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Meta-Analysis
. 2020 May 4;5(5):CD002911.
doi: 10.1002/14651858.CD002911.pub3.

Alarm interventions for nocturnal enuresis in children

Patrina Hy Caldwell  1   2 , Miriam Codarini  3 , Fiona Stewart  4 , Deirdre Hahn  2 , Premala Sureshkumar  5
Affiliations
Meta-Analysis

Alarm interventions for nocturnal enuresis in children

Patrina Hy Caldwell et al. Cochrane Database Syst Rev. .

Abstract

Background: Enuresis (bedwetting) affects up to 20% of five-year-olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by urination), behavioural interventions and drugs.

Objectives: To assess the effects of enuresis alarms for treating enuresis in children.

Search methods: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 25 June 2018), and reference lists of relevant articles.

Selection criteria: We included randomised or quasi-randomised trials of enuresis alarms or alarms combined with another intervention for treating nocturnal enuresis in children between 5 and 16 years old.

Data collection and analysis: Two review authors independently assessed risk of bias and extracted data.

Main results: We included 74 trials (5983 children). At treatment completion, alarms may reduce the number of wet nights a week compared to control or no treatment (mean difference (MD) -2.68, 95% confidence interval (CI) -4.59 to -0.78; 4 trials, 127 children; low-quality evidence). Low-quality evidence suggests more children may achieve complete response (14 consecutive dry nights) with alarms compared to control or no treatment (RR 7.23, 95% CI 1.40 to 37.33; 18 trials, 827 children) and that more children may remain dry post-treatment (RR 9.67, 95% CI 4.74 to 19.76; 10 trials, 366 children; low-quality evidence). At treatment completion, we are uncertain whether there is any difference between alarms and placebo drugs in the number of wet nights a week (MD -0.96, 95% CI -2.32 to 0.41; 1 trial, 47 children; very low-quality evidence). Alarms may result in more children achieving complete response than with placebo drugs (RR 1.59, 95% CI 1.16 to 2.17; 2 trials, 181 children; low-quality evidence). No trials comparing alarms to placebo reported the number of children remaining dry post-treatment. Compared with control alarms, code-word alarms probably slightly increase the number of children achieving complete response at treatment completion (RR 1.11, 95% CI 0.97 to 1.27; 1 trial, 353 children; moderate-quality evidence) but there is probably little to no difference in the number of children remaining dry post-treatment (RR 0.91, 95% CI 0.79 to 1.05; moderate-quality evidence). Very low-quality evidence means we are uncertain if there are any differences in effectiveness between the other different types of alarm. At treatment completion, alarms may reduce the number of wet nights a week compared with behavioural interventions (waking, bladder training, dry-bed training, and star chart plus rewards) (MD -0.81, 95% CI -2.01 to 0.38; low-quality evidence) and may increase the number of children achieving complete response (RR 1.77, 95% CI 0.98 to 3.19; low-quality evidence) and may slightly increase the number of children remaining dry post-treatment (RR 1.39, 95% CI 0.81 to 2.41; low-quality evidence). The evidence relating to alarms compared with desmopressin in the number of wet nights a week (MD -0.64, 95% CI -1.77 to 0.49; 4 trials, 285 children) and the number of children achieving complete response at treatment completion (RR 1.12, 95% CI 0.93 to 1.36; 12 trials, 1168 children) is low-quality, spanning possible harms and possible benefits. Alarms probably slightly increase the number of children remaining dry post-treatment compared with desmopressin (RR 1.30, 95% CI 0.92 to 1.84; 5 trials, 565 children; moderate-quality evidence). At treatment completion, we are uncertain if there is any difference between alarms and tricyclics in the number of wet nights a week, the number of children achieving complete response or the number of children remaining dry post-treatment, because the quality of evidence is very low. Due to very low-quality evidence we are uncertain about any differences in effectiveness between alarms and cognitive behavioural therapy, psychotherapy, hypnotherapy and restricted diet. Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin monotherapy (MD -0.88, 95% CI -0.38 to -1.38; 2 trials, 156 children; low-quality evidence). Alarm plus desmopressin may increase the number of children achieving complete response (RR 1.32, 95% CI 1.08 to 1.62; 5 trials, 359 children; low-quality evidence) and the number of children remaining dry post-treatment (RR 2.33, 95% CI 1.26 to 4.29; 2 trials, 161 children; low-quality evidence) compared with desmopressin alone. Alarm plus dry-bed training may increase the number of children achieving a complete response compared to dry-bed training alone (RR 3.79, 95% CI 1.85 to 7.77; 1 trial, 80 children; low-quality evidence). It is unclear if there is any difference in the number of children remaining dry post-treatment because of the wide confidence interval (RR 0.56, 95% CI 0.15 to 2.12; low-quality evidence). Due to very low-quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone. Of the 74 included trials, 17 reported one or more adverse events, nine reported no adverse events and 48 did not mention adverse events. Adverse events attributed to alarms included failure to wake the child, ringing without urination, waking others, causing discomfort, frightening the child and being too difficult to use. Adverse events of comparator interventions included nose bleeds, headaches and abdominal pain. There is probably a slight increase in adverse events between code-word alarm and standard alarm (RR 1.34, 95% CI 0.75 to 2.38; moderate-quality evidence), although we are uncertain because of the wide confidence interval. Alarms probably reduce the number of children experiencing adverse events compared with desmopressin (RR 0.38, 95% CI 0.20 to 0.71; 5 trials, 565 children; moderate-quality evidence). Very low-quality evidence means we cannot be certain whether the adverse event rate for alarms is lower than for other treatments.

Authors' conclusions: Alarm therapy may be more effective than no treatment in reducing enuresis in children. We are uncertain if alarm therapy is more effective than desmopressin but there is probably a lower risk of adverse events with alarms than with desmopressin. Despite the large number of trials included in this review, further adequately-powered trials with robust randomisation are still needed to determine the full effect of alarm therapy.

