary outcomes • Mean decrease in urge urinary incontinence (UUI) episodes per day • Mean decrease in the number of micturitions per daySecondary outcomes • Mean decrease in total incontinence episodes (related or not to urgency) • Dry mouth • Constipation • Withdrawals resulting from drug-related adverse effects
Study type	Randomized controlled trials (RCTs)	Non RCTs

Study	Sequence generation	Allocation concealed	Blinding	Incomplete outcome data
Appell et al.¹⁵15 Appell RA, Sand P, Dmochowski R, et al; Overactive Bladder: Judging Effective Control and Treatment Study Group. 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(4): 358-363	Unclear	Yes	Yes	Yes
Drutz et al.¹⁶16 Drutz HP, Appell RA, Gleason D, Klimberg I, Radomski S. Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 1999;10(5):283-289	Unclear	Yes	Yes	Yes
Lee et al.¹⁷17 Lee JG, Hong JY, Choo MS, et al. Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder. Int J Urol 2002;9(5):247-252	Yes	Yes	Yes	Yes
Malone-Lee et al.¹⁸18 Malone-Lee J, Shaffu B, Anand C, Powell C. Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial. J Urol 2001;165(5):1452-1456	Unclear	Unclear	Yes	Yes
Chapple et al.¹⁹19 Chapple CR, Rechberger T, Al-Shukri S, et al; YM-905 Study Group. 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(3): 303-310	Unclear	Yes	Unclear	Yes
Jacquetin et al.²⁰20 Jacquetin B, Wyndaele J. Tolterodine reduces the number of urge incontinence episodes in patients with an overactive bladder. Eur J Obstet Gynecol Reprod Biol 2001;98(1):97-102	Unclear	Yes	Unclear	Yes
Khullar et al.²¹21 Khullar V, Hill S, Laval KU, Schiøtz HA, Jonas U, Versi E. Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial. Urology 2004;64(2):269-274, discussion 274-275	Yes	Yes	Yes	Yes
Millard et al.²²22 Millard R, Tuttle J, Moore K, et al. Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity. J Urol 1999;161(5):1551-1555	Unclear	Unclear	Unclear	Yes
Swift et al.²³23 Swift S, Garely A, Dimpfl T, Payne C; Tolterodine Study Group. A new once-daily formulation of tolterodine provides superior efficacy and is well tolerated in women with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 2003;14(1):50-54, discussion 54-55	Yes	Yes	Yes	Yes
Van Kerrebroeck et al.²⁴24 Van Kerrebroeck PE, Amarenco G, Thüroff JW, et al. Dose-ranging study of tolterodine in patients with detrusor hyperreflexia. Neurourol Urodyn 1998;17(5):499-512	Unclear	Unclear	Unclear	Yes
Van Kerrebroeck et al.²⁵25 Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A; Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology 2001;57(3):414-421	Yes	Yes	Yes	Yes
Zinner et al.²⁶26 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(5):799-807	Yes	Yes	Yes	Yes
Cardozo et al.²⁷27 Cardozo L, Hessdörfer E, Milani R, et al; SUNRISE Study Group. Solifenacin in the treatment of urgency and other symptoms of overactive bladder: results from a randomized, double-blind, placebo-controlled, rising-dose trial. BJU Int 2008;102(9): 1120-1127	Unclear	Unclear	Unclear	Yes
Karram et al.²⁸28 Karram MM, Toglia MR, Serels SR, Andoh M, Fakhoury A, Forero- Schwanhaeuser S. Treatment with solifenacin increases warning time and improves symptoms of overactive bladder: results from VENUS, a randomized, double-blind, placebo-controlled trial. Urology 2009;73(1):14-18	Unclear	Unclear	Unclear	Yes
But et al.²⁹29 But I, Goldstajn MS, Oreskovic S. Comparison of two selective muscarinic receptor antagonists (solifenacin and darifenacin) in women with overactive bladder-the SOLIDAR study. Coll Antropol 2012;36(4):1347-1353	Yes	Unclear	Unclear	Yes

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[1] Address for correspondence Andrea Moura Rodrigues Maciel da Fonseca, PhD, Avenida Professor Alfredo Balena 190, 30130-100 - Belo Horizonte, Minas Gerais, Brazil (e-mail: andreamrmf@gmail.com).