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BMJ Clin Evid. 2007; 2007: 0305.
Published online 2007 October 1.
PMCID: PMC2943787

Nocturnal enuresis

Please enter your position here Darcie Kiddoo, Please enter your honorific or qualification details of medical background here, Assistant Professor

Abstract

Introduction

Nocturnal enuresis affects 15−20% of 5-year-old children, 5% of 10 year-old-children and 1−2% of people aged 15 years and over. Without treatment, 15% of affected children will become dry each year. Nocturnal enuresis is not diagnosed in children younger than 5 years, and treatment may be inappropriate for children younger than 7 years.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions for relief of symptoms? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, anticholinergics (oxybutynin, tolterodine, hyoscyamine), desmopression, dry bed training, enuresis alarm, hypnotherapy, standard home alarm clock, tricyclics (imipramine, desipramine).

Key Points

Nocturnal enuresis affects 15−20% of 5-year-old children, 5% of 10-year-old children, and 1−2% of people aged 15 years and over. Without treatment, 15% of affected children will become dry each year.

  • Nocturnal enuresis is not diagnosed in children younger than 5 years, and treatment may be inappropriate for children younger than 7 years.

Enuresis alarms increase the number of dry nights compared with no treatment, and may be more effective than tricyclic drugs at reducing treatment failure and relapse.

  • Combining the use of alarms with dry bed training may increase the number of dry nights, but we don't know whether adding tricyclic drugs to alarms is also beneficial.

We don't know whether using an alarm clock set to wake the child before the time of likely enuresis is more likely to lead to dry nights compared with waking every 3 hours.

Desmopressin and tricyclic drugs reduce the number of wet nights compared with placebo, but they seem not to be effective once treatment is discontinued, and they can cause adverse effects which, in the case of tricyclic drugs, include potentially fatal overdose.

  • We don't know whether desmopressin is more or less effective at reducing wet nights than tricyclic drugs or enuresis alarms.
  • An alert has been issued in the UK regarding rare but serious adverse effects including hyponatraemia, water intoxication, and convulsions associated with desmopressin nasal spray, and the primary nocturnal enuresis indication has been withdrawn from the nasal spray in the UK.

We don't know whether dry bed training, anticholinergic drugs,acupuncture or laser acupuncture,or hypnotherapy are effective at increasing dry nights, or how they compare with other treatments.

About this condition

Definition

Nocturnal enuresis is the involuntary discharge of urine at night in a child aged 5 years or older in the absence of congenital or acquired defects of the central nervous system or urinary tract. Disorders that have bedwetting as a symptom (termed "nocturnal incontinence") can be excluded by a thorough history, examination, and urinalysis. "Monosymptomatic" nocturnal enuresis is characterised by night time symptoms only and accounts for 85% of cases. Nocturnal enuresis is defined as primary if the child has not been dry for a period of more than 6 months, and secondary if such a period of dryness preceded the onset of wetting. Most management strategies are aimed at children aged 7 years and older.

Incidence/ Prevalence

Between 15% and 20% of 5-year-olds, 7% of 7-year-olds, 5% of 10-year-olds, 2-3% of 12-14-year-olds, and 1-2% of people aged 15 years and over wet the bed twice a week on average.

Aetiology/ Risk factors

Nocturnal enuresis is associated with several factors, including small functional bladder capacity, nocturnal polyuria, and, most commonly, arousal dysfunction. Linkage studies have identified associated genetic loci on chromosomes 8q, 12q, 13q, and 22q11.

Prognosis

Nocturnal enuresis has widely differing outcomes, from spontaneous resolution to complete resistance to all current treatments. About 1% of children remain enuretic until adulthood. Without treatment, about 15% of children with enuresis become dry each year. We found no RCTs on the best age at which to start treatment in children with nocturnal enuresis. Anecdotal experience suggests that reassurance is sufficient below the age of 7 years. Behavioural treatments, such as moisture or wetting alarms, require motivation and commitment from the child and a parent. Anecdotal experience suggests that children under the age of 7 years may not exhibit the commitment needed.

Aims of intervention

To stay dry on particular occasions (e.g. when visiting friends); to reduce the number of wet nights; to reduce the impact of the enuresis on the child's lifestyle; to initiate successful continence; to avoid relapse, with minimal adverse effects.

Outcomes

Rate of initial success (defined as 14 consecutive dry nights); average number of wet nights a week; number of relapses after initial success; average number of wet nights after treatment has ceased.

Methods

BMJ Clinical Evidence search and appraisal March 2007. The following databases were used to identify studies for this review: Medline 1966 to March 2007, Embase 1980 to March 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for assessment in this chapter were: published systematic reviews and RCTs in any language, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the chapter as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table
GRADE evaluation of interventions for Nocturnal enuresis

Glossary

Dry bed training
A multicomponent behavioural programme for treatment of nocturnal enuresis in children. Elements of the programme are directed at increasing bladder capacity, strengthening the sphincter, and encouraging rapid movement from bed to toilet.
High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Very low-quality evidence
Any estimate of effect is very uncertain.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