Trial registration: ClinicalTrials.gov NCT00209261 NCT00230594 NCT00240812 NCT00270621 NCT00404638 NCT01575678.

PubMed Disclaimer

Conflict of interest statement

PC: is one of the inventors of an enuresis alarm. The Children's Hospital at Westmead and the University of Sydney jointly owned the patent to that alarm but the patent has now lapsed. Commercialisation is possible but not assured. The Children's Hospital at Westmead has also received a research grant and payment for development of educational material on enuresis by a pharmaceutical company. MC: none known FS: none known DH: none known PS: none known

PC and PS are authors of one of the studies included in the review (Caldwell 2015), but did not contribute to the data extraction, data analysis and discussions about that study. This was completed by FS and DH.

Figures

1
1
PRISMA study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 Alarm versus no treatment or control, outcome: 1.2 Numbers achieving 14 dry nights.
5
5
Funnel plot of comparison: 1 Alarm versus no treatment or control, outcome: 1.3 Numbers achieving 14 dry nights post‐treatment.
6
6
Funnel plot of comparison: 5 Alarm versus desmopressin, outcome: 5.3 Numbers achieving 14 dry nights.
1.1
1.1. Analysis
Comparison 1: Alarm versus no treatment or control, Outcome 1: Mean number of wet nights a week
1.2
1.2. Analysis
Comparison 1: Alarm versus no treatment or control, Outcome 2: Numbers achieving 14 dry nights
1.3
1.3. Analysis
Comparison 1: Alarm versus no treatment or control, Outcome 3: Numbers achieving 14 dry nights post‐treatment
2.1
2.1. Analysis
Comparison 2: Alarm versus placebo drug, Outcome 1: Numbers achieving 14 dry nights
2.2
2.2. Analysis
Comparison 2: Alarm versus placebo drug, Outcome 2: Mean number of wet nights a week
2.3
2.3. Analysis
Comparison 2: Alarm versus placebo drug, Outcome 3: Numbers achieving 14 dry nights: subgroup analysis
3.1
3.1. Analysis
Comparison 3: Alarm versus other types of alarm, Outcome 1: Mean number of wet nights a week
3.2
3.2. Analysis
Comparison 3: Alarm versus other types of alarm, Outcome 2: Numbers achieving 14 dry nights at the end of treatment
3.3
3.3. Analysis
Comparison 3: Alarm versus other types of alarm, Outcome 3: Numbers achieving 14 dry nights post‐treatment
3.4
3.4. Analysis
Comparison 3: Alarm versus other types of alarm, Outcome 4: Numbers with adverse events
4.1
4.1. Analysis
Comparison 4: Alarm versus other behavioural interventions, Outcome 1: Mean number of wet nights a week
4.2
4.2. Analysis
Comparison 4: Alarm versus other behavioural interventions, Outcome 2: Numbers achieving 14 dry nights
4.3
4.3. Analysis
Comparison 4: Alarm versus other behavioural interventions, Outcome 3: Mean number of wet nights a week at follow‐up
4.4
4.4. Analysis
Comparison 4: Alarm versus other behavioural interventions, Outcome 4: Numbers achieving 14 dry nights post‐treatment
5.1
5.1. Analysis
Comparison 5: Alarm versus desmopressin, Outcome 1: Mean number of wet nights per week
5.2
5.2. Analysis
Comparison 5: Alarm versus desmopressin, Outcome 2: Mean number of wet nights a week at follow‐up
5.3
5.3. Analysis
Comparison 5: Alarm versus desmopressin, Outcome 3: Numbers achieving 14 dry nights
5.4
5.4. Analysis
Comparison 5: Alarm versus desmopressin, Outcome 4: Numbers achieving 14 dry nights post‐treatment
5.5
5.5. Analysis
Comparison 5: Alarm versus desmopressin, Outcome 5: Numbers with adverse events
6.1
6.1. Analysis
Comparison 6: Alarm versus tricyclics, Outcome 1: Mean number of wet nights a week
6.2
6.2. Analysis
Comparison 6: Alarm versus tricyclics, Outcome 2: Numbers achieving 14 dry nights
6.3
6.3. Analysis
Comparison 6: Alarm versus tricyclics, Outcome 3: Numbers achieving 14 dry nights post‐treatment
7.1
7.1. Analysis
Comparison 7: Alarm versus miscellaneous treatments, Outcome 1: Mean number of wet nights a week
7.2
7.2. Analysis
Comparison 7: Alarm versus miscellaneous treatments, Outcome 2: Numbers achieving 14 dry nights
7.3
7.3. Analysis
Comparison 7: Alarm versus miscellaneous treatments, Outcome 3: Number achieving 14 dry nights post‐treatment
8.1
8.1. Analysis
Comparison 8: Alarm + other intervention versus other intervention, Outcome 1: Mean number of wet nights a week
8.2
8.2. Analysis
Comparison 8: Alarm + other intervention versus other intervention, Outcome 2: Mean number of wet nights a week: alarm + desmopressin v desmopressin subgroup analysis
8.3
8.3. Analysis
Comparison 8: Alarm + other intervention versus other intervention, Outcome 3: Numbers achieving 14 dry nights
8.4
8.4. Analysis
Comparison 8: Alarm + other intervention versus other intervention, Outcome 4: Numbers achieving 14 dry nights: alarm + desmopressin v desmopressin subgroup analysis
8.5
8.5. Analysis
Comparison 8: Alarm + other intervention versus other intervention, Outcome 5: Mean number of wet nights a week at follow‐up
8.6
8.6. Analysis
Comparison 8: Alarm + other intervention versus other intervention, Outcome 6: Number achieving 14 dry nights post‐treatment
9.1
9.1. Analysis
Comparison 9: Alarm + other intervention versus alarm monotherapy, Outcome 1: Mean number of wet nights a week
9.2
9.2. Analysis
Comparison 9: Alarm + other intervention versus alarm monotherapy, Outcome 2: Numbers achieving 14 dry nights
9.3
9.3. Analysis
Comparison 9: Alarm + other intervention versus alarm monotherapy, Outcome 3: Mean number of wet nights a week at follow‐up
9.4
9.4. Analysis
Comparison 9: Alarm + other intervention versus alarm monotherapy, Outcome 4: Number achieving 14 dry nights post‐treatment
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Fagundes 2017 {published data only}
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Faraj 1999 {published data only}
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Leebeek 2001 {published data only}
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Ronen 1995 {published data only}
    1. Ronen T, Rahav G, Wozner Y. Self-control and enuresis. Journal of Cognitive Psychotherapy 1995;9:249-58. [EMBASE: 1996053557] [sr-incont6966]
    1. Ronen T, Wozner Y, Rahav G. Cognitive intervention in enuresis. Child & Family Behavior Therapy 1992;14(2):1-14. [sr-incont7998]
Sacks 1974 {published data only}
