Neuro-Urology pp 365-383 | Cite as

Pharmacologic Management of Neurogenic Lower Urinary Tract Dysfunction

  • Casey G. Kowalik
  • Sophia Delpe
  • Roger DmochowskiEmail author


Lower urinary tract function requires complex and coordinated signaling between central and peripheral nervous systems. In patients with neurologic lesions, the development of neurogenic lower urinary tract dysfunction (NLUTD) can include neurogenic detrusor overactivity (NDO), detrusor areflexia, detrusor sphincter dyssynergia (DSD), or sphincter underactivity depending on the locations and extent of the lesion. The pharmacologic management of NLUTD is reviewed in this chapter following a brief summary of neurologic control of micturition and assessment of NLUTD. Antimuscarinics with or without intermittent catheterization are the first-line management of NDO, but mirabegron is a newer agent that has also shown efficacy in this population. Botulinum toxin A (BTX-A) injections into the detrusor muscle can be considered if medical therapy fails. Medical therapy for DSD has not been demonstrated as efficacious, but intrasphincteric BTX-A can be considered as an alternative to sphincterotomy. No medical therapy has been shown effective for the management of detrusor areflexia or sphincter underactivity. Lifelong follow-up is necessary to prevent the development of secondary complications, such as renal failure.


Neurogenic bladder Detrusor sphincter dyssynergia Antimuscarinics Beta agonists Botulinum toxin A 


  1. 1.
    Mansfield KJ, Liu L, Mitchelson FJ, et al. Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing. Br J Pharmacol. 2005;144:1089–99.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    de Groat WC, Griffiths D, Yoshimura N. Neural control of the lower urinary tract. Compr Physiol. 2015;5:327–96.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Andersson K-E, Arner A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev. 2004;84:935–86. Scholar
  4. 4.
    Yoshimura N, Chancellor MB. Neurophysiology of lower urinary tract function and dysfunction. Rev Urol. 2003;5:S3–S10.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9:453–66. Scholar
  6. 6.
    Thor KB, Donatucci C. Central nervous system control of the lower urinary tract: new pharmacological approaches to stress urinary incontinence in women. J Urol. 2004;172:27–33. Scholar
  7. 7.
    McCloskey KD. Interstitial cells of cajal in the urinary tract. In: Andersson K-E, Michel MC, editors. Urinary tract. Berlin: Springer; 2011. p. 233–54.CrossRefGoogle Scholar
  8. 8.
    Juszczak K, Maciukiewicz P, Drewa T, Thor P. Cajal–like interstitial cells as a novel target in detrusor overactivity treatment: true or myth? Cent Eur J Urol. 2013;66:1–5. Scholar
  9. 9.
    Chai TC, Birder LA. Physiology and pharmacology of the bladder and urethra. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, editors. Campbell-Walsh urology, 11th ed. 2016. p. 1631–84.Google Scholar
  10. 10.
    Pakzad M, Ikeda Y, McCarthy C, et al. Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders. Naunyn Schmiedeberg’s Arch Pharmacol. 2016;389:921–9. Scholar
  11. 11.
    Jean-Xavier C, Sharples SA, Mayr KA, et al. Retracing your footsteps: developmental insights to spinal network plasticity following injury. J Neurophysiol. 2017.
  12. 12.
    McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol. 1981;126:205–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Weld KJ, Graney MJ, Dmochowski RR. Difference in bladder compliance with time and associations of bladder management with compliance in spinal cord injured patients. J Urol. 2000;163:1228–33.CrossRefPubMedGoogle Scholar
  14. 14.
    Tarcan T, Sekerci CA, Akbal C, et al. Is 40 cm H2O detrusor leak point pressure cut-off reliable for upper urinary tract protection in children with myelodysplasia? Neurourol Urodyn. 2016;36:759–63. Scholar
  15. 15.
    Weld KJ, Graney MJ, Dmochowski RR. Clinical significance of detrusor sphincter dyssynergic type in patients with post-traumatic spinal cord injury. Urology. 2000;56:565–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Abrams P, Cardozo L, Fall M, 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;21:167–78. Scholar
  17. 17.
    Wein AJ. Classification of neurogenic voiding dysfunction. J Urol. 2081;125:605–9.CrossRefGoogle Scholar
  18. 18.
