Desmopressin and oxybutynin in monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial and an assessment of predictive factors

Authors


Roberto Del Gado, Department of Pediatrics, Second University of Naples, Via L. De Crecchio 4, Naples, 80131, Italy. e-mail: uniplan@hotmail.it

Abstract

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

The desmopressin analogue to antidiuretic vasopressin is an evidence-based therapy but conflicting results are provided regarding the initial dose of oral desmopressin. Previous studies report the use of a combined therapy with desmopressin and oxybutynin to treat desmopressin-resistant monosymptomatic nocturnal enuresis. These studies show promising results, but they suffer from lack of randomization and lack of a placebo-controlled patient group and are of small sample size. In addition to this, no predictive factors of response to the combined therapy have been considered.

This study showed no significant difference between either a 120 µg or a 240 µg desmopressin initial dose with regard to degree of response. The study is the first randomized, double-blinded, placebo-controlled trial showing the efficacy of combination therapy with desmopressin plus oxybutynin for monosymptomatic nocturnal enuresis. Furthermore, bladder volume and wall thickness index, nocturnal polyuria and voiding latency were assessed as predictive factors of response to the therapy.

OBJECTIVES

  • • To assess the efficacy of desmopressin plus oxybutynin and compare two starting dosages of desmopressin (120 and 240 µg) in a randomized, double-blinded, placebo-controlled trial for children with monosymptomatic nocturnal enuresis (MNE) resistant to desmopressin.
  • • The predictive factors of children with MNE responsive to desmopressin and combination therapy were also evaluated.

PATIENTS AND METHODS

  • • Our sample included 206 patients aged between 6 and 13 (mean age 10.6 ± 2.9 years), 117 males. All patients were required to have MNE.
  • • The patients were randomly divided into two groups: the first group was given oral melt 120 µg and the second group 240 µg, for 2 weeks.
  • • All patients who had experienced failure of treatment with sublingually administered desmopressin alone were given either desmopressin plus 5 mg oxybutynin or desmopressin plus placebo in a randomized, double-blinded trial for 4 weeks.
  • • As predictive factors, bladder volume and wall thickness index, nocturnal polyuria and voiding latency were considered.

RESULTS

  • • There was no significant difference between the 120 µg and 240 µg patients in terms of response.
  • • The oxybutynin group showed a higher rate of full and partial responses (45% success) compared with the placebo group (17% success), P < 0.01.
  • • The responders to combined oxybutynin and desmopressin had significantly lower bladder volume and wall thickness index than the other patients.

CONCLUSIONS

  • • Our findings highlight that anticholinergic agents may play an important role for a subset of children with enuresis who have a restricted bladder capacity and thickened bladder wall.
  • • Ultrasonography-measured bladder variables can provide useful predictive clues for MNE.
  • • Predictive factors can help to differentiate treatment subtypes and guide clinical management in primary nocturnal enuresis.

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