    1. Sacks S, De Leon G, Blackman S. Psychological changes associated with conditioning functional enuresis. Journal of Clinical Psychology 1974;30(3):271-6. - PubMed
Scholander 1968 {published data only}
    1. Scholander T. Treating enuresis nocturna by a combination of medicines and conditioning [Behandling av enuresis nocturna med betingning och medikamenter]. Lakartidningen 1968;65(46):4552-6. [sr-incont4565] [PMID: ] - PubMed
Seabrook 2005 {published data only}
    1. Seabrook JA, Gorodzinsky F, Freedman S. Treatment of primary nocturnal enuresis: a randomized clinical trial comparing hypnotherapy and alarm therapy. Paediatrics & Child Health 2005;10(10):609-10. [sr-incont32051] - PMC - PubMed
Shakiba 2001 {published data only}
    1. Shakiba M, Golshan M. Management of nocturnal enuresis using alarm device. Journal of Shahid Sadoughi University of Medical Sciences and Health Services 2001;9(3):17-20. [sr-incont45792]
Sloop 1973 {published data only}
    1. Sloop EW, Kennedy WA. Institutionalized retarded nocturnal enuretics treated by a conditioning technique. American Journal of Mental Deficiency 1973;77(6):717-21. - PubMed
Sukhai 1989# {published data only}
    1. Sukhai RN, Mol J, Harris AS. Combined therapy of enuresis alarm and desmopressin in the treatment of nocturnal enuresis. European Journal of Pediatrics 1989;148(5):465-7. - PubMed
Taylor 1975 {published data only}
    1. Taylor PD, Turner RK. A clinical trial of continuous, intermittent and overlearning 'bell and pad' treatments for nocturnal enuresis. Behaviour Research and Therapy 1975;13(4):281-93. [sr-incont1587] [PMID: ] - PubMed
Titawee 2000 {published data only}
    1. Titawee K, Samorn A, Wajjanin R. Alarm conditioning and traditional method for enuresis treatment in Thai children: randomized controlled trial. Siriraj Hospital Gazette 2000;52(1):10-22.
    1. Titawee K. Pad and Bell Compared to Traditional Method for Enuresis Treatment in Thai Children: Randomized Controlled Trial [thesis]. Bangkok, Thailand: Chulalongkorn University, 1998.
Tobias 2001 {published data only}
    1. Tobias NE, McCain GC. A comparison of two enuresis alarms. Urologic Nursing 2001;21(5):349-53. - PubMed
Tuncel 2014 {published data only}
    1. Tuncel A, Balci M, Oguz U, Aslan Y, Bilgin O, Atan A. Comparison of efficacy of desmopressin fast-melting formulation and enuretic alarm-only in the treatment of nocturnal enuresis (Abstract number UP.343). Urology 2014;84(4 Suppl 1):S273. - PubMed
Turner 1970 {published data only}
    1. Turner RK, Young GC, Rachman S. Treatment of nocturnal enuresis by conditioning techniques. Behaviour Research and Therapy 1970;8(4):367-91. [sr-incont5762] - PubMed
Tuygun 2007 {published data only}
    1. Tuygun C, Eroglu M, Bakirtas H, Gucuk A, Zengin K, Imamoglu A. Is second-line enuretic alarm therapy after unsuccessful pharmacotherapy superior to first-line therapy in the treatment of monosymptomatic nocturnal enuresis? Urologia Internationalis 2007;78(3):260-3. - PubMed
Van Hoeck 2008 {published data only}
    1. Van Hoeck K, Bael A, Hirche H, Lax H, Van Gool J, Trouet D. Increasing functional bladder capacity in monosymptomatic nocturnal enuresis? A randomized controlled trial in 149 pre-pubertal children (Abstract number 545 (P)). Pediatric Nephrology 2007;22(9):1546.
    1. Van Hoeck KJ, Bael A, Lax H, Hirche H, Bernaerts K, Vandermaelen V, et al. Improving the cure rate of alarm treatment for monosymptomatic nocturnal enuresis by increasing bladder capacity--a randomized controlled trial in children [see comment]. Journal of Urology 2008;179(3):1122-6; discussion 1126-7. - PubMed
    1. Van Hoeck KJ, Bael A, Van Dessel E, Van Renthergem D, Bernaerts K, Vandermaelen V, et al. Do holding exercises or antimuscarinics increase maximum voided volume in monosymptomatic nocturnal enuresis? A randomized controlled trial in children. Journal of Urology 2007;178(5):2132-6. - PubMed
Van Londen 1993 {published data only}
    1. Van Londen A, Van Londen-Barentsen MW, Van Son MJ, Mulder GA. Arousal training for children suffering from nocturnal enuresis: a 2 1/2 year follow-up. Behaviour Research and Therapy 1993;31(6):613-5. [sr-incont8009] - PubMed
    1. Van Londen A, Van Londen-Barentsen MW, Van Son MJ, Mulder GA. Relapse rate and subsequent parental reaction after successful treatment of children suffering from nocturnal enuresis: a 2 1/2 year follow-up of bibliotherapy. Behaviour Research and Therapy 1995;33(3):309-11. [sr-incont4208] - PubMed
Vogt 2010 {published data only}
    1. Vogt M, Lehnert T, Till H, Rolle U. Evaluation of different modes of combined therapy in children with monosymptomatic nocturnal enuresis. BJU International 2010;105(10):1456-9. - PubMed
Wagner 1982 {published data only}
    1. Wagner W, Johnson SB, Walker D, Carter R, Wittner J. A controlled comparison of two treatments for nocturnal enuresis. Journal of Pediatrics 1982;101(2):302-7. - PubMed
Wagner 1985 {published data only}
    1. Wagner WG, Matthews R. The treatment of nocturnal enuresis: a controlled comparison of two models of urine alarm. Journal of Developmental and Behavioral Pediatrics 1985;6(1):22-6. [sr-incont6599] - PubMed
Werry 1965 {published data only}
    1. Werry JS, Cohrssen J. Enuresis - an etiologic and therapeutic study. Journal of Pediatrics 1965;67(3):423-31. - PubMed
Wille 1986 {published data only}
    1. Wille S. Comparison of desmopressin and enuresis alarm for nocturnal enuresis. Archives of Disease in Childhood 1986;61(1):30-3. - PMC - PubMed
    1. Wille S. Primary nocturnal enuresis in children. Background and treatment. Scandinavian Journal of Urology and Nephrology. Supplementum 1994;156:1-48. [sr-incont4221] - PubMed
Wright 1974 {published data only}
    1. Wright L, Craig SC. A comparative study of amphetamine, ephedrine-atropine mixture, placebo and behavioral conditioning in the treatment of nocturnal enuresis. Journal - Oklahoma State Medical Association 1974;67(10):430-3. [sr-incont1602] - PubMed
Young 1972 {published data only}
    1. Young GC, Morgan RT. Overlearning in the conditioning treatment of enuresis: a long-term follow-up study. Behaviour Research and Therapy 1972;10(4):419-20. [sr-incont6635] - PubMed
    1. Young GC, Morgan RT. Overlearning in the conditioning treatment of enuresis. Behaviour Research and Therapy 1972;10(2):147-51. [sr-incont5761] - PubMed