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2. Blackwell C. A guide to enuresis: a guide to treatment of enuresis for professionals. Bristol: Eric, 1989.
3. Eiberg H. Total genome scan analysis in a single extended family for primary nocturnal enuresis: evidence for a new locus (ENUR 3) for primary nocturnal enuresis on chromosome 22q11. Eur Urol 1998;33:34–36. [PubMed]
4. Eiberg H. Nocturnal enuresis is linked to a specific gene. Scand J Urol Nephrol 1995;173(suppl):15–17. [PubMed]
5. Arnell H, Hjalmas M, Jagervall G, et al. The genetics of primary nocturnal enuresis: inheritance and suggestion of a second major gene on chromosome 12q. J Med Genet 1997;34:360–365. [PMC free article] [PubMed]
6. Eiberg H, Berendt I, Mohr J. Assignment of dominant inherited nocturnal enuresis (ENUR 1) to chromosome 13q. Nat Genet 1995;10:354–356. [PubMed]
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8. Glazener CMA, Evans JHC. Desmopressin for nocturnal enuresis in children. In: The Cochrane Library, Issue 1, 2007. Chichester, UK: John Wiley & Sons. Search date 2006; primary sources Medline, Embase, Amed, Assia, Bids, Cinahl, Psychlit, Sigle, and Department of Health and Social Services (DHSS) data.
9. Unüvar T, Sönmez F. The role of urine osmolality and ions in the pathogenesis of primary enuresis nocturna and in the prediction of responses to desmopressin and conditioning therapies. Int Urol Nephrol 2005;37:751–757. [PubMed]
10. Muller D, Roehr CC, Eggert P. Comparative tolerability of drug treatments for nocturnal enuresis in children. Drug Safety 2004;27:717–727. [PubMed]
11. Robson WL, Leung AK. Side effects and complications of treatment with desmopressin for enuresis. J Natl Med Assoc 1994;86:775–778. [PMC free article] [PubMed]
12. Naitoh Y, Kawauchi A, Yamao Y, et al. Combination therapy with alarm and drugs for monosymptomatic nocturnal enuresis not superior to alarm monotherapy. Urology 2005;66:632–635. [PubMed]
13. Glazener CMA, Evans JHC, Peto RE. Complex behavioural and educational interventions for nocturnal enuresis in children. In: The Cochrane Library, Issue 1, 2007. Chichester, UK: John Wiley & Sons. Search date 2005; primary sources Medline, Cinahl, and Cochrane Central Register of Controlled Trials.
14. Glazener CMA, Evans JHC, Peto RE. Alarm interventions for nocturnal enuresis in children. In: The Cochrane Library, Issue 1, 2007. Chichester, UK: John Wiley & Sons. Search date 2004; primary sources Medline, Cinahl, and Cochrane Central Register of Controlled Trials.
15. Glazener CMA, Evans JHC, Peto RE. Tricyclic and related drugs for nocturnal enuresis in children. In: The Cochrane Library, Issue 1, 2007. Chichester, UK: John Wiley & Sons. Search date 2005, primary sources Medline, Cinahl, and Cochrane Central Register of Controlled Trials.
16. Glazener CMA, Evans JHC, Peto RE. Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics). In: The Cochrane Library, Issue 1, 2007. Chichester, UK: John Wiley & Sons. Search date 2005; primary sources Medline, Cinahl, and Cochrane Central Register of Controlled Trials.
17. Rushton HG, Belman AB, Zaontz MR, et al. The influence of small functional bladder capacity and other predictors on the response of desmopressin in the management of monosymptomatic nocturnal enuresis. J Urol 1996;156:651–655. [PubMed]
18. Glazener CM, Evans JH, Cheuk DK. Complementary and miscellaneous interventions for nocturnal enuresis in children. In: The Cochrane Library, Issue 1, 2007. Chichester, UK: John Wiley & Sons. Search date 2004; primary sources Medline, Cinahl, and Cochrane Central Register of Controlled Trials.
19. Radmayr C, Schlager A, Studen M, et al. Prospective randomised trial using laser acupuncture versus desmopressin in the treatment of nocturnal enuresis. Eur Urol 2001;40:201–205. [PubMed]
20. El-Anany FG, Maghraby HA, Shaker SED, et al. Primary nocturnal enuresis: a new approach to conditioning treatment. Urology 1999;53:405–409. [PubMed]
21. Edwards SD, van der Spuy HI. Hypnotherapy as a treatment for enuresis. J Child Psychol Psychiat 1985;26:161–170. [PubMed]
2007; 2007: 0305.
Published online 2007 October 1.

Desmopressin (while treatment continues)

Summary

REDUCTION OF ENURESIS Compared with placebo: Desmopression is more effective than placebo at reducing wet nights while treatment continues ( moderate-quality evidence ). Compared with enuresis alarm: Desmopressin may be no more effective at reducing the number of wet nights, or at achieving 14 consecutive dry nights at 3–6 months while treatment continues, compared with an enuresis alarm ( low-quality evidence ). Compared with conditioning therapy: Intranasal desmopressin may be no more effective at reducing wet nights while treatment continues compared with conditioning therapy, such as fluid restriction, waking to an alarm once at night, and recording events on a calendar (low-quality evidence). Compared with laser acupuncture: Desmopressin may be no more effective than laser acupuncture at reducing wet nights at 6 months (low-quality evidence). Compared with tricyclic drug: s We don't know whether desmopressin is more effective at reducing wet nights than the tricyclic drugs amitripytine, and imipramine (low-quality evidence). High dose compared with low dose: We don't know whether high-dose desmopressin leads to greater improvement in enuresis compared with low-dose desmopressin ( moderate-quality evidence ). NOTE We found no clinically important results about desmopressin compared with desmopressin plus the anticholinergic drugs oxybutynin, tolterodine, and hyoscyamine in the treatment of children with nocturnal enuresis.

