Deshpande Aniruddh V, Caldwell Patrina H Y, Sureshkumar Premala
Department of Surgery and Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Australia.
Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD002238. doi: 10.1002/14651858.CD002238.pub2.
Enuresis (bedwetting) is a socially stigmatising and stressful condition which affects around 15% to 20% of five-year olds and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. Drugs (including desmopressin, tricyclics and other drugs) have often been tried to treat nocturnal enuresis.
To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children and to compare them with other interventions.
We searched the Cochrane Incontinence Group Specialised Register of trials (searched 15 December 2011), which includes searches of MEDLINE and CENTRAL, to identify published and unpublished randomised and quasi-randomised trials. The reference lists of relevant articles were also searched.
All randomised trials of drugs (excluding desmopressin or tricyclics) for treating nocturnal enuresis in children up to the age of 16 years were included in the review. Trials were eligible for inclusion if children were randomised to receive drugs compared with placebo, other drugs or behavioral interventions for nocturnal enuresis. Studies which included children with daytime urinary incontinence or children with organic conditions were also included in this review if the focus of the study was on nocturnal enuresis. Trials focused solely on daytime wetting and trials of adults with nocturnal enuresis were excluded.
Two review authors independently assessed the quality of the eligible trials and extracted data. Differences between review authors were settled by discussion with a third review author.
A total of 40 randomised or quasi-randomised controlled trials (10 new in this update) met the inclusion criteria, with a total of 1780 out of 2440 children who enrolled receiving an active drug other than desmopressin or a tricyclic. In all, 31 different drugs or classes of drugs were tested. The trials were generally small or of poor methodological quality. There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus placebo, when compared to placebo indomethacin (risk ratio [RR] 0.36, 95% CI 0.16 to 0.79), diazepam (RR 0.22, 95% CI 0.11 to 0.46), mestorelone (RR 0.32, 95% CI 0.17 to 0.62) and atomoxetine (RR 0.81, 95% CI 0.70 to 0.94) appeared to reduce the number of children failing to have 14 consecutive dry nights. Although indomethacin and diclofenac were better than placebo during treatment, they were not as effective as desmopressin and there was a higher chance of adverse effects. None of the medications were effective in reducing relapse rates, although this was only reported in five placebo controlled trials.For drugs versus drugs, combination therapy with imipramine and oxybutynin was more effective than imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.94) and also had significantly lower relapse rates than imipramine monotherapy (RR 0.35, 95% CI 0.16 to 0.77). There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus behavioural therapy, bedwetting alarms were found to be better than amphetamine (RR 2.2, 95% CI 1.12 to 4.29), oxybutynin (RR 3.25, 95% CI 1.77 to 5.98), and oxybutynin plus holding exercises (RR 3.3, 95% CI 1.84 to 6.18) in reducing the number of children failing to achieve 14 consecutive dry nights.Adverse effects of drugs were seen in 19 trials while 17 trials did not adequately report the occurrence of side effects.
AUTHORS' CONCLUSIONS: There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials.
遗尿症（尿床）是一种会带来社会污名化且令人倍感压力的状况，约15%至20%的五岁儿童以及高达2%的青年成人受其影响。尽管自然缓解率较高，但对儿童造成的社会、情感和心理代价可能很大。人们经常尝试使用药物（包括去氨加压素、三环类药物及其他药物）来治疗夜间遗尿症。
评估去氨加压素和三环类药物以外的药物对儿童夜间遗尿症的疗效，并与其他干预措施进行比较。
我们检索了Cochrane尿失禁组专业试验注册库（检索日期为2011年12月15日），其中包括对MEDLINE和CENTRAL的检索，以识别已发表和未发表的随机及半随机试验。我们还检索了相关文章的参考文献列表。
本综述纳入了所有针对16岁以下儿童治疗夜间遗尿症的药物（不包括去氨加压素或三环类药物）随机试验。如果儿童被随机分配接受药物治疗，并与安慰剂、其他药物或夜间遗尿症行为干预措施进行比较，则这些试验符合纳入标准。如果研究重点是夜间遗尿症，那么纳入了患有日间尿失禁儿童或患有器质性疾病儿童的研究也包括在本综述中。仅关注日间尿床的试验以及成人夜间遗尿症试验被排除。
两位综述作者独立评估符合条件试验的质量并提取数据。综述作者之间的分歧通过与第三位综述作者讨论解决。
共有40项随机或半随机对照试验（本次更新新增10项）符合纳入标准，在纳入研究的2440名儿童中，共有1780名接受了去氨加压素或三环类药物以外的活性药物治疗。总共测试了31种不同的药物或药物类别。这些试验通常规模较小或方法学质量较差。关于停药后结局的数据总体较少。对于药物与安慰剂的比较，与安慰剂相比，吲哚美辛（风险比[RR]0.36，95%置信区间0.16至0.79）、地西泮（RR 0.22，95%置信区间0.11至0.46）、美睾酮（RR 0.32，95%置信区间0.17至0.62）和托莫西汀（RR 0.81，95%置信区间0.70至0.94）似乎减少了未能连续14个晚上保持干爽的儿童数量。尽管吲哚美辛和双氯芬酸在治疗期间优于安慰剂，但它们不如去氨加压素有效，且不良反应发生几率更高。没有一种药物在降低复发率方面有效，尽管这仅在五项安慰剂对照试验中有所报告。对于药物与药物的比较，丙咪嗪与奥昔布宁联合治疗比丙咪嗪单药治疗更有效（RR 0.68，95%置信区间0.50至0.94），且复发率也显著低于丙咪嗪单药治疗（RR 0.35，95%置信区间0.16至0.77）。关于停药后结局的数据总体较少。对于药物与行为疗法的比较，发现尿床报警器在减少未能连续14个晚上保持干爽的儿童数量方面优于苯丙胺（RR 2.2，95%置信区间1.12至4.29）、奥昔布宁（RR 3.25，95%置信区间1.77至5.98）以及奥昔布宁加憋尿训练（RR 3.3，95%置信区间1.84至6.18）。19项试验观察到了药物的不良反应，而17项试验未充分报告副作用的发生情况。
没有足够证据判断所纳入的药物单独使用时能否治愈尿床。仅有有限证据表明去氨加压素、丙咪嗪和遗尿报警器疗法比与之比较的所纳入药物更有效。在其他综述中，去氨加压素、三环类药物和报警器干预措施在治疗期间已被证明有效。也有证据表明抗胆碱能疗法联合治疗通过降低约20%的复发率提高了其他既定疗法（如丙咪嗪、去氨加压素和遗尿报警器）的疗效，尽管无法确定哪些儿童会从联合治疗中获益。未来研究应在严格且有足够效力的试验中评估联合治疗相对于既定治疗的作用。
