Drug Safety

, Volume 33, Issue 4, pp 261–271 | Cite as

Is There Still a Role for Desmopressin in Children with Primary Monosymptomatic Nocturnal Enuresis?

A Focus on Safety Issues
  • Johan Van de Walle
  • Charlotte Van Herzeele
  • Ann Raes
Current Opinion


It has recently became apparent that severe primary monosymptomatic nocturnal enuresis (MNE) has a worse prognosis than generally believed, and may have major consequences on the well-being of the child, thus making treatment mandatory. Desmopressin is one of the most widely prescribed medications for MNE, and in this current opinion article we discuss the safety of desmopressin in children with this condition.

Following a US FDA request in December 2007 that the prescribing information for desmopressin nasal spray be updated, desmopressin spray is no longer indicated for the treatment of MNE or for use in patients at risk for hyponatraemia.

Multiple reports of hyponatraemia in patients with nocturia (mainly the elderly) led to an increased awareness of the risks associated with desmopressin. While the pathogenesis of hyponatraemia in those over 65 years of age relates more to changing renal water and solute handling, we believe that in the young, overdosing and insufficient fluid restriction are usually the major causes.

Hyponatraemia is most frequently reported when desmopressin is administered by nasal spray compared with the tablet formulation. This may simply reflect the fact that for more than 10 years the spray was the only available mode of administration in many countries. However, it may also reflect the higher biodisponibility and/or intraindividual variability of pharmacokinetics of the spray compared with the tablet. There are few serious adverse events reported for the melt formulation (oral lyophilisate), but as it has only recently become available on the market, it would be premature to conclude that it has a better safety profile.

We believe that desmopressin in all formulations has a good safety profile in children with MNE, provided that treatment is properly prescribed and monitored; improving the training of doctors and patients in the dose-response kinetics of the drug, teaching appropriate restriction of fluid intake and by encouraging the use of desmopressin within a narrow dose range (10–20 μg spray, 120–240 μg melt and 200–400 μg tablet) when used in primary-care settings. Titrating higher doses in therapy-resistant patients should probably be carried out in a specialized enuresis centre, and only after documenting adequate morning urinary diluting capacity.

In summary, the risk of hyponatraemia is exacerbated by misuse of the drug rather than an inherent danger associated with the drug, which in our opinion should be addressed with better education rather than withdrawal of a medication that has the potential to benefit children with nocturnal enuresis.


Desmopressin Nocturnal Enuresis Nocturnal Polyuria Antidiuretic Effect Monosymptomatic Nocturnal Enuresis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this current opinion article. J. Van de Walle is a member of the Safety Advisory Board of Ferring Pharmaceuticals. J. Van de Walle and C. Van Herzeele are investigators on the ongoing DRIP (A Study of Oral Desmopressin in Previously Untreated Children Aged 5 to 15 Years With Primary Nocturnal Enuresis) study, which is funded by Ferring Pharmaceuticals, and C. Van Herzeele is funded by a grant from Ferring Pharmaceuticals. Ann Raes has no conflicts of interest to declare that are relevant to the content of this current opinion article.