Benefits

Desmopressin versus placebo:

We found one systematic review (search date 2006), which compared desmopressin versus placebo. It found that desmopressin (10–60 µg) significantly reduced the number of wet nights a week during treatment (duration not reported) compared with placebo (e.g. desmopressin 20 µg v placebo: 12 RCTs, 813 children, WMD –1.34, 95% CI –1.57 to –1.11; desmopressin 40 µg v placebo: 6 RCTs, 424 children, WMD –1.33, 95% CI –1.67 to –0.99). The review found that desmopressin significantly increased the rate of initial success (14 consecutive dry nights) during treatment compared with placebo (e.g. RR for failure to achieve 14 consecutive dry nights with desmopressin 20 µg v placebo, 5 RCTs, 288 children, RR 0.84, 95% CI 0.79 to 0.91; RR for failure to achieve 14 consecutive dry nights with desmopressin 40 µg v placebo, 6 RCTs, 263 children, RR 0.81, 95% CI 0.74 to 0.88see table 1 ).

Table 1
Treatments for enuresis: advantages and disadvantages (see text).

Desmopressin versus tricyclic drugs:

We found one systematic review (search date 2006, 4RCTs), which compared desmopressin versus tricyclic drugs. The review concluded that the four trials comparing desmopressin versus tricyclics were too small to provide definitive results. However, one RCT included in the review (31 children) found a significant reduction in number of wet nights with amitriptyline compared with desmopressin (WMD in wet nights 1.40, 95% CI 0.12 to 2.68). It found no significant difference in treatment success rates (RR for treatment failure 1.20, 95% CI 0.89 to 1.61). The review found no significant difference between desmopressin and imipramine in the number of wet nights at the end of treatment (3 RCTs, 300 children, WMD in wet nights –0.11, 95% CI –0.62 to +0.41), while significantly more children achieved dry nights with desmopressin compared with imipramine (RR for failure to achieve 14 dry nights: 2 RCTs, 103 children, RR 0.44, 95% CI 0.27 to 0.73) but there was no infomation about subsequent relapse.

Desmopressin versus placebo or conditioning therapy:

We found one small RCT (55 children with primary monosymptomatic enuresis aged 5 years to 15 years) which compared intranasal desmopressin, placebo, and conditioning therapy. The conditioning therapy included fluid restriction, waking to an alarm once a night, and recording events on a calendar. The RCT found that a complete response (defined as a greater than 85% reduction in wet nights) was found in 60% of people with intranasal desmopressin, 30% with conditioning, and 13.3% with placebo (absolute numbers not provided; results presented graphically). It found that desmopressin significantly improved response rate compared with placebo (P = 0.02), and found no significant difference in response rate between desmopressin and conditioning (P = 0.124). The RCT reported a 6.25% relapse rate after stopping desmopressin.

Desmopressin versus laser acupuncture:

See benefits of laser acupuncture.

Lower versus higher doses of desmopressin:

We found one systematic review (search date 2006, 8 RCTs; see comment below), which compared different doses of desmopressin. It found limited evidence that higher doses reduced the number of wet nights during treatment (duration not reported) compared with lower doses (wet nights with desmopressin 20 µg v desmopressin 60 µg; WMD 0.72, 95% CI 0.3 to 0.14). However, there was no difference between doses in the initial success rate (14 consecutive dry nights) during treatment.

Desmopressin plus anticholinergics:

We found no systematic review or RCTs.

Harms

The systematic review reported some adverse effects after treatment with desmopressin (5.3/100 people), including nasal discomfort, headache, nosebleeds, bad taste, rash, sight disturbance, and anorexia. Other reported adverse effects include other gastrointestinal symptoms, cough, and sore throat. Rarely, water intoxication has been reported. The additional RCT comparing enuresis alarm alone versus desmopressin plus alarm gave no information on adverse effects.The RCT comparing intranasal desmopressin, conditioning therapy, and placebo did not report on harms.At the request of the Medicines and Healthcare Products Regulatory Agency (MHRA), the indication for the treatment of primary nocturnal enuresis has been removed from desmopressin nasal spray in the UK (www.mhra.gov.uk). The safety information noted that, in comparison with oral formulations of desmopressin, nasal forms were associated with the majority of serious adverse drug reactions (including rare, serious reactions such as hyponatraemia, water intoxication, and convulsions), and, as the risk–benefit profile of the oral formulations was more favourable than the nasal spray, the nasal form should no longer be used for primary nocturnal enuresis in adults or children.

Comment

The systematic review included only studies of interventions used to remedy either primary or secondary nocturnal enuresis (incontinence was excluded by medical examination or explicitly mentioned in the inclusion/exclusion criteria of included RCTs), and included a systematic measurement of baseline wetting (with 1 exception) and outcomes. Many of the included RCTs were of poor quality.

Substantive changes

Desmopressin One already-included systematic review updated, and one RCT comparing desmopressin versus placebo or conditioning therapy added;benefits and harms data enhanced, categorisation of "desmopressin (while treatment continues)" as Beneficial, "desmopressin (after treatment discontinuation)" as Unlikely to be beneficial, and "desmopressin plus enuresis alarm (unclear if more effective than alarm alone)" as Unknown effectiveness, all unchanged.

