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.
Objectives
To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children and to compare them with other interventions.
Search 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of trials (searched 15 December 2011), which includes searches of MEDLINE and CENTRAL, to identify published and unpublished randomised and quasi‐randomised trials.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.
Selection criteria
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.
Data collection and analysis
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.
Main 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 There was an overall paucity of data regarding outcomes after treatment was withdrawn.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.
Authors' 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.
PICOs
Plain language summary
Drug treatment for children with bedwetting (nocturnal enuresis) but not including the drug types desmopressin or tricyclics
Bedwetting (nocturnal enuresis) is the involuntary loss of urine at night without an underlying organic disease as the cause. It can result in social problems, sibling teasing and lowered self esteem. It affects around 15% to 20% of five‐year olds, and up to 2% of adults. Many different types of drugs have been used to treat children with bed wetting. There is not enough reliable evidence to show that drugs other than desmopressin or tricyclics reduce bedwetting in children during treatment when used in isolation, despite their risk of unwanted side effects. In other Cochrane reviews, alarms triggered by wetting, desmopressin and tricyclic drugs have been shown to work during treatment. However, alarms have a more sustained effect than desmopressin and tricyclics after treatment has finished. The adverse effects of alarm therapy (tiredness and waking other members of the family) are relatively benign and self limiting compared with the adverse effects of drugs. One class of drugs (anticholinergic drugs) appears to improve the efficacy of other established treatments such as tricyclics, bedwetting alarms and desmopressin. The cost of treating children with bedwetting with alarm therapy or drugs may vary in different countries.