  1. 1.
    Hjalmas K, Arnold T, Bower W, et al. Nocturnal enuresis: an international evidence based management strategy. J Urol 2004 Jun; 171 (6 Pt 2): 2545–61PubMedCrossRefGoogle Scholar
  2. 2.
    Yeung CK, Sreedhar B, Sihoe JD, et al. Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU Int 2006 May; 97(5): 1069–73PubMedCrossRefGoogle Scholar
  3. 3.
    Hinde M, Hjertonsson M, Broberg A. Low self esteem of children with enuresis: mental and social health compared in different groups. Lakartidningen 1995 Sep 6; 92(36): 3225–9PubMedGoogle Scholar
  4. 4.
    Joinson C, Heron J, Butler U, et al. Psychological differences between children with and without soiling problems. Pediatrics 2006 May; 117(5): 1575–84PubMedCrossRefGoogle Scholar
  5. 5.
    Hagglof B, Andren O, Bergstrom E, et al. Self-esteem before and after treatment in children with nocturnal enuresis and urinary incontinence. Scand J Urol Nephrol Suppl 1997; 183: 79–82PubMedGoogle Scholar
  6. 6.
    Wagner WG, Smith D, Norris WR. The psychological adjustment of enuretic children: acomparison of two types. J Pediatr Psychol 1988 Mar; 13(1): 33–8PubMedCrossRefGoogle Scholar
  7. 7.
    Hagglof B, Andren O, Bergstrom E, et al. Self-esteem in children with nocturnal enuresis and urinary incontinence: improvement of self-esteem after treatment. Eur Urol 1998; 33 Suppl. 3: 16–9PubMedCrossRefGoogle Scholar
  8. 8.
    Theunis M, Van Hoecke E, Paesbrugge S, et al. Self-image and performance in children with nocturnal enuresis. Eur Urol 2002 Jun; 41(6): 660–7, discussion 667PubMedCrossRefGoogle Scholar
  9. 9.
    Butler R, McKenna S. Overcoming parental intolerance in childhood nocturnal enuresis: a survey of professional opinion. BJU Int 2002 Feb; 89(3): 295–7PubMedCrossRefGoogle Scholar
  10. 10.
    Yeung CK, Diao M, Sreedhar B. Cortical arousal in children with severe enuresis. N Engl J Med 2008 May 29; 358(22): 2414–5PubMedCrossRefGoogle Scholar
  11. 11.
    Yuen-Keng Ng, His-Yang Wu, Kim Hung Lee, et al. Bladder reduction surgery accelerates the appearance of spontaneous voiding in neonatal rats. J Urol 2010; 183: 370–7CrossRefGoogle Scholar
  12. 12.
    Yeung CK. Bladder dysfunction, sleep arousal disturbance and impairment of CNS function in enuretic children. International Children’s Continence Society (ICCS) Course and International Enuresis Symposium; 2007 Nov 30–Dec 2; Hong KongGoogle Scholar
  13. 13.
    Dhondt K, Raes A, Hoebeke P, et al. Abnormal sleep architecture and refractory nocturnal enuresis. J Urol 2009 Oct; 182 (4 Suppl.): 1961–5PubMedCrossRefGoogle Scholar
  14. 14.
    Baeyens D, Roeyers H, Naert S, et al. The impact of maturation of brainstem inhibition on enuresis: a startle eye blink modification study with 2-year followup. J Urol 2007 Dec; 178(6): 2621–5PubMedCrossRefGoogle Scholar
  15. 15.
    Järvelin MR, Moilanen I, Vikeväinen-Tervonen L, et al. Life changes and protective capacities in enuretic and non-enuretic children. J Child Psychol Psychiatry 1990; 31: 763–74PubMedCrossRefGoogle Scholar
  16. 16.
    Rey JM, Hensley VR. Bedwetting and psychopathology in adolescents. J Paediatr Child Health 1995; 31: 508–12PubMedCrossRefGoogle Scholar
  17. 17.
    Von Gontard A, Lehmkuhl G. Enuresis nocturna: neue Ergebnisse zu genetischen, pathophysiologischen und psychiatrischen Zusammenhängen. Prax Kinderpsychychol Kinderpsychiatr 1997; 46: 709–26Google Scholar
  18. 18.
    Klackenberg G. Nocturnal enuresis in a longitudinal perspective. Acta Paediatr Scand 1981; 70: 453–7PubMedCrossRefGoogle Scholar
  19. 19.
    Byrd RS, Weitzman M, Lanphear NE, et al. Bedwetting in US children: epidemiology and related behaviour problems. Pediatrics 1996; 98: 414–9PubMedGoogle Scholar
  20. 20.
    Fergusson DM, Horwood LJ. Nocturnal enuresis and behavioural problems in adolescence: a 15-year longitudinal study. Pediatrics 1994; 94: 662–7PubMedGoogle Scholar
  21. 21.