2007; 2007: 0305.
Published online 2007 October 1.

Desmopressin (after treatment discontinuation)

Summary

RELAPSE RATES Compared with placebo: Desmopressin seems to be less effective than placebo at reducing relapse rates after discontinuation of treatment ( moderate-quality evidence ). Compared with an enuresis alarm: Desmopressin may be less effective than an enuresis alarm at reducing relapse rates after discontinuation of treatment ( low-quality evidence ).

Benefits

Desmopressin versus placebo:

We found one systematic review (search date 2006), which compared desmopressin versus placebo. Four small RCTs included in the review found that treatment success was not sustained after discontinuation. The review did not perform a meta-analysis of post-treatment effects because of poor study quality.

Desmopressin versus enuresis alarm:

We found one systematic review (search date 2006, 4RCTs). The review found no significant difference between desmopressin and alarm in the number of children achieving success during treatment (14 consecutive dry nights) after 3–6 months (3 RCTs, 270 children, RR for failure 1.07, 95% CI 0.83 to 1.36). However, one RCT (50 children) included in the review found that desmopressin significantly reduced the number of wet nights a week during the first week of treatment (WMD in wet nights –1.70, 95% CI –2.95 to –0.45) compared with alarm, although it found that, after 3 months of treatment, there were fewer wet nights with alarm (WMD in wet nights 1.40, 95% CI 0.14 to 2.66). Two small RCTs included in the review found that the relapse rate was significantly less after the end of alarm treatment compared with desmopressin (number failing to achieve 14 consecutive dry nights or relapsing after cure: 40/62 [65%] with desmopressin v 26/57 [46%] after alarm, RR 1.42, 95% CI 1.05 to 1.91).

Harms

See harms of desmopressin during treatment.

Comment

None.

Substantive changes

2007; 2007: 0305.
Published online 2007 October 1.

Desmopressin plus enuresis alarm

Summary

REDUCTION OF ENURESIS Compared with an enuresis alarm alone: We don’t know whether desmopressin plus an enuresis alarm is more effective at reducing wet nights, or at achieving 14 consecutive dry nights, compared with an enuresis alarm alone ( very low-quality evidence ). RELAPSE RATES Compared with an enuresis alarm alone: We don’t know whether desmopressin plus an enuresis alarm may be more effective at reducing relapse rates compared with an enuresis alarm alone ( very low-quality evidence ).

Benefits

Desmopressin plus enuresis alarm:

We found one systematic review (search date 2006, 6RCTs, see comment below) and one additional RCT comparing desmopressin plus enuresis alarm versus alarm alone. The review found that desmopressin plus alarm reduced the number of wet nights per week during treatment compared to alarm alone or alarm plus placebo (4 RCTs, 380 children, WMD in wet nights –0.83, 95% CI –1.11 to –0.55), but it found no significant difference between desmopressin plus alarm and alarm alone or alarm plus placebo in treatment success rate during treatment (failing to achieve 14 consecutive dry nights during treatment: 5 RCTs, 286 children, RR 0.88, 95% CI 0.73 to 1.05). It also found that, after treatment stopped, there was no significant difference between desmopressin plus alarm and alarm plus placebo or alarm alone in the combined failure or relapse rate (failing to achieve 14 consecutive dry nights or relapsing after cure: 4 RCTs, 427 children, RR 0.91, 95% CI 0.78 to 1.08). The review noted that some included trials were small, one was a crossover with a short duration of treatment, and follow-up results were not available for two included RCTs.The additional RCT compared three treatments: enuresis alarm alone, desmopressin plus alarm, and alarm plus imipramine. It found no significant difference in the reduction in frequency of wet nights during treatment with desmopressin plus alarm compared with alarm alone over 6 months (3-arm RCT; 105 children with monosymptomatic, primary nocturnal enuresis; mean reduction in nights per 2 weeks with enuresis: 8.1 with desmopressin plus alarm v 6.9 with alarm alone; difference reported as not significant, P value not reported). After 6 months, there was no statistically significant difference in improvement in enuresis frequency with desmopressin plus alarm compared with alarm alone (improvement defined as at least 50% reduction in enuretic nights; AR for improvement: 28/35 [80%] with desmopressin plus alarm v 22/37 [59%] with alarm alone; P = 0.059). After 6 months, a higher proportion of children had one or fewer enuretic nights per 2 weeks with alarm alone than with desmopressin plus alarm; however, the significance of this difference was not reported (AR: 7/35 [20%] with desmopressin plus alarm v 11/37 [30%] with alarm alone; significance assessment not performed). In children who achieved one or fewer enuretic nights per 2 weeks, treatment was stopped. There was a higher rate of relapse after stopping treatment in those who had received desmopressin plus alarm compared with alarm alone (43% with desmopressin plus alarm v 0% with alarm alone; significance assessment not performed).

Harms

See harms of desmopressin during treatment.

Comment

None.

Substantive changes

2007; 2007: 0305.
Published online 2007 October 1.

Dry bed training

Summary

REDUCTION OF ENURESIS Compared with no treatment: Dry bed training is no more effective than no treatment at achieving 14 consecutive dry nights at 8–24 weeks ( moderate-quality evidence ). Compared with enuresis alarm: Dry bed training is no more effective at increasing treatment success rates at 4–20 weeks compared with an enuresis alarm ( high-quality evidence ). RELAPSE RATES Compared with no treatment: Dry bed training is no more effective at reducing relapse rates at the end of treatment compared with no treatment (moderate quality evidence). Compared with enuresis alarm: Dry bed training is less effective than an enuresis alarm at reducing relapse rates at the end of treatment (moderate-quality evidence).

