Pharmacotherapy for Nocturia



This chapter presents the current state of knowledge of the pharmacotherapy of nocturia. An overview of the diagnostic evaluation is followed by discussion of the indications and efficacy of different classes of medications used to treat nocturia. Nocturia, defined as voiding that occurs during the hours of sleep, is common and bothersome. The underlying causes are multiple and diverse. Determining the underlying etiology is essential for choosing the appropriate therapy. Pharmacologic treatment should be guided by a thorough clinical evaluation and data derived from a frequency-volume chart. Possible medications include those for overactive bladder (OAB), those for benign prostatic hyperplasia, and those to reduce nocturnal urine production. A systematic approach is essential for the optimal treatment of nocturia. In the absence of nocturnal polyuria, medications for BPH or overactive bladder may be employed. NP is highly prevalent among patients with nocturia, however, and antidiuretic therapy should be considered when measures to address serious underlying etiologic conditions are ineffective.


Nocturia Nocturnal polyuria Lower urinary tract pharmacotherapy Antimuscarinic therapy Overactive bladder Benign prostatic hyperplasia Antidiuretic pharmacotherapy Desmopressin 


  1. 1.
    Van Kerrebroeck P, Abrams P, Chaikin D, Donovan J, Fonda D, Jackson S, et al. Standardisation Sub-committee of the International Continence Society. The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):179–83.Google Scholar
  2. 2.
    Fitzgerald MP, Litman HJ, Link CL, McKinlay JB, Survey Investigators BACH. The association of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: results from the BACH survey. J Urol. 2007;177(4):1385–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Bosch JL, Weiss JP. The prevalence and causes of nocturia. J Urol. 2010;184(2):440–6. Review.PubMedCrossRefGoogle Scholar
  4. 4.
    Tikkinen KA, Auvinen A, Johnson TM, Weiss JP, Keränen T, Tiitinen A, et al. A systematic evaluation of factors associated with nocturia—the population-based FINNO study. Am J Epidemiol. 2009;170(3):361–8.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Kirkland JL, Lye M, Levy DW, Banerjee AK. Patterns of urine flow and electrolyte excretion in healthy elderly people. Br Med J. 1983;287(6406):1665–7.CrossRefGoogle Scholar
  6. 6.
    Hofmeester I, Kollen BJ, Steffens MG, Bosch JL, Drake MJ, Weiss JP, et al. Impact of the International Continence Society (ICS) report on the standardisation of terminology in nocturia on the quality of reports on nocturia and nocturnal polyuria: a systematic review. BJU Int. 2015;115(4):520–36.PubMedCrossRefGoogle Scholar
  7. 7.
    Blanker MH, Bohnen AM, Groeneveld FP, Bernsen RM, Prins A, Ruud Bosch JL. Normal voiding patterns and determinants of increased diurnal and nocturnal voiding frequency in elderly men. J Urol. 2000;164(4):1201–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Weiss JP. Prevalence of nocturnal polyuria in nocturia. J Urol. 2009;181((4):538.CrossRefGoogle Scholar
  9. 9.
    Asplund R, Aberg H. Diurnal variation in the levels of antidiuretic hormone in the elderly. J Intern Med. 1991;229(2):131–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Yalkut D, Lee LY, Grider J, Jorgensen M, Jackson B, Ott C. Mechanism of atrial natriuretic peptide release with increased inspiratory resistance. J Lab Clin Med. 1996;128(3):322–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Abrams P, Andersson KE. Muscarinic receptor antagonists for overactive bladder. BJU Int. 2007;100(5):987–1006.PubMedCrossRefGoogle Scholar
  12. 12.
    Andersson KE, Wein AJ. Pharmacologic management of lower urinary tract storage and emptying failure. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, editors. Campbell-Walsh urology. 11th ed. Philadelphia: Elsevier; 2016. p. 1836–74.Google Scholar
  13. 13.
    Guay DR. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clin Pharmacokinet. 2003;42(14):1243.PubMedCrossRefGoogle Scholar
  14. 14.
    Dmochowski R, Wein AJ. Lower urinary tract pharmacotherapy for nocturia. In: Weiss JP, Blaivas JG, Van Kerrebroeck P, Wein AJ, editors. Nocturia: causes, consequences and clinical approaches. New York: Springer Science+Business Media; 2012. p. 127–34.CrossRefGoogle Scholar
  15. 15.