    Nijman R, Bower W, Ellsworth P, et al. Diagnosis and management of urinary incontinence and encopresis in childhood. In: Abrams P, Cardozo L, Khoury S, et al., 270 editors. Incontinence. 3rd ed. Plymouth: Health Publications Ltd, 2005: 965–1058Google Scholar
  22. 22.
    Neveus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006 Jul; 176(1): 314–24PubMedCrossRefGoogle Scholar
  23. 23.
    Baeyens D, Roeyers H, Van Erdeghem S, et al. The prevalence of attention deficit-hyperactivity disorder in children with nonmonosymptomatic nocturnal enuresis: a 4-year followup study. J Urol 2007 Dec; 178(6): 2616–20PubMedCrossRefGoogle Scholar
  24. 24.
    Baeyens D, Roeyers H, Demeyere I, et al. Attention-deficit/hyperactivity disorder (ADHD) as a risk factor for persistent nocturnal enuresis in children: a two-year follow-up study. Acta Paediatrica 2005; 94: 1619–25PubMedCrossRefGoogle Scholar
  25. 25.
    Crimmins CR, Rathbun SR, Husmann DA. Management of urinary incontinence and nocturnal enuresis in attention-deficit hyperactivity disorder. J Urol 2003 Oct; 170 (4 Pt 1): 1347–50PubMedCrossRefGoogle Scholar
  26. 26.
    Baeyens D, Roeyers H, Hoebeke P, et al. The impact of attention deficit hyperactivity disorders on brainstem dysfunction in nocturnal enuresis. J Urol 2006 Aug; 176(2): 744–8PubMedCrossRefGoogle Scholar
  27. 27.
    Ornitz EM, Russell AT, Hanna GL, et al. Prepulse inhibition of startle and the neurobiology of primary nocturnal enuresis. Biol Psychiatry 1999; 45: 1455–66PubMedCrossRefGoogle Scholar
  28. 28.
    Mahler B, Kamperis K, Schroeder M, et al. Sleep deprivation induces diuresis and natriuresis in healthy children. Aarhus: The Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University, 2009Google Scholar
  29. 29.
    Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children’s Continence Society. J Urol 2010; 183: 441–7PubMedCrossRefGoogle Scholar
  30. 30.
    Lackgren G, Lilja B, Neveus T, et al. Desmopressin in the treatment of severe nocturnal enuresis in adolescents: a 7-year follow-up study. Br J Urol 1998 May; 81 Suppl. 3: 17–23PubMedCrossRefGoogle Scholar
  31. 31.
    Hjalmas K. SWEET, the Swedish Enuresis Trial. Scand J Urol Nephrol Suppl 1995; 173: 89–92, discussion 93PubMedGoogle Scholar
  32. 32.
    Norgaard JP, Rittig S, Djurhuus JC. Nocturnal enuresis: an approach to treatment based on pathogenesis. J Pediatr 1989 Apr; 114 (4 Pt 2): 705–10PubMedCrossRefGoogle Scholar
  33. 33.
    Robson WL, Leung AK, Norgaard JP. The comparative safety of oral versus intranasal desmopressin for the treatment of children with nocturnal enuresis. J Urol 2007 Jul; 178(1): 24–30PubMedCrossRefGoogle Scholar
  34. 34.
    Lottmann H, Froeling F, Alloussi S, et al. A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresis. Int J Clin Pract 2007 Sep; 61(9): 1454–60PubMedCrossRefGoogle Scholar
  35. 35.
    Butler RJ, Holland P, Gasson S, et al. Exploring potential mechanisms in alarm treatment for primary nocturnal enuresis. Scand J Urol Nephrol 2007; 41(5): 407–13PubMedCrossRefGoogle Scholar
  36. 36.
    Oredsson AF, Jorgensen TM. Changes in nocturnal bladder capacity during treatment with the bell and pad for monosymptomatic nocturnal enuresis. J Urol 1998 Jul; 160(1): 166–9PubMedCrossRefGoogle Scholar
  37. 37.
    Muller D, Roehr CC, Eggert P. Comparative tolerability of drug treatment for nocturnal enuresis in children. Drug Saf 2004; 27(10): 717–27PubMedCrossRefGoogle Scholar
  38. 38.
    Glazener CM, Evans JH. Desmopressin for nocturnal enuresis in children. Cochrane Database Syst Rev 2002; (3): CD002112Google Scholar
  39. 39.
    Van Hoeck K, Bael A, Lax H, et al. Urine output rate and maximum volume voided in school-age children with and without nocturnal enuresis. J Pediatr 2007 Dec; 151(6): 575–80PubMedCrossRefGoogle Scholar
  40. 40.
    Lottmann H, Baydala L, Eggert P, et al. Long-term desmopressin response in primary nocturnal enuresis: open-label, multinational study. Int J Clin Pract 2009 Jan; 63(1): 35–45PubMedCrossRefGoogle Scholar
  41. 41.