Benefits

Dry bed training versus no treatment:

We found one systematic review (search date 2005, 3 RCTs, 144 children; see comment below), which compared dry bed training versus no treatment. The review found no significant difference in treatment success rates (numbers achieving 14 consecutive dry nights) between dry bed training and control during treatment lasting 8–24 weeks (2 RCTs, RR for failure 0.82, 95% CI 0.66 to 1.02). One RCT included in the review found no significant difference in numbers failing or relapsing after treatment ended (RR for failure or relapse 0.85, 95% CI 0.71 to 1.02) (see table 1 ).

Dry bed training versus enuresis alarm:

We found one systematic review (search date 2004, 3 RCTs), which compared dry bed training versus use of an enuresis alarm. The review found no significant difference in effectiveness in treatment success during treatment lasting 4–20 weeks between enuresis alarm and dry bed training (3 RCTs, RR for failure during treatment 1.33, 95% CI 0.79 to 2.24). One small RCT (40 children) included in the review found that fewer children failed treatment or relapsed after treatment had ended with use of an alarm compared with dry bed training (RR for failure or relapse 0.59, 95% CI 0.37 to 0.95).

Harms

The systematic reviews did not report on harms of dry bed training.

Comment

Dry bed training versus no treatment:

The RCTs comparing dry bed training versus control were small and may have been underpowered to detect a clinically significant difference between treatment groups.

Substantive changes

No new evidence

2007; 2007: 0305.
Published online 2007 October 1.

Dry bed training plus enuresis alarm

Summary

REDUCTION OF ENURESIS Compared with no treatment: Dry bed training plus an enuresis alarm is no more effective than treatment at achieving 14 consecutive dry nights ( moderate-quality evidence ). Compared with an enuresis alarm alone: Dry bed training plus an enuresis alarm is no more effective than an enuresis alarm alone at reducing wet nights or at achieving 14 consecutive dry nights ( high-quality evidence ). RELAPSE RATES Compared with no treatment: Dry bed training plus an enuresis alarm is no more effective at reducing relapse rates at the end of treatment compared with no treatment (moderate-quality evidence). Compared with alarm alone: Dry bed training plus an enuresis alarm is no more effective than an alarm alone at reducing relapse rates after treatment is discontinued (moderate-quality evidence).

Benefits

Enuresis alarm plus dry bed training versus no treatment:

We found one systematic review (search date 2005, 3 RCTs, 144 children; see comment below), which compared dry bed training versus no treatment. The review found no significant difference in treatment success rates (numbers achieving 14 consecutive dry nights) between dry bed training and control during treatment lasting 8–24 weeks (2 RCTs, RR for failure 0.82, 95% CI 0.66 to 1.02). One RCT included in the review found no significant difference in numbers failing or relapsing after treatment ended (RR for failure or relapse 0.85, 95% CI 0.71 to 1.02) (see table 1 ).

Enuresis alarm plus dry bed training versus alarm alone:

We found one systematic review (search date 2004, 5 RCTs), which compared alarms augmented with dry bed training versus alarms alone. It found no significant difference in number of wet nights during treatment between alarm alone and alarm treatment augmented with dry bed training (2 RCTs, 43 children, WMD in wet nights +1.00, 95% CI –0.20 to +2.20). The review found no significant difference in treatment success (numbers achieving 14 consecutive dry nights) between alarm treatment alone and augmented alarm treatment, or in numbers relapsing after treatment was discontinued (treatment success: 5 RCTs, 234 children, RR 1.21, 95% CI 0.82 to 1.81; failure or relapse: 3 RCTs, 152 children, RR for failure or relapse 1.29, 95% CI 0.94 to 1.77).

Harms

The systematic reviews did not report on harms of dry bed training.

Comment

None.

Substantive changes

No new evidence

2007; 2007: 0305.
Published online 2007 October 1.