References to studies excluded from this review

Akoglu 2006 {published data only}
    1. Akoglu E, Gorur S, Atik E, Okuyucu S, Sangun O. Effect of 1-deamino 8-D-arginine vasopressin spray on nasal cytology and mucociliary clearance in patients with nocturnal enuresis. International Journal of Pediatric Otorhinolaryngology 2006;70(11):1919-22. - PubMed
Aman 2005 {published data only}
    1. Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, et al. Acute and long-term safety and tolerability of risperidone in children with autism. Journal of Child and Adolescent Psychopharmacology 2005;15(6):869-84. - PubMed
Arai 1974 {published data only}
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Azrin 1973 {published data only}
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Bollard 1977 {published data only}
    1. Bollard RJ, Woodroffe P. The effect of parent-administered Dry-Bed training on nocturnal enuresis in children. Behaviour Research and Therapy 1977;15(2):159-65. - PubMed
Bollard 1982b {published data only}
    1. Bollard J, Nettelbeck T, Roxbee L. Dry-bed training for childhood bedwetting: a comparison of group with individually administered parent instruction. Behaviour Research and Therapy 1982;20(3):209-17. - PubMed
Burr 1980 {published data only}
    1. Burr ML, Dean BV, Merrett TG, Neale E, St Leger AS, Verrier-Jones ER. Effects of anti-mite measures on children with mite-sensitive asthma: a controlled trial. Thorax 1980;35(7):506-12. - PMC - PubMed
Butler 1990 {published data only}
    1. Butler RJ, Brewin CR, Forsythe WI. Relapse in children treated for nocturnal enuresis: prediction of response using pre-treatment variables. Behavioural Psychotherapy 1990;18:65-72.
Butler 2001 {published data only}
    1. Butler RJ, Holland P, Robinson J. Examination of the structured withdrawal program to prevent relapse of nocturnal enuresis. Journal of Urology 2001;166(6):2463-6. - PubMed
Cederblad 2015 {published data only}
    1. Cederblad M, Sarkadi A, Engvall G, Neveus T. No effect of basic bladder advice in enuresis: A randomized controlled trial. Journal of Pediatric Urology 2015;11(3):153-5. - PubMed
Collins 1973 {published data only}
    1. Collins RW. Importance of the bladder-cue buzzer contingency in the conditioning treatment for enuresis. Journal of Abnormal Psychology 1973;82(2):299-308. - PubMed
Collins 1975 {published data only}
    1. Collins RW, Plaska T. Mowrer's conditioning treatment for enuresis applied to geriatric residents of a nursing home. Behavior Therapy 1975;6(5):632-8.
Cracco 1982 {published data only}
    1. Cracco L, Facco L, Fava G. Positive reinforcement and enuresis: a controlled study. Formazione Psichiatrica 1982;2:65-8.
Crisp 1984 {published data only}
    1. Crisp AH, Sireling LI, Faizey J. Nocturnal activity and the enuresis alarm device. Postgraduate Medical Journal 1984;60(702):280-1. - PMC - PubMed
    1. Macaulay AJ, Gupta M, Crisp AH, Bhat AV. The relationship between nocturnal motility and the enuresis alarm device. Journal of Psychosomatic Research 1986;30(1):63-5. - PubMed
de Leon 1966 {published data only}
    1. De Leon G, Mandell W. A comparison of conditioning and psychotherapy in the treatment of functional enuresis. Journal of Clinical Psychology 1966;22(3):326-30. - PubMed
Eggert 2012 {published data only}
    1. Eggert P, Freischmidt S, Bismarck PV, Schulz-Jurgensen S. Differentiation of subgroups of monosymptomatic enuresis according to prepulse inhibition of the startle reflex. Acta Paediatrica 2012;101(7):e304-8. - PubMed
El‐Anany 1999 {published data only}
    1. El-Anany FG, Maghraby HA, Shaker SE, Abdel-Moneim AM. Primary nocturnal enuresis: a new approach to conditioning treatment. Urology 1999;53(2):405-8. - PubMed
Elmissiry 2013 {published data only}
    1. Elmissiry M, Abdelkarim A, Badawy H, Elsalmy S, Ali GA. Refractory enuresis in children and adolescents: how can urodynamics affect management and what is the optimum test? Journal of Pediatric Urology 2013;9(3):348-52. - PubMed
Fera 2004 {published data only}
    1. Fera P, Glashan R, Lelis MA, Gonzales SR, Nogueira MD, Almeida F, et al. Immediate outcome of DDAVP versus behavioural modification for treatment of monosymptomatic nocturnal enuresis: a prospective randomized study of 30 patients (Abstract). Neurourology and Urodynamics 2004;23(5/6):555-6.
Fera 2011 {published data only}
    1. Fera P, Lelis MA, Glashan Rde Q, Pereira SG, Bruschini H. Desmopressin versus behavioral modifications as initial treatment of primary nocturnal enuresis. Urologic Nursing 2011;31(5):286-9. - PubMed
Finley 1982 {published data only}
    1. Finley WW, Rainwater AJ, Johnson G 3rd. Effect of varying alarm schedules on acquisition and relapse parameters in the conditioning treatment of enuresis. Behaviour Research and Therapy 1982;20(1):69-80. - PubMed
