日本夜尿症学会編：夜尿症診療ガイドライン2021、2021.
赤司俊二：長期治療解析例による初診時臨床所見スコアー化の試みと治療予後の推定. 夜尿症研究 2009：14：29-34.
Chung K Yeung, Biji Sreedhar, Jennifer D Y Sihoe, Frances K Y Sit, Joseph Lau
Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study.
BJU Int. 2006 May;97(5):1069-73. doi: 10.1111/j.1464-410X.2006.06074.x.
Abstract/Text
OBJECTIVE: To evaluate any differences in the characteristics of primary nocturnal enuresis (PNE) between younger enuretic children and adolescents.
SUBJECTS AND METHODS: In all, 21 000 questionnaires designed to determine the presence or absence of bed-wetting, diurnal incontinence, frequency of wetting, systemic illness, and family history, were sent to children aged 5-19 years from 67 kindergartens, primary schools and secondary schools randomly selected by a computer from different areas in Hong Kong. In addition, questions were asked to evaluate when and how the parents became aware that bed-wetting is a significant medical problem deserving attention in children after the age of 5 years.
RESULTS: Of the 21,000 questionnaires distributed, 16 512 (78.6%) were completed. Among the respondents, 512 children (302 boys, 210 girls) had PNE; of these, 106 (20.7%) also had daytime incontinence. There was a marked reduction in the overall prevalence of PNE with advancing age. At 5 years old, 16.1% of children had PNE (20.7% boys, 10.8% girls; at age 9 and 19 years, 3.14% and 2.2% of children had PNE, respectively. However, this reduction was significantly more apparent among those with mild enuretic symptoms (wet <3 nights/week) than in those with more frequent bed-wetting. Furthermore, younger enuretic children behaved very differently from adolescents and older patients. As age increased there was a significant tendency towards more severe enuretic symptoms. At age 5 years, 14.3% of enuretic children wet 7 nights/week, compared with 48.3% at age 19 years (P < 0.001). In addition, significantly more adolescent boys aged >10 years had daytime urinary incontinence than had enuretic children aged < or = 10 years (32% vs 14.6%, respectively, P < 0.001). Most (89%) parents only became aware that bed-wetting was a significant medical problem deserving attention through material in the mass media over the past 3-4 years.
CONCLUSIONS: The present finding suggesting that PNE spontaneously resolves with increasing age probably applies only to those with mild enuretic symptoms. There are significant differences in characteristics between younger enuretic children and older subjects. As age increases there is an increasing proportion of enuretic patients with more severe bed-wetting. Enuretic children aged >10 years and adolescents have significantly more daytime urinary symptoms and incontinence. The previously reported low prevalence of PNE in Hong Kong was probably due to parental indifference to the problem.
Shunji Akashi, Kazue Tomita
The impact of a history of childhood nocturnal enuresis on adult nocturia and urgency.
Acta Paediatr. 2014 Sep;103(9):e410-5. doi: 10.1111/apa.12694. Epub 2014 Aug 1.
Abstract/Text
AIM: This study examined the association between a childhood history of nocturnal enuresis and nocturia and urgency as an adult.
METHODS: A questionnaire was completed by 3649 parents and grandparents of children with nocturnal enuresis. The age range of the respondents was 30-89, and 54% were female. The questionnaire included the respondent's age, underlying disease, the age at which nocturnal enuresis was resolved and any current nocturia and urgency.
RESULTS: The responses enabled us to analyse the risk factors for nocturia and urgency for the total sample, the history of nocturnal eneurisis for 2555 adults aged from 30 to 79 years and the age when nocturnal enuresis resolved for 1300 adults aged from 30 to 49 years. Respondents were significantly more likely to have nocturia and urgency as adults if they had a history of nocturnal enuresis and were aged ≥12 years when their nocturnal enuresis resolved.
CONCLUSIONS: A childhood history of nocturnal enuresis, particularly nocturnal enuresis that resolved at ≥12 years old, was associated with an increased frequency of adult nocturia and urgency. The impact of previous nocturnal enuresis on adult nocturia and urgency presents a risk that is comparable to ageing and prostatic disease.