Enuresis alarm

Summary

REDUCTION OF ENURESIS Compared with no treatment: An enuresis alarm is more effective than no treatment at reducing wet nights, or at achieving 14 consecutive dry nights at 10–20 weeks ( high-quality evidence ). Compared with desmopressin: An enuresis alarm may be no more effective than desmopressin at reducing the number of wet nights or at achieving 14 consecutive dry nights at 3–6 months while treatment continues ( low-quality evidence ). Plus dry bed training compared with no treatment: An enuresis alarm plus dry bed training is more effective at reducing wet nights than no treatment ( moderate-quality evidence ). Plus dry bed training compared with enuresis alarm alone: An enuresis alarm plus dry bed training is no more effective than an enuresis alarm alone at reducing wet nights, or at achieving 14 consecutive dry nights (high-quality evidence). Plus desmopressin compared with an enuresis alarm alone: We don’t know whether an enuresis alarm plus desmopressin is more effective than an enuresis alarm alone at reducing wet nights or achieving 14 consecutive dry nights ( very low-quality evidence ). Compared with tricyclic drugs: An enuresis alarm is more effective than tricyclic drugs at achieving 14 consecutive dry nights at 8–14 weeks (high-quality evidence). Plus tricylics compared with alarm alone: An enuresis alarm plus the tricyclic drug imipramine may be no more effective than an enuresis alarm alone at reducing wet nights at 6 months (low-quality evidence). Compared with dry bed training: An enuresis alarm is no more effective than dry bed training at increasing treatment success rates at 4–20 weeks (high-quality evidence). RELAPSE RATES Compared with no treatment: An enuresis alarm is more effective at reducing relapse rates at the end of treatment compared with control (high-quality evidence). Compared with desmopressin: An enuresis alarm may be more effective than desmopressin at reducing relapse rates after discontinuation of treatment (low-quality evidence). Compared with tricylic drugs: An enuresis alarm is more effective than tricyclic drugs at reducing relapse rates after treatment has ended (moderate-quality evidence). Compared with dry bed training: An enuresis alarm is more effective than dry bed training at reducing relapse rates at the end of treatment (moderate-quality evidence). Plus tricyclic drugs compared with alarm alone: An enuresis alarm plus tricylic drugs (imipramine, nortriptyline) seems to be less effective than an enuresis alarm alone at reducing relapse rates at six months (very low-quality evidence). Plus dry bed training compared with no treatment: An enuresis alarm plus dry bed training is no more effective at reducing relapse rates at the end of treatment compared with no treatment (moderate-quality evidence). Plus dry bed training compared with enuresis alarm alone: An enuresis alarm plus dry bed training is no more effective than an enuresis alarm alone at reducing relapse rates after treatment is discontinued (moderate-quality evidence). Plus desmopressin compared with enuresis alarm alone: We don’t know whether an enuresis alarm plus desmopressin may be more effective than an enuresis alarm alone at reducing relapse rates (very low-quality evidence).

Benefits

Enuresis alarm versus no treatment:

We found one systematic review (search date 2004, 17 RCTs). It found that enuresis alarms significantly reduced the number of wet nights (number of wet nights, 4 RCTs: WMD –3.34, 95% CI –4.14 to –2.55) compared with control, and increased treatment success rate (14 consecutive dry nights; 13 RCTs: 66% with enuresis alarm v 4% with placebo; RR for failure 0.38, 95% CI 0.33 to 0.45) during treatment lasting 10–20 weeks. The review found that, compared with placebo, enuresis alarm reduced numbers whose treatment failed or who relapsed after treatment ended (RR for failure or relapse after end of treatment, 5 RCTs: 0.56, 95% CI 0.46 to 0.68) (see table 1 ).

Enuresis alarm versus dry bed training:

See benefits of dry bed training.

Enuresis alarm versus enuresis alarm plus dry bed training:

See benefits of dry bed training.

Enuresis alarm versus desmopressin:

See benefits of desmopressin.

Enuresis alarm versus enuresis alarm plus desmopressin:

See benefits of desmopressin.

Enuresis alarm versus tricyclic drugs:

We found one systematic review which compared tricyclic drugs versus enuresis alarm (search date 2004, 7 RCTs). It found that use of an alarm significantly increased treatment success compared with imipramine after 8–14 weeks (3 RCTs; RR 0.73, 95% CI 0.61 to 0.88; see comment below). One small RCT included in the review found that use of an alarm reduced failure and relapse rates after treatment had ended (24 children; RR 0.58, 95% CI 0.36 to 0.94).

Enuresis alarm plus tricyclic drugs versus alarm:

We found one systematic review (search date 2004, 2 RCTs, 94 children) and one subsequent RCT which compared use of an enuresis alarm plus tricyclic drugs versus alarm alone. One RCT included in the review compared enuresis alarm plus nortriptyline versus alarm alone. It found no evidence that addition of tricyclic drugs to alarms increased treatment success after 5–6 weeks or reduced relapse rates compared with alarms alone (40 children; RR for failure during treatment 0.80, 95% CI 0.62 to 1.03; RR for failure or relapse 1.50, 95% CI 0.71 to 3.16).The subsequent RCT compared three treatments: enuresis alarm alone, alarm plus desmopressin, and alarm plus imipramine. It found no significant difference in the change in frequency of wet nights with imipramine plus alarm compared with alarm alone over 6 months (3-arm RCT, 105 children with monosymptomatic, primary nocturnal enuresis; mean reduction in nights per 2 weeks with enuresis: 7.4 with imipramine plus alarm v 6.9 with alarm alone; difference reported as not significant, P value not reported). After 6 months, there was no significant difference in improvement in enuresis frequency with imipramine plus alarm compared with alarm alone (improvement defined as at least 50% reduction in enuretic nights; AR for improvement: 26/33 [79%] with imipramine plus alarm v 22/37 [59%] with alarm alone; P = 0.082). After 6 months, a higher proportion of children had one or less enuretic nights per 2 weeks with alarm alone than with alarm plus imipramine; however, the significance of this difference was not reported (AR: 7/33 [21%] with imipramine plus alarm v 11/37 [30%] with alarm alone; significance assessment not performed). Treatment was discontinued in children who achieved one or less enuretic nights per 2 weeks. There was a higher rate of relapse after discontinuation of treatment in those who had received imipramine plus alarm compared with alarm alone (relapse defined as more than 2 nights per 2 weeks with enuresis; AR for relapse: 43% with imipramine plus alarm v 0% with alarm alone; significance assessment not performed).

Harms

The systematic review found that adverse effects of alarms included alarm failure, false alarms, fright, failure to wake the child, disruption by waking other family members, and non-compliance because of difficulty using the alarm.