Fordham 1989 {published data only}
    1. Fordham KE, Meadow SR. Controlled trial of standard pad and bell alarm against mini alarm for nocturnal enuresis. Archives of Disease in Childhood 1989;64(5):651-6. [MEDLINE: ] - PMC - PubMed
Forrester 1964 {published data only}
    1. Forrester RM, Stein Z, Susser MW. A trial of conditioning therapy in nocturnal enuresis. Developmental Medicine and Child Neurology 1964;6:158-66. [14141737] - PubMed
Forsythe 1970 {published data only}
    1. Forsythe WI, Redmond A. Enuresis and the electric alarm: study of 200 cases. British Medical Journal 1970;1(690):211-3. - PMC - PubMed
Freyman 1963 {published data only}
    1. Freyman R. Follow-up study of enuresis treated with a bell apparatus. Journal of Child Psychology and Psychiatry 1963;4:199-206. - PubMed
Ghanizadeh 2012 {published data only}
    1. Ghanizadeh A, Haghighat R. Nortriptyline for treating enuresis in ADHD-a randomized double-blind controlled clinical trial. Pediatric Nephrology 2012;27(11):2091-7. - PubMed
Gillison 1958 {published data only}
    1. Gillison TH, Skinner JL. Treatment of nocturnal enuresis by the electric alarm. British Medical Journal 1958;ii:1268-72. - PMC - PubMed
Goel 1984 {published data only}
    1. Goel KM, Thomson RB, Gibb EM, McAinsh TF. Evaluation of nine different types of enuresis alarms. Archives of Disease in Childhood 1984;59(8):748-55. - PMC - PubMed
Halliday 1987 {published data only}
    1. Halliday S, Meadow SR, Berg I. Successful management of daytime enuresis using alarm procedures: a randomly controlled trial. Archives of Disease in Childhood 1987;62(2):132-7. - PMC - PubMed
Hansen 1995 {published data only}
    1. Hansen AF, Jorgensen TM. Treatment of nocturnal enuresis with the bell-and-pad system. Scandinavian Journal of Urology and Nephrology. Supplementum 1995;173:101-2. - PubMed
Hanson 1988 {published data only}
    1. Hanson RH, Thompson T, Wieseler NA. Methodological considerations in enuresis-treatment research. A three-treatment comparison. Behavior Modification 1988;12(3):335-52. - PubMed
Hu 1995 {published data only}
    1. Hu WR, Xu LJ. SuoQuanLing Tie FuDai in treating enuresis. Shanghai Journal of Traditional Chinese Medicine (Shang Hai Zhong Yi Yao Za Zhi) 1995;41(9):26-7.
Hyams 1992 {published data only}
    1. Hyams G, McCoull K, Smith PS, Tyrer SP. Behavioural continence training in mental handicap: a 10-year follow-up study. Journal of Intellectual Disability Research 1992;36(Pt 6):551-8. - PubMed
Iester 1991 {published data only}
    1. Iester A, Marchesi A, Cohen A, Iester M, Bagnasco F, Bonelli R. Functional enuresis: pharmacological versus behavioral treatment. Childs Nervous System 1991;7(2):106-8. - PubMed
Jain 2010 {published data only}
    1. Jain CM, Gupta A. Clinical study of an ayurvedic compound (divyadi yoga) in the management of shayyamutrata (enuresis). AYU 2010;31(1):67-75. - PMC - PubMed
Juul 2011 {published data only}
    1. Juul KV, Klein BM, Sandstrom R, Erichsen L, Norgaard JP. Gender difference in antidiuretic response to desmopressin. American Journal of Physiology - Renal Physiology 2011;300(5):F1116-22. - PubMed
Kahane 1955 {published data only}
    1. Kahane M. An experimental investigation of a conditioning treatment and a preliminary study of the psychoanalytic theory of the etiology of nocturnal enuresis. American Psychologist 1955;10:369-70.
Kajiwara 2010 {published data only}
    1. Kajiwara M, Miyamoto K, Masumoto H, Oki M, Teishima J, Matsubara A. Combination treatment with solifenacin plus desmopressin for children with persistent nocturnal incontinence which lasts after obtaining complete cure of urge urinary incontinence (Abstract number 194). Neurourology and Urodynamics 2010;29(6):1083-4.
Kaplan 1988 {published data only}
    1. Kaplan SL, Breit M, Gauthier B, Busner J. A comparison of three nocturnal enuresis treatment methods. Journal of the American Academy of Child and Adolescent Psychiatry 1988;28(2):282-6. - PubMed
Kazemi 2013 {published data only}
    1. Kazemi Rashed F, Nourizade D, Hajebrahimi S, Hasanzade K, Otoofat A. Does combination therapy with desmopressin and tolterodine improve the treatment outcomes of patients with monosymptomatic nocturnal enuresis? A randomized clinical controlled trial. ISRN Urology 2013;2013:413146. - PMC - PubMed
Komissarov 1990 {published data only}
    1. Komissarov VI, Tret'iakova EE. The time-course of changes in function of the kinesthetic and acoustic analyzers in children with enuresis as influenced by acupuncture. Zhurnal Nevropatologii i Psikhiatrii Imeni S - S - Korsakova 1990;90(8):44-7. - PubMed
Kooijman 1986 {published data only}
    1. Kooijman MJ, Bosch JD. Supportive research on treatment of enuresis with a urine alarm. Nederlands Tijdschrift voor Psychology en haar Grensgebieden 1986;41(7):325-8.
