Hyperactive bladder: concept of disease and paradigms in the treatment

World studies have shown that the mean prevalence of overactive bladder (OAB) ranges today from 11 to 16% of the global population and is common in both men and women. In addition, OAB is a diagnosis by exclusion. The article discusses two large groups of the causes of pathology: neurological and non-neurological. The former includes various diseases and conditions that lead to a complex abnormality in the urinary mechanism, namely, involuntary detrusor contractions and increased intravesical pressure. Spinal trauma, brain strokes and spinal strokes, multiple sclerosis, Parkinson’s disease, etc. are the most common of them. Unidentified factors constitute the second group of causes resulting in urgent frequent urination, and what is meant here is idiopathic detrusor hyperactivity (IDH). In this case, a patient may have these symptoms amidst full health without any neurological history. According to the available current guidelines, the treatment of OAB includes a three-step algorithm and suggests lifestyle changes, drug therapy and, finally, minimally invasive methods of treatment. Historically, M-anticholinergics are the main drugs for the treatment of OAD symptoms. However, administration of drugs from this group may often be impossible due to prominent side effects, which are more commonly reported among elderly patients. Unlike M-anticholinergics, Mirabegron is the only β3-adrenergic receptor agonist today that has shown a high efficacy and safety profile based on the results of large-scale placebo-controlled clinical trials.

1. 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):167–178. doi: 10.1002/nau.10052.

2. Eapen R.S., Radomski S.B. Review of the Epidemiology of Overactive Bladder. Res Rep Urol. 2016;8:71–76. doi: 10.2147/RRU.S102441.

3. Liu H.T., Chancellor M.B., Kuo H.C. Urinary Nerve Growth Factor Levels Are Elevated in Patients with Detrusor Overactivity and Decreased in Responders to Detrusor Botulinum Toxin-A Injection. Eur Urol. 2009;56(4):700–706. doi: 10.1016/j.eururo.2008.04.037.

4. Lowe E.M., Anand P., Terenghi G., Williams-Chestnut R.E., Sinicropi D.V., Osborne J.L. Increased Nerve Growth Factor Levels in the Urinary Bladder of Women with Idiopathic Sensory Urgency and Interstitial Cystitis. Br J Urol. 1997;79(4):572–577. doi: 10.1046/j.1464-410x.1997.00097.x.

5. Okragly A.J., Niles A.L., Saban R., Schmidt D., Hoffman R.L., Warner T.F. et al. Elevated Tryptase, Nerve Growth factor, Neurotrophin-3 and Glial Cell Line-Derived Neurotrophic Factor Levels in the Urine of Interstitial Cystitis and Bladder Cancer Patients. J Urol. 1999;161(2):438–441. doi: 10.1016/S0022-5347(01)61915-3.

6. Michel M.C., Chapple C.R. Basic Mechanisms of Urgency: Preclinical and Clinical Evidence. Eur Urol. 2009;56(2):298–307. doi: 10.1016/j.eururo.2009.05.028.

7. Cucchi A., Quaglini S., Rovereto B. Relationships between Micturition Urgency and Involuntary Voiding Dynamics in Men with Urinary Incontinence from Idiopathic Detrusor Overactivity. J Urol. 2007; 178(2):563–567. doi: 10.1016/j.juro.2007.03.122.

8. Cucchi A., Quaglini S., Siracusano S., Rovereto B. Urgency Degree and Bladder Contraction Velocity: Sequential Changes in Women with Idiopathic Detrusor Overactivity. Neurourol Urodyn. 2006;25(2):123–127. doi: 10.1002/nau.20217.

9. Mazo E.B., Krivoborodov G.G. Overactive Bladder. Moscow: Veche; 2003. 160 p. (In Russ.)

10. Moore E.E., Jackson S.L., Boyko E.J., Scholes D., Fihn S.D. Urinary Incontinence and Urinary Tract Infection: Temporal Relationships in Postmenopausal Women. Obstet Gynecol. 2008;111(2 Pt 1):317–323. doi: 10.1097/AOG.0b013e318160d64a.

11. Homma Y., Kakizaki H., Yamaguchi O., Yamanishi T., Nishizawa O., Yokoyama O. et al. Assessment of Overactive Bladder Symptoms: Comparison of 3-Day Bladder Diary and the Overactive Bladder Symptoms Score. Urology. 2011;77(1):60–64. doi: 10.1016/j.urology.2010.06.044.

12. Van Brummen H.J., Heintz A.P., van der Vaart C.H. The Association between Overactive Bladder Symptoms and Objective Parameters from Bladder Diary and Filling Cystometry. Neurourol Urodyn. 2004;23(1):38–42. doi: 10.1002/nau.10162.

13. Buchsbaum G.M., Albushies D.T., Guzick D.S. Utility of Urine Reagent Strip in Screening Women with Incontinence for Urinary Tract Infection. Int Urogynecol J Pelvic Floor Dysfunct. 2004;15(6):391–393. doi: 10.1007/s00192-004-1192-2.

14. Arinzon Z., Shabat S., Peisakh A., Berner Y. Clinical Presentation of Urinary Tract Infection (UTI) Differs with Aging in Women. Arch Gerontol Geriatr. 2012;55(1):145–147. doi: 10.1016/j.archger.2011.07.012.