    Agrawal S, Agrawal RR, Wood HM. Establishing a multidisciplinary approach to the management of neurologic disease affecting the urinary tract. Urol Clin North Am. 2017;44:377–89. Scholar
  19. 19.
    Feneley RCL, Hopley IB, Wells PNT. Urinary catheters: history, current status, adverse events and research agenda. J Med Eng Technol. 2015;39:459–70. Scholar
  20. 20.
    Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J Urol. 1972;107:458–61.CrossRefPubMedGoogle Scholar
  21. 21.
    Chen TYH, Ponsot Y, Carmel M, et al. Multi-Centre study of Intraurethral valve-pump catheter in women with a hypocontractile or acontractile bladder. Eur Urol. 2005;48:628–33. Scholar
  22. 22.
    Finkbeiner AE. Is bethanechol chloride clinically effective in promoting bladder emptying? A literature review. J Urol. 1985;134:443–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Riedl CR, Stephen RL, Daha LK, et al. Electromotive administration of intravesical bethanechol and the clinical impact on acontractile detrusor management: introduction of a new test. J Urol. 2000;164:2108–11.CrossRefPubMedGoogle Scholar
  24. 24.
    Hindley RG, Brierly RD, Thomas PJ. Prostaglandin E2 and bethanechol in combination for treating detrusor underactivity. BJU Int. 2004;93(1):89–92. Scholar
  25. 25.
    Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M. Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis. Eur Urol. 2012;62:816–30. Scholar
  26. 26.
    Madersbacher H, Murtz G, Stohrer M. Neurogenic detrusor overactivity in adults: a review on efficacy, tolerability and safety of oral antimuscarinics. Spinal Cord. 2013;51:432–41. Scholar
  27. 27.
    Andersson K-E, Wein AJ. Pharmacologic management of lower urinary tract storage and emptying failure. In: Campbell-Walsh urology. 11th ed. Philadelphia: Elsevier; 2016. p. 1836–1874.e23.Google Scholar
  28. 28.
    Davila GW, Daugherty CA, Sanders SW. A short-term, multicenter, randomized double-blind dose titration study of efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol. 2001;166:140–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Kennelly MJ, Lemack GE, Foote JE, Trop CS. Efficacy and safety of oxybutynin transdermal system in spinal cord injury patients with neurogenic detrusor overactivity and incontinence: an open-label, dose-titration study. Urology. 2009;74:741–5. Scholar
  30. 30.
    Krause P, Fuhr U, Schnitker J, et al. Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study. J Urol. 2013;190:1791–7. Scholar
  31. 31.
    Schröder A, Albrecht U, Schnitker J, et al. Efficacy, safety, and tolerability of intravesically administered 0.1% oxybutynin hydrochloride solution in adult patients with neurogenic bladder: a randomized, prospective, controlled multi-center trial. Neurourol Urodyn. 2015;35:582–8. Scholar
  32. 32.
    De Wachter S, Wyndaele J. Intravesical oxybutynin: a local anesthetic effect on bladder C afferents. J Urol. 2003;169:1892–5. Scholar
  33. 33.
    van Kerrebroeck PEVA, Amarenco G, Thuroff JW, et al. Dose-ranging study of tolterodine in patients with detrusor hyperreflexia. Neurourol Urodyn. 1998;17:499–512.CrossRefPubMedGoogle Scholar
  34. 34.
    Ethans KD, Nance PW, Bard RJ, et al. Efficacy and safety of tolterodine in people with neurogenic detrusor overactivity. J Spinal Cord Med. 2004;27:214–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Watanabe M, Yamanishi T, Honda M, et al. Efficacy of extended-release tolterodine for the treatment of neurogenic detrusor overactivity and/or low-compliance bladder. Int J Urol. 2010;17:931–6. Scholar
  36. 36.
    Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith J. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev. 2012;1:CD005429. Scholar
  37. 37.
    Nilvebrant L, Andersson KE, Gilberg PG, et al. Tolterodine—a new bladder-selective antimuscarinic agent. Eur J Pharmacol. 1997;327:195–207.CrossRefPubMedGoogle Scholar
  38. 38.
    Bycroft J, Leaker B, Wood S, et al. The effect of darifenacin on neurogenic detrusor overactivity in patients with spinal cord injury. International Continence Society. 2003.Google Scholar
  39. 39.