Kosilov 2015 {published data only}
    1. Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV. Sensibility of children of different age groups to alarm intervention for enuresis. Journal of Nepal Paediatric Society 2015;35(1):49-56. [sr-incont70803]
Kyneb 1975 {published data only}
    1. Kyneb P, Biorn-Henriksen T. Treatment of enuresis of schoolchildren with 'waking-apparatus' [Behandling af enuresis hos skoleborn ved vaekkeapparat]. Maanedsskrift for Praktisk Laegegerning 1975;53(5):250-9.
Liu 2000 {published data only}
    1. Liu X, Zhai WS, Huang S, Huang YJ, Chen SM. Clinical observation of the treatment of infantile enuresis with suoquan capsule. Chinese Journal of Information on Traditional Chinese Medicine [Zhong Guo Zhong Yi Yao Xin Xi Za Zhi] 2000;7(6):55-6.
Lovibond 1963 {published data only}
    1. Lovibond SH. Intermittent reinforcement in behaviour therapy. Behaviour Research and Therapy 1963;1(2-4):127-32. [sr-incont11232] - PubMed
Lovibond 1964d {published data only}
    1. Lovibond SH. Field experiments on the reduction of the relapse rate. In: Conditioning and Enuresis. New York: MacMillan (Pergamon Press), 1964:121-31.
Mahler 2012 {published data only}
    1. Mahler B, Kamperis K, Schroeder M, Frokiaer J, Djurhuus JC, Rittig S. Sleep deprivation induces excess diuresis and natriuresis in healthy children. American Journal of Physiology. Renal Physiology 2012;302(2):F236-43. - PubMed
Mahony 1973 {published data only}
    1. Mahony DT, Laferte RO, Mahoney JE. Studies of enuresis. VI. Observations on sphincter-augmenting effect of imipramine in children with urinary incontinence. Urology 1973;1(4):317-23. - PubMed
McConaghy 1969 {published data only}
    1. McConaghy N. A controlled trial of imipramine, amphetamine, pad-and-bell conditioning and random awakening in the treatment of nocturnal enuresis. Medical Journal of Australia 1969;2(5):237-9. - PubMed
Merks 2012 {published data only}
    1. Merks BT, Burger H, Willemsen J, Van Gool JD, De Jong TP. Melatonin treatment in children with therapy-resistant monosymptomatic nocturnal enuresis. Journal of Pediatric Urology 2012;8(4):416-20. - PubMed
Monda 1995 {published data only}
    1. Monda JM, Husmann DA. Primary nocturnal enuresis: a comparison among observation, imipramine, desmopressin acetate and bed-wetting alarm systems. Journal of Urology 1995;154(2 Pt 2):745-8. - PubMed
Montaldo 2012 {published data only}
    1. Montaldo P, Tafuro L, Rea M, Narciso V, Iossa AC, Gado RD. Desmopressin and oxybutynin in monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial and an assessment of predictive factors. BJU International 2012;110(8 Pt B):E381-6. - PubMed
Muller 1999 {published data only}
    1. Muller D. Central nervous effect of DDAVP in children with primary nocturnal enuresis: side-effect or effect? European Journal of Pediatrics 1999;158(2):27.
NCT00209261 {published data only}
    1. NCT00209261, Drug company. A 6-week open label cross-over study with 2 different daily doses of Minirin© oral lyophilisate in children and adolescents with primary nocturnal enuresis (PNE) (PALAT) [A 6-week open label cross-over study with 2 different daily doses of Minirin® oral lyophilisate (120 micro g and 240 micro g) and 2 different daily doses of Minirin® tablet (0.2 mg and 2 x 0.2 mg) in children and adolescents with primary nocturnal enuresis (PNE)]. clinicaltrials.gov/show/NCT00209261 (first received 21 September 2005). [EUCTR2004-000593-32-DE] [NCT00209261] [sr-incont46750]
NCT00230594 {published data only}
    1. NCT00230594, Drug company. Desmopressin response in the young (DRY) [Desmopressin response in the young: a double-blind, randomised, placebo-controlled, dose-titration study with three different doses (120 mcg, 240 mcg and 360 mcg) of desmopressin administered as a new melt tablet in children and adolescents with primary nocturnal enuresis (PNE)]. clinicaltrials.gov/show/NCT00230594 (first received 3 October 2005). [NCT00230594] [sr-incont46748]
NCT00240812 {published data only}
    1. NCT00240812, Drug company. A study to determine if ibuprofen in combination with pseudoephedrine HCl is more effective than each drug alone in the treatment of nighttime bedwetting [A comparative study of coadministered doses of ibuprofen and pseudoephedrine HCl and each drug alone in the treatment of primary nocturnal enuresis in children]. clinicaltrials.gov/show/NCT00240812 (first received 18 October 2005). [NCT00240812] [sr-incont46749]
NCT00270621 {published data only}
    1. NCT00270621, McGrath PJ. Family Help Program: nighttime enuresis treatment program [Family Help Program: primary care delivery by telephone for psychological and behavioural problems (pediatric enuresis)]. clinicaltrials.gov/show/NCT00270621 (first received 28 December 2005). [NCT00270621] [sr-incont46753]