    Schulz-Juergensen S, Rieger M, Schaefer J, et al. Effect of 1-desamino-8-D-arginine vasopressin on prepulse inhibition of startle supports a central etiology of primary monosymptomatic enuresis. J Pediatr 2007 Dec; 151(6): 571–4PubMedCrossRefGoogle Scholar
  42. 42.
    Van de Walle J, Stockner M, Raes A, et al. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf 2007 Sep; 2(3): 232–8CrossRefGoogle Scholar
  43. 43.
    Jacquin P, Ouvry O, Alvin P. Fatal water intoxication in a young patient with anorexia nervosa. J Adolesc Health 1992 Nov; 13(7): 631–3PubMedCrossRefGoogle Scholar
  44. 44.
    Dehoorne JL, Raes AM, van Laecke E, et al. Desmopressin toxicity due to prolonged half-life in 18 patients with nocturnal enuresis. J Urol 2006 Aug; 176(2): 754–8PubMedCrossRefGoogle Scholar
  45. 45.
    A/S FP. Data on file, Ferring Pharmaceuticals, 2005Google Scholar
  46. 46.
    De Guchtenaere A, Raes A, Van de Walle C, et al. Evidence of partial anti-enuretic response related to poor pharmacodynamic effects of desmopressin nasal spray. J Urol 2009 Jan; 181(1): 302–9, discussion 309PubMedCrossRefGoogle Scholar
  47. 47.
    Fjellestad-Paulsen A, Hoglund P, Lundin S, et al. Pharmacokinetics of 1-deamino-8-D-arginine vasopressin after various routes of administration in healthy volunteers. Clin Endocrinol (Oxf) 1993 Feb; 38(2): 177–82CrossRefGoogle Scholar
  48. 48.
    Van de Walle JG, Bogaert GA, Mattsson S, et al. A new fast-melting oral formulation of desmopressin: a pharmacodynamic study in children with primary nocturnal enuresis. BJU Int 2006 Mar; 97(3): 603–9CrossRefGoogle Scholar
  49. 49.
    Rittig S, Jensen AR, Jensen KT, et al. Effect of food intake on the pharmacokinetics and antidiuretic activity of oral desmopressin (DDAVP) in hydrated normal subjects. Clin Endocrinol (Oxf) 1998 Feb; 48(2): 235–41CrossRefGoogle Scholar
  50. 50.
    Richardson DW, Robinson AG. Desmopressin. Ann Intern Med 1985 Aug; 103(2): 228–39PubMedGoogle Scholar
  51. 51.
    Rembratt A, Graugaard-Jensen C, Senderovitz T, et al. Pharmacokinetics and pharmacodynamics of desmopressin administered orally versus intravenously at daytime versus night-time in healthy men aged 55–70 years. Eur J Clin Pharmacol 2004 Aug; 60(6): 397–402PubMedCrossRefGoogle Scholar
  52. 52.
    Osterberg O, Savic RM, Karlsson MO, et al. Pharmacokinetics of desmopressin administrated as an oral lyophilisate dosage form in children with primary nocturnal enuresis and healthy adults. J Clin Pharmacol 2006 Oct; 46(10): 1204–11PubMedCrossRefGoogle Scholar
  53. 53.
    Rembratt A, Norgaard JP, Andersson KE. Desmopressin in elderly patients with nocturia: short-term safety and effects 271 on urine output, sleep and voiding patterns. BJU Int 2003 May; 91(7): 642–6PubMedCrossRefGoogle Scholar
  54. 54.
    Rembratt A, Riis A, Norgaard JP. Desmopressin treatment in nocturia; an analysis of risk factors for hyponatremia. Neurourol Urodyn 2006; 25(2): 105–9PubMedCrossRefGoogle Scholar
  55. 55.
    Miller M. Fluid and electrolyte homeostasis in the elderly: physiological changes of ageing and clinical consequences. Baillieres Clin Endocrinol Metab 1997 Jul; 11(2): 367–87PubMedCrossRefGoogle Scholar
  56. 56.
    Van Herzeele C, Alova I, Evans J, et al. Poor compliance with primary nocturnal enuresis therapy may contribute to insufficient desmopressin response. J Urol 2009 Oct; 182 (4 Suppl.): 2045–9PubMedCrossRefGoogle Scholar
  57. 57.
    Rittig S, Jensen AR, Jensen KT, et al. Desmopressin tablet treatment: factors influencing gastrointestinal absorption. Scand J Urol Nephrol Suppl 1997; 183: 51–2PubMedGoogle Scholar
  58. 58.
    Matthiesen TB, Rittig S, Djurhuus JC, et al. A dose titration, and an open 6-week efficacy and safety study of desmopressin tablets in the management of nocturnal enuresis. J Urol 1994 Feb; 151(2): 460–3PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Johan Van de Walle
    • 1
  • Charlotte Van Herzeele
    • 1
  • Ann Raes
    • 1
  1. 1.Department of Pediatric NephrologyUniversity Hospital GhentGhentBelgium

Personalised recommendations