    Carl S, Laschke S. Darifenacin is also effective in neurogenic bladder dysfunction (multiple sclerosis). Urology. 2006;68(Suppl):250–1. Scholar
  40. 40.
    Amarenco G, Sutory M, Zachoval R, et al. Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study. Neurourol Urodyn. 2017;36(2):414–21. Scholar
  41. 41.
    Stohrer M, Bauer P, Giannetii BM, et al. Effect of trospium chloride on urodynamic parameters in patients with detrusor hyperreflexia due to spinal cord injuries. Urol Int. 1991;47:138–43.CrossRefPubMedGoogle Scholar
  42. 42.
    Madersbacher H, Stohrer M, Richter R, et al. Trospium chloride versus oxybutynin: a randomized, double- blind, multicentre trial in the treatment of detrusor hyper- reflexia. Br J Urol. 1995;75:452–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Menarini M, Del Popolo G, Di Benedetto P, et al. Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to patients? Int J Clin Pharmacol Ther. 2006;44:623–32.CrossRefPubMedGoogle Scholar
  44. 44.
    Stohrer M, Madersbacher H, Richter R, et al. Efficacy and safety of propiverine in SCI-patients suffering from detrusor hyperreflexia—a double-blind, placebo-controlled clinical trial. Spinal Cord. 1999;37(3):196–200.CrossRefPubMedGoogle Scholar
  45. 45.
    Stohrer M, Murtz G, Kramer G, et al. Efficacy and tolerability of propiverine hydrochloride extended-release compared with immediate-release in patients with neurogenic detrusor overactivity. Spinal Cord. 2013;51:419–23. Scholar
  46. 46.
    Stöhrer M, Mürtz G, Kramer G, et al. Propiverine compared to oxybutynin in neurogenic detrusor overactivity—results of a randomized, double-blind, multicenter clinical study. Eur Urol. 2007;51:235–42. Scholar
  47. 47.
    Wollner J, Pannek J. Initial experience with the treatment of neurogenic detrusor overactivity with a new beta-3 agonist (mirabegron) in patients with spinal cord injury. Spinal Cord. 2016;54:78–82. Scholar
  48. 48.
    Wada N, Shimizu T, Takai S, et al. Combinational effects of muscarinic receptor inhibition and β3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury. Neurourol Urodyn. 2016;36:1039–45. Scholar
  49. 49.
    Nitti VW, Auerbach S, Martin N, et al. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol. 2013;189:1388–95. Scholar
  50. 50.
    Nitti VW, Rosenberg S, Mitcheson DH, et al. Urodynamics and safety of the β3-Adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. J Urol. 2013;190:1320–7.
  51. 51.
    Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns? Curr Pharm Des. 2004;10:2463–75.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Amend B, Hennenlotter J, Schäfer T, et al. Effective treatment of neurogenic detrusor dysfunction by combined high-dosed antimuscarinics without increased side-effects. Eur Urol. 2008;53:1021–8. Scholar
  53. 53.
    Cameron AP, Clemens JQ, Latini JM, McGuire EJ. Combination drug therapy improves compliance of the neurogenic bladder. J Urol. 2009;182:1062–7. Scholar
  54. 54.
    Tanaka I, Nagase K, Tanase K, et al. Improvement in neurogenic detrusor overactivity by peripheral C fiber’s suppression with cyclooxygenase inhibitors. J Urol. 2010;183:786–92. Scholar
  55. 55.
    Kumar A, Prabha R, Paul T, et al. Tramadol inhibits the contractility of isolated caprine detrusor muscle. Auton Autacoid Pharmacol. 2012;32:15–22. Scholar
  56. 56.
    Schurch B, Stohrer M, Kramer G, et al. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164:692–7.CrossRefPubMedGoogle Scholar
  57. 57.
    Rovner E, Kohan A, Chartier-Kastler E, et al. Long-term efficacy and safety of onabotulinumtoxinA in patients with neurogenic detrusor overactivity who completed 4 years of treatment. J Urol. 2016;196:801–8. Scholar
  58. 58.