©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Tryggve Nevéus, Eliane Fonseca, Israel Franco, Akihiro Kawauchi, Larisa Kovacevic, Anka Nieuwhof-Leppink, Ann Raes, Serdar Tekgül, Stephen S Yang, Søren Rittig
Management and treatment of nocturnal enuresis-an updated standardization document from the International Children's Continence Society.
J Pediatr Urol. 2020 Feb;16(1):10-19. doi: 10.1016/j.jpurol.2019.12.020. Epub 2020 Jan 30.
Abstract/Text
BACKGROUND: Enuresis is an extremely common condition, which, although somatically benign, poses long-term psychosocial risks if untreated. There are still many misconceptions regarding the proper management of these children.
AIM: A cross-professional team of experts affiliated with the International Children's Continence Society (ICCS) undertook to update the previous guidelines for the evaluation and treatment of children with enuresis.
METHODS: The document used the globally accepted ICCS terminology. Evidence-based literature served as the basis, but in areas lacking in primary evidence, expert consensus was used. Before submission, a full draft was made available to all ICCS members for additional comments.
RESULTS: The enuretic child does, in the absence of certain warning signs (i.e., voiding difficulties, excessive thirst), not need blood tests, radiology or urodynamic assessment. Active therapy is recommended from the age of 6 years. The most important comorbid conditions to take into account are psychiatric disorders, constipation, urinary tract infections and snoring or sleep apneas. Constipation and daytime incontinence, if present, should be treated. In nonmonosymptomatic enuresis, it is recommended that basic advice regarding voiding and drinking habits be provided. In monosymptomatic enuresis, or if the above strategy did not make the child dry, the first-line treatment modalities are desmopressin or the enuresis alarm. If both these therapies fail alone or in combination, anticholinergic treatment is a possible next step. If the child is unresponsive to initial therapy, antidepressant treatment may be considered by the expert. Children with concomitant sleep disordered breathing may become dry if the airway obstruction is removed.
Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Chung K Yeung, Mei Diao, Biji Sreedhar
Cortical arousal in children with severe enuresis.
N Engl J Med. 2008 May 29;358(22):2414-5. doi: 10.1056/NEJMc0706528.
Abstract/Text
M R Järvelin, L Vikeväinen-Tervonen, I Moilanen, N P Huttunen
Enuresis in seven-year-old children.
Acta Paediatr Scand. 1988 Jan;77(1):148-53. doi: 10.1111/j.1651-2227.1988.tb10614.x.
Abstract/Text
A random sample of 3,206 seven-year-old children was studied in order to examine the prevalence of enuresis and associated somatic and genetic risk factors. The overall prevalence of enuresis was 9.8% and the figures for nightwetting, daywetting and mixed day and night wetting 6.4%, 1.8% and 1.6% respectively. The prevalence was 9.5% among primary school children, 24.8% among children whose entry to school had been postponed and 26.6% among handicapped and mentally retarded children. If the father had been enuretic after 4 years of age the risk of the child being enuretic was 7.1 times greater than otherwise (95% confidence limits of the risk ratio 5.1-9.8, p less than 0.001), the corresponding risk ratio when the mother had been enuretic being 5.2 (3.9-7.0, p less than 0.001). Low birth-weight children were enuretic more often than children of normal birth-weight. It seems that there are at least two aetiologically significant groups of enuretic children: cases with neurological damage and mixed day and night wetting and cases with delayed maturation, with nightwetting which shows a clear sex and genetic dependency.
今村正明, 碓井智子, 上仁数義, 吉村耕治, Walid Farhat, 兼松明弘, 小川修：日本語版DVSS（Dysfunctional Voiding Symptom Score）の公式認証～小児質問票における言語学的問題を中心に～. 日本泌尿器学会雑誌 2014：105：112-121.
Maria Cederblad, Anna Sarkadi, Gunn Engvall, Tryggve Nevéus
No effect of basic bladder advice in enuresis: A randomized controlled trial.
J Pediatr Urol. 2015 Jun;11(3):153.e1-5. doi: 10.1016/j.jpurol.2015.03.004. Epub 2015 Apr 16.
