Tricyclic and related drugs for nocturnal enuresis in children

Enuresis (bedwetting) is a socially unacceptable and stressful condition which affects around 15-20% 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.

To assess the effects of tricyclic and related drugs on nocturnal enuresis in children, and to compare them with other interventions.

The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997.

All randomised trials of tricyclic and related drugs for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive tricyclics compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were provided. Trials focused solely on daytime wetting were excluded.

Two reviewers independently assessed the quality of the eligible trials, and extracted data.

Twenty two randomised trials, involving 1100 children treated with tricyclic or related drugs, met the inclusion criteria. The quality of many of the trials was poor. Only single trials compared tricyclic or related drugs with each other, other drugs, desmopressin, alarms or other behavioural interventions. Treatment with tricyclic drugs (such as imipramine, amitriptyline, viloxazine, clomipramine and desipramine but not mianserin) were associated with a reduction of about one wet night per week while on treatment (eg using imipramine, WMD -0.99, 95% CI -1.27 to -0.71). Children were almost five times more likely to achieve 14 dry nights with the drugs (eg using imipramine, RR = 4.99, 95% CI 2.4 to 10.40). Desmopressin and tricyclics appeared equally effective while on treatment, but this effect was not sustained after treatment stopped. There was no detectable difference between imipramine and alarms while on treatment, but afterwards those who had used alarms had one fewer wet night per week (WMD 1.03, 95% CI 0. 19 to 1.87).

Treatment with tricyclic drugs (imipramine, amitriptyline, viloxazine, clomipramine and desipramine but not mianserin) was associated with a reduction of about one wet night per week while on treatment, but long term effectiveness is unknown. Desmopressin and tricyclics appeared equally effective while on treatment, but this effect was not sustained after treatment stopped. Alarms may be more effective in the long term. Comparisons between drug and behavioural treatments are needed, and should include relapse rates after treatment is finished.