Tricyclic and related drugs for nocturnal enuresis in children

  • Review
  • Intervention

Authors


Abstract

Background

Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2% of young adults.

Objectives

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

Search methods

We searched the Cochrane Incontinence Group Specialised Register of trials (searched 19 June 2007) and the reference lists of relevant articles including two previously published versions of this review.

Selection criteria

All randomised and quasi-randomised trials of tricyclics or related drugs for nocturnal enuresis in children were included in the review. Comparison interventions included placebo, other drugs, alarms, behavioural methods or complementary/miscellaneous interventions. 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

Fifty eight randomised trials met the inclusion criteria, involving 3721 children. The quality of many of the trials was poor. Most comparisons or outcomes were addressed only by single trials.

Treatment with most tricyclic drugs (such as imipramine, amitriptyline, viloxazine, nortriptyline, clomipramine and desipramine) was associated with a reduction of about one wet night per week while on treatment (e.g. imipramine compared with placebo, weighted mean difference (WMD) -0.92, 95% CI -1.38 to -0.46). The exception was mianserin, where results from one small trial did not reach statistical significance. About a fifth of the children became dry while on treatment (relative risk for failure (RR) 0.77, 95% CI 0.72 to 0.83), but this effect was not sustained after treatment stopped (e.g. imipramine (190/199, 96%) versus placebo (210/217, 97%): RR 0.98, 95% CI 0.95 to 1.03). There was not enough information to assess the relative performance of one tricyclic against another, except that imipramine was better than mianserin. The evidence comparing desmopressin with tricyclics was unreliable or conflicting, but in a Cochrane review of desmopressin, almost all the children failed or relapsed after stopping active treatment with desmopressin.

The evidence comparing tricyclics with alarms was also unreliable or conflicting during treatment. In one small trial all the children failed or relapsed after tricyclics stopped, compared with about half after alarms. This result was compatible with the results in the Cochrane review of alarm treatment, which found that about half the children remained dry after alarm treatment was finished. There was a little evidence from single trials to suggest that imipramine might be better than a simple reward system with star charts during treatment; worse than a complex intervention involving education, counselling, waking and retention control training; better than a restricted diet; and worse than hypnosis. However, these results need to be confirmed by further research.

Authors' conclusions

Although tricyclics and desmopressin are effective in reducing the number of wet nights while taking the drugs, most children relapse after stopping active treatment. In contrast, only half the children relapse after alarm treatment. Parents should be warned of the potentially serious adverse effects of tricyclic overdose when choosing treatment. Further research is needed into comparisons between drug and behavioural or complementary treatments, and should include relapse rates after treatment is finished.

摘要

背景

三環抗憂鬱藥及相關藥物用於兒童夜間遺尿

遺尿是一種干擾社交及令人備受壓力的症狀,影響到15∼20%五歲前的兒童及2%的年輕成人。

目標

評估三環抗憂鬱藥及相關藥物對夜間遺尿兒童的療效,以及與其他療法相比較。

搜尋策略

我們搜尋Cochrane Incontinence Group Specialised Register of trials(搜尋日期為2007年6月19日)及相關論文的參考文獻列表,包括本評論最近兩個版本。

選擇標準

所有以三環抗憂鬱藥及相關藥物治療兒童夜間遺尿之隨機或半隨機試驗均包含於本評論中。比較的介入方法包括安慰劑、其他藥物、警示、行為療法或互補性/其他方法。只聚焦於日間遺尿的試驗則予以排除。