NCT00404638 {published data only}
    1. NCT00404638, Cohen HA. Treatment of enuresis nocturna by circular muscle exercise (Paula method). clinicaltrials.gov/show/NCT00404638 (first received 29 November 2006). [NCT00404638] [sr-incont46752]
NCT01078753 {published data only}
    1. NCT01078753, Drug company. Study with two different doses of desmopressin orally lyophilisate tablet with nocturnal enuresis (PNE) [A double-blind, placebo-controlled, phase III comparative study with FE992026 in children and adolescents with reduced night-time urinary osmolarity-type nocturnal enuresis]. clinicaltrials.gov/show/NCT01078753 (first received 2 March 2010). [NCT01078753] [sr-incont46747]
NCT01575678 {published data only}
    1. NCT01575678, Rittig S, Borg B. The effect of melatonin on nocturnal enuresis. clinicaltrials.gov/show/NCT01575678 (first received 11 April 2012). [EUCTR2011-004138-33] [NCT01575678] [sr-incont46751]
Osterberg 2006 {published data only}
    1. Osterberg O, Savic RM, Karlsson MO, Simonsson US, Norgaard JP, Walle JV, et al. Pharmacokinetics of desmopressin administrated as an oral lyophilisate dosage form in children with primary nocturnal enuresis and healthy adults. Journal of Clinical Pharmacology 2006;46(10):1204-11. - PubMed
Park 2010 {published data only}
    1. Park SJ, Kim JH, Shin JI. Insight on the mechanism of the effects of hydrochlorothiazide on nocturnal enuresis. Urologia Internationalis 2010;85(2):248. - PubMed
Perrin 2015 {published data only}
    1. Perrin N, Sayer L, While A. The efficacy of alarm therapy versus desmopressin therapy in the treatment of primary mono-symptomatic nocturnal enuresis: a systematic review. Primary Health Care Research and Development 2015;16(1):21-31. [sr-incont68081] - PubMed
Peterson 1969 {published data only}
    1. Peterson RA, Wright RL, Hanlon CC. The effects on extending the CS-UCS interval of the effectiveness of the conditioning treatment for nocturnal enuresis. Behaviour Research and Therapy 1969;7(4):351-7. - PubMed
Philpott 1970 {published data only}
    1. Philpott MG. The treatment of enuresis; further clinical experience with imipramine. British Journal of Clinical Practice 1970;24(8):327-9. - PubMed
Pretlow 1999 {published data only}
    1. Pretlow RA. Treatment of nocturnal enuresis with an ultrasound bladder volume controlled alarm device. Journal of Urology 1999;162(3 Pt 2):1224-8. - PubMed
Radvanska 2011 {published data only}
    1. Radvanska E, Kamperis K, Kleif A, Kovacs L, Rittig S. Effect of laser acupuncture for monosymptomatic nocturnal enuresis on bladder reservoir function and nocturnal urine output. Journal of Urology 2011;185(5):1857-62. - PubMed
Raheem 2012 {published data only}
    1. Raheem AA, Farahat Y, EL-Gamal O, Ragab M, Radwan M, El-Bahnasy AH, et al. The role of posterior tibial nerve stimulation in the treatment of refractory monosymptomatic nocturnal enuresis. A pilot study (Abstract number 260). Neurourology and Urodynamics 2012;31(6):1065-6. - PubMed
Raheem 2013 {published data only}
    1. Raheem AA, Farahat Y, EL-Gamal O, Ragab M, Radwan M, El-Bahnasy AH, et al. Role of posterior tibial nerve stimulation in the treatment of refractory monosymptomatic nocturnal enuresis: a pilot study. Journal of Urology 2013;189(4):1514-8. - PubMed
Redsell 2003 {published data only}
    1. Redsell SA, Collier J, Garrud P, Evans JH, Cawood C. Multimedia versus written information for nocturnal enuresis education: a cluster randomized controlled trial. Child: Care, Health and Development 2003;29(2):121-9. - PubMed
Said 1991 {published data only}
    1. Said JA, Wilson PH, Hensley VR. Primary versus secondary enuresis: differential response to urine-alarm treatment. Child & Family Behavior Therapy 1991;13(2):1-13. [DOI: 10.1300/J019v13n02_01] - DOI
Sanchetee 1986 {published data only}
    1. Sanchetee S, Sanchetee A, Mehta LM. A placebo-controlled study of pyrithinol (encephabol) in nocturnal enuresis. Indian Medical Gazette 1986;120(4):127-9.
Scott 1993 {published data only}
    1. Scott MA. Facilitating Pelvic Floor Conditioning in Primary Nocturnal Enuresis [doctoral thesis]. Memphis, Tennessee, USA: University of Memphis, 1993.
Shulz 1978 {published data only}
    1. Shulz D, Sureth H, Lubisch G. A comparison of two behaviour therapeutic methods in the treatment of enuresis. Zeitschrift fur Klinische Psychologie 1978;7(2):141-8.
Sireling 1983 {published data only}
    1. Sireling LI, Crisp AH. Sleep and the enuresis alarm device. Journal of the Royal Society of Medicine 1983;76(2):131-3. - PMC - PubMed
Skoog 1998 {published data only}
    1. Skoog S, Stowks A, Turner K. Oral desmopressin: a randomized double-blind placebo controlled study of effectiveness in children with primary nocturnal enuresis. Mezhdunarodnyi Meditsinskii Zhurnal 1998;4:173-8. - PubMed
Smith 1979 {published data only}
    1. Smith PS. A comparison of different methods of toilet training the mentally handicapped. Behaviour Research and Therapy 1979;17(1):33-43. - PubMed
Su 2004 {published data only}
    1. Su H. Treating 106 cases of enuresis with Yi Niao Gao navel administration. Chinese Journal of Information on Traditional Chinese Medicine [Zhong Guo Zhong Yi Yao Xin Xi Za Zhi] 2004;11(6):531.
Taghavi 2010 {published data only}
    1. Taghavi Ardakani A, Honarpisheh A, Fakharian E, Talebian A, Jamali M, Moosavi GA, et al. Oral versus nasal vasopressin in the treatment of nocturnal enuresis in 5- to 12-year-old children. Iranian Journal of Child Neurology 2010;4(1):13-6.
Tang 2010 {published data only}
    1. Tang FZ, Liu YL, Wen FQ, Zhang ZX. Comparison of therapeutic effects in severe nocturia: gradual versus immediate drug withdrawal. Zhongguo Dang Dai Er Ke za Zhi [Chinese Journal of Contemporary Pediatrics] 2010;12(3):198-200. - PubMed
Taylor 1963 {published data only}
    1. Taylor IO. A scheme for the treatment of enuresis by electric buzzer apparatus. Medical Officer 1963;110:139-340.
Van Kampen 2009 {published data only}
    1. Van Kampen M, Bogaert G, Lemkens H, Akinwuntan E. The influence of age, motivation and pelvic floor muscle exercises on the full-spectrum therapy for nocturnal enuresis: a randomized controlled trial (Abstract number 47). Neurourology and Urodynamics 2005;24(5/6):478-80.
    1. Van Kampen M, Lemkens H, Deschamps A, Bogaert G, Geraerts I. Influence of pelvic floor muscle exercises on full spectrum therapy for nocturnal enuresis. Journal of Urology 2009;182(4 Suppl):2067-71. - PubMed
Wickes 1958 {published data only}
    1. Wickes IG. Treatment of persistent enuresis with the electric buzzer. Archives of Disease in Childhood 1958;33(168):160-4. - PMC - PubMed
Wu 2007 {published data only}
    1. Wu F, Yiao MH. Clinical observation of Reyiting decoction in treatment of infant enuresis with sthenic fever due to retention of heat in the spleen and stomach. Zhongguo Zhong Yao za Zhi [China Journal of Chinese Materia Medica] 2007;32(15):1572-4.
Young 1965 {published data only}
    1. Turner RK. CNS stimulant drugs and conditioning treatment of nocturnal enuresis: a long term follow-up study. Behaviour Research and Therapy 1966;4(3):225-8. - PubMed
    1. Young GC, Turner RK. CNS stimulant drugs and conditioning treatment of nocturnal enuresis. Behaviour Research and Therapy 1965;3(2):93-101. - PubMed
Yuan 1995 {published data only}
    1. Yuan B. The treatment of enuresis in children by He-Ne laser irradiation in 32 cases. Journal of Nanjing College of Traditional Chinese Medicine [Nanjing Zhong Yi Xue Yuan Xue Bao] 1995;11(3):54-5.
Zhang 1990 {published data only}
    1. Zhang H, Huang J. Preliminary study of traditional Chinese medicine treatment of minimal brain dysfunction: analysis of 100 cases. Chung Hsi i Chieh Ho Tsa Chih - Chinese Journal of Integrated Traditional & Western Medicine 1990;10(5):278-9. - PubMed
Zivkovic 2012 {published data only}
    1. Zivkovic V, Lazovic M, Vlajkovic M, Slavkovic A, Dimitrijevic L, Stankovic I, et al. Diaphragmatic breathing exercises and pelvic floor retraining in children with dysfunctional voiding. European Journal of Physical and Rehabilitation Medicine 2012;48(3):413-21. - PubMed

References to studies awaiting assessment

Unuvar 2005 {published data only}
    1. Unuvar T, Sonmez 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. International Urology and Nephrology 2005;37(4):751-7. - PubMed

References to ongoing studies

NCT03389412 {published data only}
    1. EUCTR2017-002169-23-DK. The effect of clinical characterization of children with bedwetting on the efficacy of therapy [The effect of clinical characterization of children with monosymptomatic nocturnal enuresis on the efficacy of desmopressin and alarm therapy]. clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-00... (first received 30 June 2017). [EUCTR2017-002169-23-DK] [NCT03389412] [sr-incont77744]
    1. NCT03389412, Rittig S, Jorgensen CS, Dossche L, Wen J. The effect of selecting treatment with desmopressin or alarm to children with enuresis based on home recordings [The effect of clinical characterization of children with monosymptomatic nocturnal enuresis on the efficacy of desmopressin and alarm therapy]. clinicaltrials.gov/show/NCT03389412 (first received 3 January 2018). [EUCTR2017-002169-23-DK] [NCT03389412] [TrialID.DRYCHILD.] [sr-incont77912]

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References to other published versions of this review

Glazener 2001
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Glazener 2007
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