15. Nitti V.W., Rovner E.S., Bavendam T. Response to Fesoterodine in Patients with an Overactive Bladder and Urgency Urinary Incontinence Is Independent of the Urodynamic findIng of Detrusor Overactivity. BJU Int. 2010;105(9):1268–1275. doi: 10.1111/j.1464-410X.2009.09037.x.

16. Rovner E., Kennelly M., Schulte-Baukloh H., Zhou J., Haag-Molkenteller C., Dasgupta P. Urodynamic Results and Clinical Outcomes with Intradetrusor Injections of OnabotulinumtoxinA in a Randomized, Placebo-Controlled Dose-Finding Study in Idiopathic Overactive Bladder. Neurourol Urodyn. 2011;30(4):556–562. doi: 10.1002/nau.21021.

17. Jeffcoate T.N., Francis W.J. Urgency Incontinence in the Female. Am J Obstet Gynecol. 1966;94(5):604–618. doi: 10.1016/0002-9378(66)90395-4.

18. Fantl J.A., Wyman J.F., McClish D.K., Harkins S.W., Elswick R.K., Taylor J.R., Hadley EC. Efficacy of Bladder Training in Older Women with Urinary Incontinence. JAMA. 1991;265(5):609–613. doi: 10.1001/jama.1991.03460050063021.

19. O’Donnel P.D. Biofeedback Therapy. In: Raz S. (ed.). Female Urology. 2nd ed., Philadelphia: W.B. Saunders; 1996, рр. 253–261.

20. Hay-Smith E.J., Bø K., Berghmans L.C., Hendriks H.J., de Bie R.A., van Waalwijk van Doorn E.S. WITHDRAWN: Pelvic Floor Muscle Training for Urinary Incontinence in Women. Cochrane Database Syst Rev. 2007;(1):CD001407. doi: 10.1002/14651858.CD001407.pub2.

21. Burkhard F.C., Bosch J.L.H.R., Cruz F., Lemack G.E., Nambiar A.K., Thiruchelvam N., Tubaro A. EAU Guidelines on Urinary Incontinence. Arnhem: EAU Guidelines Office; 2020. Available at: https://uroweb.org/guideline/urinary-incontinence/.

22. Shamliyan T., Wyman J., Kane R.L. Nonsurgical Treatments for Urinary Incontinence in Adult Women: Diagnosis and Comparative Effectiveness. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012. Report No.: 11(12)-EHC074-EF. Available at: https://www.ncbi.nlm.nih.gov/books/NBK92960/.

23. Sacco E., Bientinesi R. Mirabegron: A Review of Recent Data and Its Prospects in the Management of Overactive Bladder. Ther Adv Urol. 2012;4(6):315–324. doi: 10.1177/1756287212457114.

24. Dawood O., El-Zawahry A. Mirabegron. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK538513/.

25. Abrams P., Andersson K.E., Buccafusco J.J., Chapple C., de Groat W.C., Fryer A.D. et al. Muscarinic Receptors: Their Distribution and Function in Body Systems, and the Implications for Treating Overactive Bladder. Br J Pharmacol. 2006;148(5):565–578. doi: 10.1038/sj.bjp.0706780.

26. Andersson K.E. On the Site and Mechanism of Action of β3-Adrenoceptor Agonists in the Bladder. Int Neurourol J. 2017;21(1):6–11. doi: 10.5213/inj.1734850.425.

27. Igawa Y., Michel M.C. Pharmacological Profile of β3-Adrenoceptor Agonists in Clinical Development for the Treatment of Overactive Bladder Syndrome. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(3):177–183. doi: 10.1007/s00210-012-0824-1.

28. Igawa Y., Aizawa N., Homma Y. Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder. Korean J Urol. 2010;51(12):811– 818. doi: 10.4111/kju.2010.51.12.811.

29. Andersson K.E., Martin N., Nitti V. Selective β₃-Adrenoceptor Agonists for the Treatment of Overactive Bladder. J Urol. 2013;190(4):1173–1180. doi: 10.1016/j.juro.2013.02.104.

30. Andersson K.E., Arner A. Urinary Bladder Contraction and Relaxation: Physiology and Pathophysiology. Physiol Rev. 2004;84(3):935–986. doi: 10.1152/physrev.00038.2003.

31. Yamaguchi O., Marui E., Kakizaki H., Homma Y., Igawa Y., Takeda M. et al. Phase III, Randomised, Double-Blind, Placebo-Controlled Study of the β3-Adrenoceptor Agonist Mirabegron, 50 mg Once Daily, in Japanese Patients with Overactive Bladder. BJU Int. 2014;113(6):951–960. doi: 10.1111/bju.12649.

32. Ichihara K., Masumori N., Fukuta F., Tsukamoto T., Iwasawa A., Tanaka Y. A Randomized Controlled Study of the Efficacy of Tamsulosin Monotherapy and Its Combination with Mirabegron for Overactive Bladder Induced by Benign Prostatic Obstruction. J Urol. 2015;193(3): 921–926. doi: 10.1016/j.juro.2014.09.091.

33. Gratzke C., van Maanen R., Chapple C., Abrams P., Herschorn S., Robinson D. et al. Long-Term Safety and Efficacy of Mirabegron and Solifenacin in Combination Compared with Monotherapy in Patients with Overactive Bladder: A Randomised, Multicentre Phase 3 Study (SYNERGY II). Eur Urol. 2018;74(4):501–509. doi: 10.1016/j.eururo.2018.05.005.