Abstract/Text
BACKGROUND: There are two firstline, evidence-based treatments available for nocturnal enuresis: desmopressin and the enuresis alarm. Prior to use of these therapies, international experts usually recommend that the children also be given basic bladder training during the daytime. The rationale behind this recommendation is that daytime bladder training or urotherapy, is a mainstay in the treatment of daytime incontinence caused by detrusor overactivity. Still, there is, as yet, no firm evidence that daytime bladder training is useful against nocturnal enuresis.
AIM: To explore whether basic bladder advice has any effect against nocturnal enuresis.
STUDY DESIGN: The study was prospective, randomized, and controlled. The evaluated intervention was bladder advice, given in accordance with ICCS guidelines and focused on regular voiding, sound voiding posture, and sufficient fluid intake. Forty children aged 6 years or more with previously untreated enuresis, but no daytime incontinence, were randomized (20 in each group) to receive either first basic bladder advice for 1 month and then alarm therapy (group A) or just the alarm therapy (group B). Based on power calculations, the minimum number of children required in each treatment arm was 15.
RESULTS: The basic bladder advice did not reduce the enuresis frequency in group A (p = 0.089) and the end result after alarm therapy did not differ between the two groups (p = 0.74) (see Table). Only four children in group A had a partial or full response to bladder training, and two of these children relapsed immediately during alarm therapy.
DISCUSSION: This was the first study to evaluate, in a prospective, randomized manner, the value of daytime basic bladder training as a treatment of enuresis. It was found that the treatment neither resulted in a significant reduction in the number of wet nights, nor did it improve the success of subsequent alarm therapy.
CONCLUSIONS: The recommendation that all children with enuresis be given bladder training as a firstline therapy can no longer be supported. Instead, we recommend that treatment of these children start with the enuresis alarm or desmopressin without delay.
Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
National Clinical Guideline Centre (UK)
Nocturnal Enuresis: The Management of Bedwetting in Children and Young People
Abstract/Text
This guideline aims to provide advice on the assessment and management of children and young people with bedwetting. The guidance is applicable to children and young people up to 19 years with the symptom of bedwetting. It has been common practice to define enuresis as abnormal from 5 years and only to consider children for treatment when they are 7 years. While the prevalence of symptoms decreases with age the guideline scope did not specify a younger age limit in order to consider whether there were useful interventions that might be of benefit to children previously excluded from advice and services.
C M Glazener, J H Evans
Desmopressin for nocturnal enuresis in children.
Cochrane Database Syst Rev. 2002;(3):CD002112. doi: 10.1002/14651858.CD002112.
Abstract/Text
BACKGROUND: Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults.
OBJECTIVES: To assess the effects of desmopressin on nocturnal enuresis in children, and to compare desmopressin with other interventions.
SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register. Date of the most recent search: March 2002. The reference list of a previous version of this review was also searched.
SELECTION CRITERIA: All randomised trials of desmopressin for nocturnal enuresis in children were included in the review. Comparison interventions included placebo, other drugs, alarms or behavioural methods. Trials focused solely on daytime wetting were excluded.
DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data.
MAIN RESULTS: Forty one randomised trials involving 2760 children (of whom 1813 received desmopressin) met the inclusion criteria. The quality of many of the trials was poor. Desmopressin was compared with another drug in four trials, and with alarms in seven. Desmopressin was effective in reducing bedwetting in a variety of doses and forms. Each dose of desmopressin reduced bedwetting by at least one night per week during treatment compared with placebo (e.g. 20 microg: 1.34 fewer wet nights per week, 95% CI 1.11 to 1.57). Children on desmopressin were more likely to become dry (e.g. RR for failure to achieve 14 dry nights with 20 mcg 0.84, 95% CI 0.79 to 0.91). However, there was no difference after treatment was finished. There was no clear dose-related effect of desmopressin, but the evidence was limited. Data which compared oral and nasal administration were too few to be conclusive. While desmopressin was better than diclofenac or indomethacin, and comparison with tricyclic drugs (amitriptyline and imipramine) suggested that they might be as effective as desmopressin, the data were inconclusive due to small numbers. There were more side effects with the tricyclics. In one small trial, desmopressin resulted in more wet nights than alarms towards the end of treatment (WMD 1.4, 95% CI: 0.14 to 2.66) and the chance of failure or relapse after alarms was less (RR 9.17, 95% CI 1.28 to 65.90). Although there were fewer wet nights during alarm treatment supplemented by desmopressin compared with alarms alone (WMD -1.35, 95% CI -2.32 to -0.38), the data are inconclusive about whether this is reflected in lower failure (RR 0.88, 95%CI 0.52 to 1.50) or subsequent relapse rates (RR 0.58, 95% CI 0.31 to 1.10).
REVIEWER'S CONCLUSIONS: Desmopressin rapidly reduced the number of wet nights per week, but there was some evidence that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects, but that alarms may produce more sustained benefits. However, based on the available limited evidence, these conclusions can only be tentative. Children should be advised not to drink more than 240 ml (8 oz) fluid during desmopressin treatment in order to avoid the possible risk of water intoxication.
帆足英一 et al. ：薬効報告 酢酸デスモプレシン(KW-8008)の「夜間尿浸透圧低下型」夜尿症に対する臨床評価--プラセボを対照薬とした二重盲検比較試験. 小児科臨床 2003：56：965-982.
帆足英一, 日比逸郎, 前川喜平, 吉田尚, 生駒文彦, 赤司俊二, 柿沢至恕：夜尿症に対する酢酸デスモプレシン(KW-8008)の臨床評価 塩酸イミプラミンを対照薬とした二重盲検群間比較試験. 基礎と臨床 1995:29(16): 4219-4257.
Patrina Hy Caldwell, Miriam Codarini, Fiona Stewart, Deirdre Hahn, Premala Sureshkumar
Alarm interventions for nocturnal enuresis in children.
Cochrane Database Syst Rev. 2020 May 4;5(5):CD002911. doi: 10.1002/14651858.CD002911.pub3. Epub 2020 May 4.
Abstract/Text
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.
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Patrina H Y Caldwell, Premala Sureshkumar, Wicky C F Wong
Tricyclic and related drugs for nocturnal enuresis in children.
Cochrane Database Syst Rev. 2016 Jan 20;2016(1):CD002117. doi: 10.1002/14651858.CD002117.pub2. Epub 2016 Jan 20.
Abstract/Text
BACKGROUND: Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s.
OBJECTIVES: To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis.
SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (containing trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings), on 30 November 2015, and reference lists of relevant articles.
SELECTION CRITERIA: We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author.
MAIN RESULTS: Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response.
AUTHORS' CONCLUSIONS: There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.
J S Lovering, S E Tallett, J B McKendry
Oxybutynin efficacy in the treatment of primary enuresis.
Pediatrics. 1988 Jul;82(1):104-6.
Abstract/Text
The effectiveness of oxybutynin in the treatment of primary enuresis was evaluated in a double-blind study. A total of 30 children (25 boys, five girls), at least 6 years of age, with primary enuresis and no daytime incontinence or history of other urinary tract problems were selected at random from an enuresis clinic population. The study was explained to the families and they were told how to keep records of nocturnal bed-wetting episodes and side effects. The patients were treated with a 10 mg of oxybutynin at suppertime for 28 days. Before or after the treatment period, all children received an identical placebo for 4 weeks. Two-sided paired t tests were used to compare frequency of nocturnal enuresis. Frequency during the drug regimen did not differ significantly from that during the placebo study. There were no differences in findings between boys and girls or between children who had previously taken imipramine and those who had not. The study showed no evidence that oxybutynin is effective in treating primary enuresis.
Tryggve Nevéus, Kjell Tullus
Tolterodine and imipramine in refractory enuresis; a placebo-controlled crossover study.
Pediatr Nephrol. 2008 Feb;23(2):263-7. doi: 10.1007/s00467-007-0662-4. Epub 2007 Nov 15.
Abstract/Text
The anticholinergic drug tolterodine has been suggested to be useful in therapy-resistant enuresis. Imipramine has a proven efficiency in unselected enuretic patients, but due to its side-effect profile it is only indicated, if at all, in therapy-resistant cases. We therefore compared these two drugs to placebo. Twenty-seven children with enuresis resistant to the alarm and to desmopressin in monotherapy were given placebo, tolterodine 1-2 mg, and imipramine 25-50 mg at bedtime for 5 weeks each in a randomised, double-blind, crossover fashion. The number of wet nights during the last 2 weeks of each treatment period was compared. One patient became spontaneously dry at the start of the study, and one dropped out due to side effects. Among the remaining 25 children, the number of wet nights during placebo, tolterodine and imipramine treatment were 11.0 +/- 3.9, 10.4 +/- 3.9 and 7.8 +/- 5.1, respectively (p < 0.001). Imipramine was significantly better than both placebo (p = 0.001) and tolterodine (p = 0.006). Nine children experienced side effects on imipramine and one on tolterodine (p = 0.001). This is the first study on anticholinergics or imipramine in children with therapy-resistant enuresis. Tolterodine, in monotherapy, had no proven effect. Imipramine was better than placebo, but side effects were common.
Tack Lee, Hong Jin Suh, Hun Jae Lee, Ji Eun Lee
Comparison of effects of treatment of primary nocturnal enuresis with oxybutynin plus desmopressin, desmopressin alone or imipramine alone: a randomized controlled clinical trial.
J Urol. 2005 Sep;174(3):1084-7. doi: 10.1097/01.ju.0000169160.84418.15.
Abstract/Text
PURPOSE: We prospectively evaluated the efficacy of a combination of desmopressin and oxybutynin for treating children with nocturnal enuresis, compared to the single drugs imipramine and desmopressin.
MATERIALS AND METHODS: We enrolled 158 patients from 2003 to 2004. Children were randomly assigned to 1 of 3 groups and treated with desmopressin, imipramine or a combination of desmopressin plus oxybutynin. Of these patients 145 (100 boys and 45 girls, mean age 7.8 +/- 2.5 years, range 5 to 15) were followed for more than 6 months. Efficacy was measured at 1, 3 and 6 months in terms of average enuretic frequency, 5-scale response based on change in nocturnal enuretic frequency after treatment and posttreatment enuretic frequency as a percentage of pretreatment baseline frequency. The latter efficacy was classified according to daytime voiding symptoms. Statistical evaluation was performed using chi-square tests and ANOVA.
RESULTS: Of the 145 children followed 48 received combination therapy, 49 received desmopressin and 48 received imipramine. A total of 68 patients (47%) had monosymptomatic enuresis and 77 (53%) had polysymptomatic enuresis. Combination therapy produced the best and most rapid results regardless of whether the children had monosymptomatic or polysymptomatic enuresis.
CONCLUSIONS: Combination therapy with desmopressin plus oxybutynin for the treatment of pediatric nocturnal enuresis was well tolerated, and gave significantly faster and more cost-effective results than single drug therapy using either desmopressin or imipramine.
Paul F Austin, Genoa Ferguson, Yan Yan, Mary J Campigotto, Michele E Royer, Douglas E Coplen
Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial.
Pediatrics. 2008 Nov;122(5):1027-32. doi: 10.1542/peds.2007-3691.
Abstract/Text
OBJECTIVE: Desmopressin is an approved medical therapy for the treatment of monosymptomatic primary nocturnal enuresis. In cases of limited response to desmopressin, we have added anticholinergic therapy to desmopressin (combination therapy). To evaluate this treatment strategy, we examined the efficacy of combination therapy for primary nocturnal enuresis in desmopressin-nonresponders.
METHODS: Only patients with primary nocturnal enuresis refractory to the maximal dosage of desmopressin were enrolled. Children with lower urinary tract symptoms or bowel dysfunction were excluded, on the basis of a 3-day, 24-hour, frequency-volume chart and elimination record. Children continued to take desmopressin and were assigned randomly, in a double-blind manner, to receive either extended-release anticholinergic medication or placebo. Patients were reassessed after 1 month of therapy, with a 1-week nocturnal record.
RESULTS: Forty-one desmopressin-nonresponders were enrolled, and 7 patients were excluded because of noncompliance. The treatment groups were equally matched with respect to age, gender, functional bladder capacity, and number of wet nights per week. After 1 month of treatment, there was a significant reduction in the mean number of wet nights in the combination therapy group, compared with the placebo group. With a generalized estimating equation approach, there was a significant 66% decrease in the risk of a wet episode, compared with the placebo group.
CONCLUSIONS: This study represents the first prospective, placebo-controlled trial examining the effect of desmopressin in combination with long-acting, anticholinergic, bladder-relaxing therapy for monosymptomatic primary nocturnal enuresis.