    Brubaker L, Fitzgerald MP. Nocturnal polyuria and nocturia relief in patients treated with solifenacin for overactive bladder symptoms. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(7):737–41.PubMedCrossRefGoogle Scholar
  16. 16.
    Buser N, Ivic S, Kessler TM, Kessels AG, Bachmann LM. Efficacy and adverse events of antimuscarinics for treating overactive bladder: Network meta-analysis. Eur Urol. 2012;62(6):1040–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Toglia MR, Ostergard DR, Appell RA, Andoh M, Fakhoury A, Hussain IF. Solifenacin for overactive bladder: secondary analysis of data from VENUS based on baseline continence status. Int Urogynecol J. 2010;21(7):847–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Yokoyama O, Yamaguchi O, Kakizaki H, Itoh N, Yokota T, Ishizuka O, et al. Efficacy of solifenacin on nocturia in Japanese patients with overactive bladder: impact on sleep evaluated by bladder diary. J Urol. 2011;86(1):170–4.CrossRefGoogle Scholar
  19. 19.
    Nitti VW, Dmochowski R, Sand PK, Forst HT, Haag-Molkenteller C, Massow U, et al. J Urol. 2007;178(6):2488–94.PubMedCrossRefGoogle Scholar
  20. 20.
    Herschorn S, Swift S, Guan Z, Carlsson M, Morrow JD, Brodsky M, Gong J. BJU Int. 2010;105(1):58–66.PubMedCrossRefGoogle Scholar
  21. 21.
    Chapple C, Van Kerrebroeck P, Tubaro A, Haag-Molkenteller C, Frost HT, Massow U, et al. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder. Eur Urol. 2007;52(4):1204–12.PubMedCrossRefGoogle Scholar
  22. 22.
    Dmochowski RR, Peters KM, Morrow JD, Guan Z, Gong J, Siami P, Staskin DR. Randomized, double-blind, placebo-controlled trial of flexible-dose fesoterodine in subjects with overactive bladder. Urology. 2010;75(1):62–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Rackley R, Weiss JP, Rovner ES, Wang JT, Guan Z. Nighttime dosing with tolterodine reduces overactive bladder-related nocturnal micturitions in patients with overactive bladder and nocturia. Urology. 2006;67(4):731–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Zinner N, Gittelmen M, Harris R, Susset J, Kanelos A, Auerbach S, Trospium Study Group. Trospium chloride improves overactive bladder symptoms: a multicenter phase II trial. J Urol. 2004;171(6 Pt 1):2311–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Rudy D, Cline K, Harris R, Goldberg K, Dmochowski R. Multicenter phase III trial studying trospium chloride in patients with overactive bladder. Urology. 2006;67(2):275–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Tikkinen KA, Johnson TM, Tammela TL, Sintonen H, Haukka J, Huhtala H, Auvinen A. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010;57(3):488–96.PubMedCrossRefGoogle Scholar
  27. 27.
    Bylund DB. Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992;6(3):832–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Yoshimura K, Ohara H, Ichioka K, Terada N, Matsui Y, Terai A, Arai Y. Nocturia and benign prostatic hyperplasia. Urology. 2003;61(4):786–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Djavan B, Milani S, Davies J, Bolodeoku J. The impact of tamsulosin oral controlled absorption system (OCAS) on nocturia and the quality of sleep: preliminary results of a pilot study. Eur Urol Suppl. 2005;4(2):61–8.CrossRefGoogle Scholar
  30. 30.
    Speakman M. Efficacy and safety of tamsulosin OCAS. BJU Int. 2006;98(Suppl 2):13–7.CrossRefGoogle Scholar
  31. 31.
    Bliwise DL, Holm-Larsen T, Goble S, Norgaard JP. Short time to first void is associated with lower whole-night sleep quality in nocturia patients. J Clin Sleep Med. 2015;11(1):53–5.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Johnson TM, Jones K, Williford WO, Kutner MH, Issa MM, Lepor H. Changes in nocturia from medical treatment of benign prostatic hyperplasia: secondary analysis of the Department of Veterans Affairs Cooperative Study Trial. J Urol. 2003;170(1):145–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Johnson TM, Burrows PK, Kusek JW, Nyberg LM, Tenover JL, Lepor H, et al. The effect of doxazosin, finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia. J Urol. 2007;178(5):2045–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Roehrborn CG, Van Kerrebroeck P, Nordling J. Safety and efficacy of alfuzosin 10 mg once-daily in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. BJU Int. 2003;92(3):257–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Chapple CR, Montorsi F, Tammela TL, Wirth M, Koldewijn E, Fernandez Fernandez E, European Silodosin Study Group. Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. Eur Urol. 2011;59(3):342–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, et al. GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. J Pharmacol Exp Ther. 2007;323(1):202–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Nitti VW, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol. 2013;189(4):1388–95.PubMedCrossRefGoogle Scholar
  38. 38.