    Pannek J, Blok B, Castro-Diaz D, et al. Guidelines on neurogenic lower urinary tract dysfunction. Eur Urol. 2009;56(1):81–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Agrawal M, Joshi M. Urodynamic patterns after traumatic spinal cord injury. J Spinal Cord Med. 2015;38:128–33.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Blaivas JG, Sinha HP, Zayed AAH, Labib KB. Detrusor-external sphincter dyssynergia. J Urol. 1981;125:542–4.CrossRefPubMedGoogle Scholar
  61. 61.
    Stoffel JT. Detrusor sphincter dyssynergia: a review of physiology, diagnosis, and treatment strategies. Trans Androl Urol. 2016;5:127–35.CrossRefGoogle Scholar
  62. 62.
    Bushman W, Steers WD, Meythaler JM. Voiding dysfunction in patients with spastic paraplegia: urodynamic evaluation and response to continuous intrathecal baclofen. Neurourol Urodyn. 1993;12:163–70.CrossRefPubMedGoogle Scholar
  63. 63.
    Hackler RH, Broecker BH, Klein FA, Brady SM. A clinical experience with dantrolene sodium for external urinary sphincter hypertonicity in spinal cord injured patients. J Urol. 1980;124:78–80.CrossRefPubMedGoogle Scholar
  64. 64.
    Chancellor MB, Erhard MJ, Rivas DA. Clinical effect of alpha-1 antagonism by terazosin on external and internal urinary sphincter function. J Am Paraplegia Soc. 1993;16:207–14.CrossRefPubMedGoogle Scholar
  65. 65.
    Dykstra DD, Sidi AA, Scott AB, et al. Effects of botulinum a toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol. 1988;139:919–22.CrossRefPubMedGoogle Scholar
  66. 66.
    Chen S, Bih L, Huang Y, et al. Effect of single botulinum toxin A injection to the external urethral sphincter for treating detrusor external sphincter dyssynergia in spinal cord injury. J Rehabil Med. 2008;40:744–8. Scholar
  67. 67.
    Utomo E, Groen J, Blok BF. Surgical management of functional bladder outlet obstruction in adults with neurogenic bladder dysfunction. Cochrane Database Syst Rev. 2014;(5):CD004927.
  68. 68.
    Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with Botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990;71(1):24–6.PubMedGoogle Scholar
  69. 69.
    Phelan MW, Franks M, Somogyi GT, et al. Botulinum toxin urethral sphincter injection to restore bladder emptying in men and women with voiding dysfunction. J Urol. 2001;165:1107–10.CrossRefPubMedGoogle Scholar
  70. 70.
    Mariappan P, Alhasso A, Ballantyne Z, et al. Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI) for the treatment of stress urinary incontinence: a systematic review. Eur Urol. 2007;51:67–74. Scholar
  71. 71.
    Wilson JLL, Miranda CA, Knepper MA. Vasopressin and the regulation of aquaporin-2. Clin Exp Nephrol. 2013;17:751–64. Scholar
  72. 72.
    Bosma R, Wynia K, Havlikova E, et al. Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis. Acta Neurol Scand. 2005;112:1–5. Scholar
  73. 73.
    Goh MY, Millard MS, Wong ECK, et al. Diurnal blood pressure and urine production in acute spinal cord injury compared with controls. Spinal Cord. 2017;55:39–46. Scholar
  74. 74.
    Szollar SM, Dunn KL, Brandt S, Fincher J. Nocturnal polyuria and antidiuretic hormone levels in spinal cord injury. Arch Phys Med Rehabil. 1997;78:455–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Eldahan KC, Rabchevsky AG. Autonomic dysreflexia after spinal cord injury: systemic pathophysiology and methods of management. Auton Neurosci. 2017;209:1–12. Scholar
  76. 76.
    Chancellor MB, Erhard MJ, Hirsch IH, Stass WE Jr. Prospective evaluation of terazosin for the treatment of autonomic dysreflexia. J Urol. 1994;151:111–3.CrossRefPubMedGoogle Scholar
  77. 77.
    Chan YY, Sandlin SK, Kurzrock EA, Osborn SL. The current use of stem cells in bladder tissue regeneration and bioengineering. Biomedicine. 2017;5:4. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Casey G. Kowalik
    • 1
  • Sophia Delpe
    • 1
  • Roger Dmochowski
    • 1
    Email author
  1. 1.Department of Urologic SurgeryVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations