title: Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics).
abstract: BACKGROUND
  Enuresis (bedwetting) is a socially stigmatising and stressful condition which affects around 15% to 20% of five-year olds and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. Drugs (including desmopressin, tricyclics and other drugs) have often been tried to treat nocturnal enuresis.
  
  
  OBJECTIVE
  To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children and to compare them with other interventions.
  
  
  METHODS
  We searched the Cochrane Incontinence Group Specialised Register of trials (searched 15 December 2011), which includes searches of MEDLINE and CENTRAL, to identify published and unpublished randomised and quasi-randomised trials. The reference lists of relevant articles were also searched.
  
  
  METHODS
  All randomised trials of drugs (excluding desmopressin or tricyclics) for treating nocturnal enuresis in children up to the age of 16 years were included in the review. Trials were eligible for inclusion if children were randomised to receive drugs compared with placebo, other drugs or behavioral interventions for nocturnal enuresis. Studies which included children with daytime urinary incontinence or children with organic conditions were also included in this review if the focus of the study was on nocturnal enuresis. Trials focused solely on daytime wetting and trials of adults with nocturnal enuresis were excluded.
  
  
  METHODS
  Two review authors independently assessed the quality of the eligible trials and extracted data. Differences between review authors were settled by discussion with a third review author.
  
  
  RESULTS
  A total of 40 randomised or quasi-randomised controlled trials (10 new in this update) met the inclusion criteria, with a total of 1780 out of 2440 children who enrolled receiving an active drug other than desmopressin or a tricyclic. In all, 31 different drugs or classes of drugs were tested. The trials were generally small or of poor methodological quality. There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus placebo, when compared to placebo indomethacin (risk ratio [RR] 0.36, 95% CI 0.16 to 0.79), diazepam (RR 0.22, 95% CI 0.11 to 0.46), mestorelone (RR 0.32, 95% CI 0.17 to 0.62) and atomoxetine (RR 0.81, 95% CI 0.70 to 0.94) appeared to reduce the number of children failing to have 14 consecutive dry nights. Although indomethacin and diclofenac were better than placebo during treatment, they were not as effective as desmopressin and there was a higher chance of adverse effects. None of the medications were effective in reducing relapse rates, although this was only reported in five placebo controlled trials.For drugs versus drugs, combination therapy with imipramine and oxybutynin was more effective than imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.94) and also had significantly lower relapse rates than imipramine monotherapy (RR 0.35, 95% CI 0.16 to 0.77). There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus behavioural therapy, bedwetting alarms were found to be better than amphetamine (RR 2.2, 95% CI 1.12 to 4.29), oxybutynin (RR 3.25, 95% CI 1.77 to 5.98), and oxybutynin plus holding exercises (RR 3.3, 95% CI 1.84 to 6.18) in reducing the number of children failing to achieve 14 consecutive dry nights.Adverse effects of drugs were seen in 19 trials while 17 trials did not adequately report the occurrence of side effects.
  
  
  CONCLUSIONS
  There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials.
authors.affiliation: Department of Surgery and Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Australia.
authors.forename: Aniruddh V
authors.initials: AV
authors.lastname: Deshpande
authors.forename: Patrina H Y
authors.initials: PH
authors.lastname: Caldwell
authors.forename: Premala
authors.initials: P
authors.lastname: Sureshkumar
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D050034:Antidiuretic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D056902:Clinical Alarms / Q000009:adverse effects; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D053206:Nocturnal Enuresis / Q000188:drug therapy* / Q000517:prevention & control; D011619:Psychotropic Drugs / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D050034:Antidiuretic Agents; D018680:Cholinergic Antagonists; D011619:Psychotropic Drugs