Enuresis alarm plus tricyclic drugs versus alarm:

The subsequent RCT gave no information on adverse effects.

Comment

Enuresis alarm versus tricyclic drugs:

The pooled analysis of three RCTs comparing alarms versus imipramine included two studies which used alarms delivering an electric shock triggered by wetting. This method was felt to be unacceptable to children and their parents and is no longer recommended.

Substantive changes

No new evidence

2007; 2007: 0305.
Published online 2007 October 1.

Tricyclic drugs (imipramine, desipramine)

Summary

REDUCTION OF ENURESIS Compared with placebo: The tricylcic drugs imipramine and desipramine are more effective than placebo at reducing the number of wet nights and at achieving 14 consecutive dry nights ( high-quality evidence ). Compared with desmopressin: We don't know whether the tricyclic drugs amitriptyline and imipramine are more effective than desmopressin at reducing wet nights ( low-quality evidence ). Plus anticholinergics compared with placebo: The tricyclic drug imipramine plus the anticholinergic oxybutynin is more effective than placebo at reducing wet nights (high-quality evidence). Compared with enuresis alarm: Tricyclics are less effective than an enuresis alarm at achieving 14 consecutive dry nights at 8–14 weeks (high-quality evidence). Plus enuresis alarm compared with alarm alone: The tricylic drug imipramine plus an enuresis alarm may be no more effective than an enuresis alarm alone at reducing wet nights at 6 months (low-quality evidence). RELAPSE RATE Compared with placebo: The tricylic drug imipramine is no more effective than placebo at reducing relapse rates after treatment has ended (high-quality evidence). Compared with enuresis alarm: Tricyclics are less effective than an enuresis alarm at reducing relapse rates after treatment has ended ( moderate-quality evidence ). Plus enuresis alarm compared with alarm alone: Tricyclic drugs (imipramine, nortriptyline) plus an enuresis alarm seem to be less effective than an enuresis alarm alone at reducing relapse rates at 6 months ( very low-quality evidence ). ADVERSE EFFECTS Tricyclic drugs are associated with adverse effects such as anorexia, anxiety, constipation, depression, diarrhoea, dizziness, drowsiness, dry mouth, headache, irritability, lethargy, sleep disturbance, upset stomach, and vomiting.

Benefits

Tricyclic drugs versus placebo:

We found one systematic review (search date 2005, 4 RCTs), which found that imipramine reduced the number of wet nights during treatment compared with placebo (4 RCTs, 443 children; WMD in wet nights –1.19, 95% CI –1.56 to –0.82). It found that imipramine increased treatment success compared with placebo (10 RCTs, 627 children, RR for failure 0.77, 95% CI 0.72 to 0.83) (see table 1 ). The review found no significant difference in treatment effect or in numbers relapsing after treatment had discontinued (4 RCTs, 392 children, RR 0.98, 95% CI 0.95 to 1.03). One RCT (109 children) included in the review found that desipramine significantly increased success rate compared with placebo during 60 days of treatment (RR for failure 0.83, 95% CI 0.70 to 0.97) (see table 1 ).

Tricyclic drugs versus enuresis alarm:

See benefits of enuresis alarms.

Tricyclic drugs plus alarm versus alarm:

See benefits of enuresis alarms.

Tricyclic drugs versus desmopressin:

See benefits of desmopressin.

Tricyclic drugs plus anticholinergic drugs versus placebo:

We found one systematic review (search date 2005, 1 RCT). The RCT included in the review found that imipramine plus oxybutynin increased success rates during treatment compared with placebo (RR of failure 0.43, 95% CI 0.23 to 0.78).

Harms

The review reported that tricyclic drugs increased adverse effects compared with placebo.Effects included anorexia, anxiety, burning sensation, constipation, depression, diarrhoea, dizziness, drowsiness, dry mouth, headache, irritability, lethargy, sleep disturbance, upset stomach, and vomiting.A second review cited an adverse event rate of 34/100 in children treated with imipramine alone.Tricyclic drugs have been reported as being fatal in overdose.

Comment

None.

Substantive changes

No new evidence

2007; 2007: 0305.
Published online 2007 October 1.

Anticholinergic drugs (oxybutynin, tolterodine, hyoscyamine)

Summary

REDUCTION OF ENURESIS Compared with placebo: The anticholinergic oxybutynin is no more effective than placebo at reducing wet nights ( moderate-quality evidence ). Plus tricyclics compared with placebo: The anticholinergic oxybutynin plus the tricyclic imipramine is more effectivethan placebo at reducing wet nights ( high-quality evidence ). NOTE We found no direct information about the anticholinergic drugs oxybutynin, tolterodine, and hyoscyamine, or clinically important results comparing these drugs with desmopressin, tricycylic drugs, alarms, or dry bed training in children with nocturnal enuresis.

Benefits

Anticholinergic drugs versus placebo:

We found one systematic review (search date 2005, 1 RCT, 30 children, crossover design). The RCT included in the review found no significant difference in number of wet nights with oxybutynin compared with placebo, and the review concluded that the RCT was too small to draw conclusions.

Anticholinergic drugs plus desmopressin:

We found no systematic review or RCTs.

Anticholinergic drugs plus tricyclic drugs:

See benefits of tricyclic drugs.