資料收集與分析

兩位評論者獨立地評估被選出的研究的品質及抽出數據。

主要結論

有58個隨機試驗符合納入標準,共涉及3721名兒童。其中許多試驗品質不佳。大多數的比較和結果只由單一試驗所論述。大多數三環抗憂鬱藥的治療(如imipramine、amitriptyline、viloxazine、nortriptyline、clomipramine及desipramine)在治療期間約有每週減少夜間遺尿一次。﹝如imipramine與安慰劑比較,權重平均差(WMD) −0.92,95% CI −1.38∼−0.46﹞。例外的是mianserin,這是一個小規模試驗,其結果並未達統計意義。大約五分之一的兒童在治療期間不再遺尿﹝失敗相對風險(RR)0.77,95% CI 0.72∼0.83﹞,但在停止治療後效療不再持續﹝如imipramine(190/199,96%)與安慰劑(210/217,97%)比較,RR 0.98,95% CI 0.95∼1.03﹞。除了imipramine優於mianserin之外,沒有足夠資料進行對其他各種三環抗憂鬱藥的效能相互比較。比較desmopressin與三環抗憂鬱藥的證據並不可信或存有矛盾,惟有一項Cochrane對desmopressin的評論報導,停止給予desmopressin治療後幾乎所有兒童均會復發。比較三環抗憂鬱藥與警示治療的證據亦不可信或存有矛盾。在一項小規模試驗中,所有兒童停止三環抗憂鬱藥後復發遺尿,相對地,只有一半兒童在停止警示治療後復發遺尿。這項結果與Cochrane對警示治療的評論結果相符,該評論發現大約有一半兒童在警示治療結束後能保持不再遺尿。零星的試驗提供少許證據提示imipramine可能較優於星圖(star charts)等簡單的獎勵系統,但不及包含教育、諮商、喚醒及憋尿控制訓練等複合式介入;較較優於限制飲食,但不及催眠。然而,這些結果均需要進一步的研究來確認。

作者結論

雖然三環抗憂鬱藥及desmopressin在用藥期間均有效地減少夜間遺尿次數,但在停止治療後大多數兒童會復發。相對的,只有一半兒童在停止警示治療後復發遺尿。在選擇治療時,應向父母提出有關三環抗憂鬱藥過量可引發嚴重不良事件的警告。需有進一步研究比較藥物治療與行為療法或互補性療法的效果,且須包括評估治療結束後的復發率。

翻譯人

本摘要由中國醫藥大學附設醫院李明泓翻譯

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌

總結

三環抗憂鬱藥用於兒童夜間遺尿。夜間遺尿常見於童年,會引起恥辱、壓力和不便。本評論檢視58個便用三環抗憂鬱藥的試驗,共涉及3721名兒童。三環抗憂鬱藥原用於抗憂鬱,其可能之療效是來自這類藥物的其中一種副作用(影響神經傳導至膀胱的訊息)。最常用者是imipramine,此藥可使用達三個月之久。在使用三環抗憂鬱藥治療期間,約有每週減少夜間遺尿一次,而大約五分之一的兒童在治療期間不再遺尿。然而,一旦停藥便不再有效。與另一種常用的藥物desmopressin比較,三環抗憂鬱藥較便宜但卻有較多副作用。特別被關注的是三環抗憂鬱藥過量,可引發嚴重的後果。床上警示比三環抗憂鬱藥較貴,且會煩擾家人;但有一半兒童在警示治療結束後能保持不再遺尿,而且沒有藥物的副作用。

Plain language summary

Tricyclic drugs for bedwetting in children

Night-time bedwetting is common in childhood, and can cause stigma, stress and inconvenience. The review examined 58 trials of tricyclic drugs which included 3721 children. Tricyclics are antidepressants, but probably work because of one of their side effects (affecting the messages sent to the bladder by the nerves). The one most commonly used is imipramine, which can be used for up to three months. Tricyclic drugs reduce bedwetting by about one wet night per week while being used and about a fifth of the children become dry. However, they do not work once the children stop using them. Compared with the other commonly used drug, desmopressin, tricyclics are less expensive but have more side-effects. A particular concern is tricyclic overdose, which can be serious. Bed alarms are more expensive than tricyclics and more bother to families to use but about half the children remain dry after alarm treatment has finished, and they do not have the side-effects of the drugs.

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