Serotonin and noradrenaline reuptake inhibitors (SNRI) for stress urinary incontinence in adults

 

Abstract

Background

To date, standard recommendations for the management of stress urinary incontinence (SUI) would be either pelvic floor muscle training (PFMT) or surgery. A new form of drug treatment with a serotonin-noradrenaline reuptake inhibitor (SNRI), duloxetine, may now have a place in treatment of this condition.

Objectives

To determine whether a SNRI is better than placebo (or no treatment, other pharmacological and non-pharmacological therapies, or surgery) in the treatment of women with SUI, or mixed urinary incontinence that includes stress incontinence (MUI), or both and which doses should be used.

Search methods

We searched the Cochrane Incontinence Group Specialised Register (searched 5th March 2007), CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE (January 1966 to January 2007), MEDLINE In-Process & Other Non-Indexed Citations (7 February 2007) and the reference lists of relevant articles.

Selection criteria

All randomised or quasi-randomised controlled trials of treatment for SUI or MUI, in which at least one management arm involved a SNRI.

Data collection and analysis

Two authors evaluated the trials for appropriateness for inclusion and methodological quality. Three authors performed the data extraction using predetermined criteria. Analyses were performed using the Cochrane Review Manager software, RevMan.

Main results

Ten randomised trials were included, involving 3944 adults with predominantly SUI, randomised to receive duloxetine or placebo and/ or PFMT. All arms in individual trials were comparable for various baseline characteristics. Treatment duration was between three weeks and 12 weeks.

Duloxetine was significantly better than placebo in terms of improving patients' quality of life (weighted mean difference 5.26, 95% confidence interval 3.84 to 6.68. P less than 0.00001) and perception of improvement. Individual studies demonstrated a significant reduction in the Incontinence Episode Frequency (IEF) by approximately 50% during treatment with duloxetine. With regard to objective cure, however, meta-analysis of stress pad test and 24 hour pad weight change failed to demonstrate a benefit for duloxetine over placebo though data were relatively few. Subjective cure favoured duloxetine, albeit with a small effect size (3%). One trial suggested that duloxetine was better than pelvic floor muscle training alone in reducing IEF (P less than 0.05) based on median percentage decrease in IEF per week. Although significant side effects were commonly associated with duloxetine, they were reported as acceptable.

Authors' conclusions

The available evidence suggests that duloxetine treatment can significantly improve the quality of life of patients with stress urinary incontinence, but it is unclear whether or not benefits are sustainable. Adverse effects are common but not serious. About one in three participants allocated duloxetine reported adverse effects (most commonly nausea) related to treatment, and about one in eight allocated duloxetine stopped treatment as a consequence.

 

Plain language summary

Duloxetine can improve the quality of life of patients with stress urinary incontinence, long-term effects of the treatment are unclear.

Stress urinary incontinence is involuntary urine leakage on coughing or exertion. The trials reviewed compared duloxetine against dummy placebo tablets and also pelvic floor muscle training in women with predominantly stress urinary incontinence. Duloxetine reduced the frequency of episodes of incontinence and improved quality of life scores. However, it had little impact on the numbers cured and commonly had side effects, especially nausea. More studies comparing a serotonin and noradrenaline reuptake inhibitor with placebo and surgery are required, especially if conducted independently of pharmaceutical companies.

 

摘要

背景

血清素和正腎上腺素再吸收抑制劑(SNRI)對成人應力性尿失禁的療效

至今為止，對於應力性尿失禁的標準建議仍是骨盆肌肉訓練或是手術治療，而目前一種新的藥物治療血清素與正腎上腺素在吸收抑制劑(SNRI)，duloxetine千憂解，在治療此方面的問題扮演了重要角色。

目標

決定SNRI在治療應力性尿失禁或混合性尿失禁的患者，是否優於其他對照組(無治療、其他藥物治療或手術治療)及適合的藥物劑量。

搜尋策略

搜尋的資料庫包括Cochrane Incontinence Group Specialised Register(至2007年3月5日)，MEDLINE(1966年1月至2005年8月)，CENTRAL(2006年Cochrane Library, Issue 4)，MEDLINE(1996年1月至2007年1月)，MEDLINE InProcess & Other NonIndexed Citations(至2007年2月7日)及相關文章。

選擇標準

所有關於應力性尿失禁及混合性尿失禁治療的隨機控制和準隨機控制研究，其中至少包含SNRI的使用。

資料收集與分析

二位學者評估研究篩選條件是否合宜，以及研究方法的品質。三位學者以預先設立的條件彙整資料。資料的分析處理是使用Cochrane Review Manager software, RevMan。

主要結論

10個隨機研究被篩選出來，包含3944位以應力性尿失禁表現的成人，隨機選取以duloxetine(千憂解)或安慰劑及/或骨盆肌肉訓練。個別的研究在不同的基準上仍是可互相比較的。治療的期間介於3至12周，在改善病人的生活品質上及自覺症狀的改善，Duloxetine優於控制組且具有統計上的意義。在不同的研究均顯示在有以duloxetine治療組別在失禁發生的頻率上有減少50%。就客觀的統合分析，雖然資料相對較少但證據無法顯示duloxetine較控制組具有優勢。(以stress pad test及24小時護墊重評估)而主觀感受來說，duloxetine確有其療效，及即便影響的族群約3%，其中一個研究則顯示duloxetine在改善尿失禁頻率上優於骨盆肌肉訓練(且有統計上意義)，雖然duloxetine相關副作用也不少，但大致上均是可被接受的。

作者結論

目前的證據傾向duloxetine在改善應力性尿失禁的生活品質上有所助益，但無法證實在客觀評估下有是否足夠證據支持。而duloxetine的副作用雖常見但不嚴重，以duloxetine治療的患者約1/3出現副作用，以噁心最為常見，而約1/8因副作用而停止治療。

翻譯人

本摘要由中國醫藥大學附設醫院張維君翻譯。

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

總結

Duloxetine可改善應力性尿失禁的生活品質，但目前長期的影響仍不清楚。應力性尿失禁常出現咳嗽或用力時尿失禁。這篇統整了以duloxetine及骨盆肌肉訓練及/或安慰劑治療應力性尿失禁的效果。Duloxetine減少了失禁頻率及生活品質。但影響的族群偏少且副作用常見特別是噁心，更多比較SNRI及安慰劑或手術治療是需要的，且應由不同的藥廠來主導。