Night-time bedwetting is common in childhood, and can cause stigma, stress and inconvenience. The review examined 58 trials of tricyclic drugs which included 3721 children. Tricyclics are antidepressants, but probably work because of one of their side effects (affecting the messages sent to the bladder by the nerves). The one most commonly used is imipramine, which can be used for up to three months. Tricyclic drugs reduce bedwetting by about one wet night per week while being used and about a fifth of the children become dry. However, they do not work once the children stop using them. Compared with the other commonly used drug, desmopressin, tricyclics are less expensive but have more side-effects. A particular concern is tricyclic overdose, which can be serious. Bed alarms are more expensive than tricyclics and more bother to families to use but about half the children remain dry after alarm treatment has finished, and they do not have the side-effects of the drugs.
Although tricyclics and desmopressin are effective in reducing the number of wet nights while taking the drugs, most children relapse after stopping active treatment. In contrast, only half the children relapse after alarm treatment. Parents should be warned of the potentially serious adverse effects of tricyclic overdose when choosing treatment. Further research is needed into comparisons between drug and behavioural or complementary treatments, and should include relapse rates after treatment is finished.
Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2% of young adults.
To assess the effects of tricyclic and related drugs on nocturnal enuresis in children, and to compare them with other interventions.
We searched the Cochrane Incontinence Group Specialised Register of trials (searched 19 June 2007) and the reference lists of relevant articles including two previously published versions of this review.
All randomised and quasi-randomised trials of tricyclics or related drugs for nocturnal enuresis in children were included in the review. Comparison interventions included placebo, other drugs, alarms, behavioural methods or complementary/miscellaneous interventions. Trials focused solely on daytime wetting were excluded.
Two reviewers independently assessed the quality of the eligible trials, and extracted data.
Fifty eight randomised trials met the inclusion criteria, involving 3721 children. The quality of many of the trials was poor. Most comparisons or outcomes were addressed only by single trials.
Treatment with most tricyclic drugs (such as imipramine, amitriptyline, viloxazine, nortriptyline, clomipramine and desipramine) was associated with a reduction of about one wet night per week while on treatment (e.g. imipramine compared with placebo, weighted mean difference (WMD) -0.92, 95% CI -1.38 to -0.46). The exception was mianserin, where results from one small trial did not reach statistical significance. About a fifth of the children became dry while on treatment (relative risk for failure (RR) 0.77, 95% CI 0.72 to 0.83), but this effect was not sustained after treatment stopped (e.g. imipramine (190/199, 96%) versus placebo (210/217, 97%): RR 0.98, 95% CI 0.95 to 1.03). There was not enough information to assess the relative performance of one tricyclic against another, except that imipramine was better than mianserin. The evidence comparing desmopressin with tricyclics was unreliable or conflicting, but in a Cochrane review of desmopressin, almost all the children failed or relapsed after stopping active treatment with desmopressin.
The evidence comparing tricyclics with alarms was also unreliable or conflicting during treatment. In one small trial all the children failed or relapsed after tricyclics stopped, compared with about half after alarms. This result was compatible with the results in the Cochrane review of alarm treatment, which found that about half the children remained dry after alarm treatment was finished. There was a little evidence from single trials to suggest that imipramine might be better than a simple reward system with star charts during treatment; worse than a complex intervention involving education, counselling, waking and retention control training; better than a restricted diet; and worse than hypnosis. However, these results need to be confirmed by further research.