Anticholinergic drugs versus other treatments:

We found no systematic review or RCTs comparing anticholinergic drugs versus desmopressin, tricyclic drugs, enuresis alarm, or dry bed training.

Harms

The review reported adverse effects after treatment with oxybutynin which included dizziness, dry mouth, headache, upset stomach, visual disturbances, digestive disturbances, nausea, vertigo, and tachycardia.

Comment

One study found that desmopressin is less effective in children with reduced functional bladder capacity, suggesting potential benefit from a combination of desmopressin plus anticholinergics in children who do not respond to single-drug therapy.

Substantive changes

No new evidence

2007; 2007: 0305.
Published online 2007 October 1.

Acupuncture

Summary

REDUCTION OF ENURESIS Compared with sham acupuncture: Laser acupuncture may be more effective than sham acupuncture at increasing treatment success rates, and at 14 consecutive dry nights after treatment has stopped ( very low-quality evidence ). Compared with desmopressin: Laser acupuncture may be no more effective than desmopressin at reducing wet nights at 6 months ( low-quality evidence ).

Benefits

Acupuncture versus sham acupuncture:

We found one systematic review (search date 2004) which included one RCT (111 children aged 5-15 years) which compared acupuncture versus sham acupuncture. It found that acupuncture significantly reduced the proportion of children remaining wet after the treatment stopped compared with sham acupuncture (number of children failing to achieve 14 dry nights after treatment had stopped: 26/56 [46%] with acupuncture v 38/55 [69%] with sham acupuncture, RR 0.67, 95% CI 0.48 to 0.94). The review noted that allocation in the trial was unclear, blinding was not possible, and the duration of follow-up was not reported.

Laser acupuncture versus desmopressin:

One systematic review (search date 2004) identified one RCT (40 children with primary nocturnal enuresis) which compared laser acupuncture versus intranasal desmopressin (20–40 µg for 3 months). Laser acupuncture was applied to seven predefined acupuncture areas for 30 seconds a session for 10–15 sessions. It found no significant difference in wet nights between laser acupuncture and intranasal desmopressin after 6 months (complete responders [reduced wet nights by 90%]: 65% with laser acupuncture v 75% with desmopressin; P value not reported).

Harms

The RCT comparing acupuncture and sham acupuncture did not report on adverse effects. The review reported that the RCT on laser acupuncture found no adverse effects with either laser acupuncture or intranasal desmopressin.

Comment

Laser acupuncture treatment may not be widely available.

Substantive changes

Acupuncture One systematic review including a comparison of acupuncture versus sham acupuncture added; benefits and harms data enhanced, categorisation unchanged (Unknown effectiveness).

2007; 2007: 0305.
Published online 2007 October 1.

Standard home alarm clock

Summary

REDUCTION OF ENURESIS Compared with routine waking every 2–3 hours: Standard home alarm clock set to wake the child immediately before their usual time of enuresis is more effective at achieving 14 consecutive dry nights at 3 months compared with routinely waking the child every 2–3 hours ( moderate-quality evidence ). RELAPSE RATES Compared with routine waking every 2–3 hours: Standard home alarm clock set to wake the child immediately before usual time of enuresis is no more effective at reducing relapse rates at 3–6 months after treatment has ended compared with routinely waking the child every 2–3 hours (moderate-quality evidence).

Benefits

We found no systematic review (see comment below) but found one RCT. The RCT (125 children with enuresis) assessed the effectiveness of standard home alarm clocks in improving enuresis (see table 1 ). It found that significantly more children achieved 14 consecutive dry nights after 3 months of treatment with a standard home alarm clock set to wake the child immediately before their usual time of enuresis compared with a strategy of routinely waking the child after 2–3 hours' sleep. The RCT found no significant difference between treatments in the numbers who relapsed at 3 and 6 months after treatment ended (P > 0.05 at both end points) (see table 1 ).

Harms

No adverse effects were reported in the RCT.

Comment

We found one systematic review, which included “behavioural and physical interventions” (including using a standard home alarm clock), but did not provide separate analyses for use of home alarms.

Substantive changes

No new evidence

2007; 2007: 0305.
Published online 2007 October 1.

Hypnotherapy

Summary

REDUCTION OF ENURESIS Compared with no treatment: Certain types of hypnotherapy (suggestions-without-trance) may be more effective than no treatment at reducing wet nights at 6 months ( very low-quality evidence ).

Benefits

Hypnotherapy versus no treatment:

We found one systematic review (search date 2004) which included one RCT.The small RCT (48 boys, aged between 8 and 13 years) compared three methods of hypnotherapy (trance plus suggestions [12 boys]; suggestions without trance [12 boys]; and trance alone [12 boys]); versus no treatment (12 boys). It found that during the 6 week treatment phase, a significant improvement in wet nights per week occurred in the trance-plus-suggestions group compared with the no-treatment group (P < 0.05) and in the suggestions-without-trance group compared with the no-treatment group (P < 0.001). It found no significant difference between the trance-alone group and the no-treatment group (reported as no significant difference, P value not given). It found that, six months after treatment, only the suggestions-without-trance group showed a significant difference from the no-treatment group (P < 0.05; further numerical data not reported). The method of randomisation was not described.The review noted that the sample size was small, and the baseline severity of enuresis was different between groups.

Harms

The RCT did not report on adverse effects.

Comment

None

Substantive changes

Hypnotherapy New option on hypnotherapy added to the review; hypnotherapy categorised as Unknown effectiveness.


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