Se Jin Park, Ki Soo Pai, Jun Mo Kim, Kwanjin Park, Kun Suk Kim, Sang Hoon Song, Sungchan Park, Sun-Ouck Kim, Dong Soo Ryu, Minki Baek, Sang Don Lee, Jung Won Lee, Young Jae Im, Sang Won Han, Jae Min Chung, Min Hyun Cho, Tae-Sun Ha, Won Yeol Cho, Hong Jin Suh, Korean Children's Continence and Enuresis Society
Efficacy and tolerability of anticholinergics in Korean children with overactive bladder: a multicenter retrospective study.
J Korean Med Sci. 2014 Nov;29(11):1550-4. doi: 10.3346/jkms.2014.29.11.1550. Epub 2014 Nov 4.
Abstract/Text
We investigated the efficacy and tolerability of various anticholinergics in Korean children with non-neurogenic overactive bladder (OAB). A total of 326 children (males:females= 157:169) aged under 18 yr (mean age 7.3±2.6 yr) who were diagnosed with OAB from 2008 to 2011 were retrospectively reviewed. The mean duration of OAB symptoms before anticholinergic treatment was 16.9±19.0 months. The mean duration of medication was 5.6±7.3 months. Urgency urinary incontinence episodes per week decreased from 1.9±3.1 to 0.4±1.5 times (P<0.001). The median voiding frequency during daytime was decreased from 9.2±5.4 to 6.3±4.2 times (P<0.001). According to 3-day voiding diaries, the maximum and average bladder capacity were increased from 145.5±66.9 to 196.8±80.3 mL and from 80.8±39.6 to 121.8±56.5 mL, respectively (P<0.001). On uroflowmetry, maximum flow rate was increased from 17.6±8.4 to 20.5±8.2 mL/sec (P<0.001). Adverse effects were reported in 14 (4.3%) children and six children (1.8%) discontinued medication due to adverse effects. Our results indicate that anticholinergics are effective to improve OAB symptoms and tolerability was acceptable without severe complications in children.
Farzaneh Sharifiaghdas, Sepideh Sharifiaghdas, Maryam Taheri
Primary Monosymptomatic Nocturnal Enuresis: Monotherapy vs Combination Therapy.
Urology. 2016 Jul;93:170-4. doi: 10.1016/j.urology.2016.02.013. Epub 2016 Mar 23.
Abstract/Text
OBJECTIVE: To evaluate the clinical results of monotherapy with combination therapy in treatment of primary monosymptomatic nocturnal enuresis (PMNE) in children.
PATIENTS AND METHODS: Between December 2008 and May 2013, we reviewed the records of 176 children with PMNE. The monotherapy group received 120 micrograms of desmopressin melt whereas the combination therapy group received 120 micrograms of desmopressin melt plus 1-2 mg oral tablet of tolterodine. The degree of response was evaluated at 1-3 months during the treatment and 6 months after complete cessation of treatment protocol.
RESULTS: Between 176 children, 84 and 92 patients received monotherapy and combination therapy, respectively. There were no statistical differences in gender, age, or baseline monthly frequency of PMNE between the two groups. At baseline, patients had an overall mean of 23.6 ± 5.6 wet nights per month, which decreased to 10.8 ± 5.6 and 7.3 ± 5.3 in monotherapy group and 8.9 ± 9.5 and 3.3 ± 4.9 in combination therapy group at 1 and 3 months after treatment. The rates of Complete plus Partial Response to treatment at 1 and 3 months for monotherapy and combination therapy group were 63.1% and 73.9% vs 72.5% and 93.47% (P value .12 vs .006). The relapse of PMNE 6 months after complete cessation of treatment was 16.39% and 9.09% for monotherapy vs combination therapy group.
CONCLUSION: This study supports the efficacy of combination therapy with desmopressin melt plus oral tolterodine over monotherapy with desmopressin melt in the first-line treatment of PMNE in children.
Copyright © 2016 Elsevier Inc. All rights reserved.
日本小児泌尿器科学会 幼小児排尿指導管理ワーキンググループ：幼小児の昼間尿失禁の診療とケアの手引き. 日本小児泌尿器科学会雑誌 2019: 29（1）: 3-19.