    Montecucco C, Molgó J. Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol. 2005;5(3):274–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, et al. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186–93.PubMedCrossRefGoogle Scholar
  40. 40.
    Chapple C, Sievert KD, MacDiarmid S, Khullar V, Radziszewaki 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;64(2):249–56.PubMedCrossRefGoogle Scholar
  41. 41.
    Hammer M, Vilhardt H. Peroral treatment of diabetes insipidus with a polypeptide hormone analogue, desmopressin. J Pharmacol Exp Ther. 1985;234(3):754–60.PubMedGoogle Scholar
  42. 42.
    Vilhardt H. Basic pharmacology of desmopressin. Drug Invest. 1990;2(Suppl 5):2.CrossRefGoogle Scholar
  43. 43.
    Sands JM. Molecular mechanisms of urea transport. J Membr Biol. 2003;191(3):149–63.PubMedCrossRefGoogle Scholar
  44. 44.
    Abrams P, Andersson KE, Birder L, Brubaker L, Cardozo L, Chapple C, et al. Fourth International Consultation on Incontinence Recommendations of the International Scientific Committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence. Neurourol Urodyn. 2010;29(1):213–40.PubMedCrossRefGoogle Scholar
  45. 45.
    Sakalis VI, Karavitakis M, Bedretdinova D, Bach T, Bosch JLHR, Gacci M, et al. Medical treatment of nocturia in men with lower urinary tract symptoms: systematic review by the European Association of Urology Guidelines Panel for Male Lower Urinary Tract Symptoms. Eur Urol. 2017;72(5):757–69.PubMedCrossRefGoogle Scholar
  46. 46.
    Weiss JP, Zinner NR, Klein BM, Norgaard JP. Desmopressin orally disintegrating tablet effectively reduces nocturia: results of a randomized, double-blind, placebo-controlled trial. Neurourol Urodyn. 2012;31(4):441–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Van Kerrebroeck P. Nocturia and antidiuretic therapy. In: Weiss JP, Blaivas JG, Van Kerrebroeck P, Wein AJ, editors. Nocturia: causes, consequences and clinical approaches. New York: Springer Science+Business Media; 2012. p. 135–44.CrossRefGoogle Scholar
  48. 48.
    Mattiasson A, Abrams P, Van Kerrebroeck P, Walter S, Weiss J. Efficacy of desmopressin in the treatment of nocturia: A double-blind placebo-controlled study in men. BJU Int. 2002;89(9):855–62.PubMedCrossRefGoogle Scholar
  49. 49.
    Lose G, Lalos O, Freeman RM, Van Kerrebroeck P, Nocturia Study Group. Efficacy of desmopressin (Minirin) in the treatment of nocturia: A double-blind placebo-controlled study in women. Am J Obstet Gynecol. 2003;189(4):1106–13.PubMedCrossRefGoogle Scholar
  50. 50.
    Van Kerrebroeck P, Rezapour M, Cortesse A, Thuroff J, Riis A, Norgaard JP. Desmopressin in the treatment of nocturia: A double-blind, placebo-controlled study. Eur Urol. 2007;52(1):221–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Lose G, Mattiasson A, Walter S, Lalos O, Van Kerrebroeck P, Abrams P, Freeman R. Clinical experiences with desmopressin for long-term treatment of nocturia. J Urol. 2004;172(3):1021–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Kaminetsky J, Fein S, Dmochowski R, MacDiarmid S, Abrams S, Cheng M, Wein A. Efficacy and safety of SER120 nasal spray in nocturia patients pooled analysis of 2 randomized, double-blind, placebo-controlled phase 3 trials. J Urol. 2018; Article in Press.CrossRefGoogle Scholar
  53. 53.
    Friedman FM, Weiss JP. Desmopressin in the treatment of nocturia: clinical evidence and experience. Ther Adv Urol. 2013;5(6):310–7.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Smith Institute for UrologyGreenlawnUSA
  2. 2.Department of UrologySUNY Downstate Medical CenterBrooklynUSA

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