Botulinum toxin injections for adults with overactive bladder syndrome

 

Abstract

Background

Overactive bladder syndrome (OAB) is a common condition with a significant negative impact on quality of life characterised by urgency with or without urge incontinence, frequency and nocturia.  Intravesical botulinum toxin is being increasingly used to treat severe overactive bladder refractory to standard management.  An increasing body of literature is forming that supports this technique as effective, well tolerated, and safe.  This review is a substantial update of the 2007 review of the same title.

Objectives

The objective was to compare intravesical botulinum toxin with other treatments for neurogenic and idiopathic overactive bladder in adults. The hypothesis to be addressed were whether intravesical injection of botulinum toxin was better than placebo or no treatment; pharmacological and other non-pharmacological interventions; whether higher doses of botulinum toxin were better than lower doses; whether botulinum toxin in combination with other treatments was better than other treatments alone; whether one formulation of botulinum toxin is better than another; and whether one injection technique was better than another.

Search methods

We searched the Cochrane Incontinence Group Specialised Trials Register (searched 23 February 2010). The Register contains trials identified from MEDLINE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and handsearching of journals and conference proceedings. Additionally, all reference lists of selected trials and relevant review papers were searched. No limitations were placed on the searches.

Selection criteria

All randomised or quasi-randomised controlled trials of treatment for OAB in adults in which at least one management arm involved intravesical injection of botulinum toxin were included. Participants had either neurogenic OAB or idiopathic OAB with or without stress incontinence. Comparison interventions could include no intervention, placebo, lifestyle modification, bladder retraining, pharmacological treatments, surgery, bladder instillation techniques, neuromodulation, and different types, doses, and injection techniques of botulinum toxin.

Data collection and analysis

Binary outcomes were presented as relative risk and continuous outcomes by mean differences. Little data could be synthesised across studies due to differing study designs and outcome measures. Where applicable standard deviations were calculated from P values according to the formula described in section 7.7.3.3 of the Cochrane Handbook of Systematic Reviews of Interventions. Data were tabulated where possible with results taken from trial reports where this was not possible. Where multiple publications were found, the reports were treated as a single source of data.

Main results

Nineteen studies were identified that met the inclusion criteria.  Most patients in the studies had neurogenic OAB, but some included patients with idiopathic OAB.  All studies demonstrated superiority of botulinum toxin to placebo.  Lower doses of botulinum toxin (100 to 150 U) appeared to have beneficial effects, but larger doses (300 U) may have been more effective and longer lasting, but with more side effects.  Suburothelial injection had comparable efficacy to intradetrusor injection. The effect of botulinum toxin may last for a number of months and is dependent upon dose and type of toxin used. Patients receiving repeated doses do not seem to become refractory to botulinum toxin. Botulinum toxin appeared to have beneficial effects in OAB that quantitatively exceeded the effects of intravesical resiniferatoxin. Intravesical botulinum toxin appeared to be reasonably safe; however, one study was halted due to a perceived unacceptable rate of urinary retention. 

Authors' conclusions

Intravesical botulinum toxin appears to be an effective therapy for refractory OAB symptoms, but as yet little controlled trial data exist on benefits and safety compared with other interventions, or with placebo. Further robust data are required on long term outcomes, safety, and optimal dose of botulinum toxin for OAB.

 

Plain language summary

Botulinum toxin injections into the bladder for overactive bladder syndrome in adults

Injection of botulinum toxin into the bladder is being increasingly used to treat persistent overactive bladder (OAB). This is a disorder characterised by the sudden urge to pass urine with or without incontinence, a frequent need to pass urine, and waking to pass urine during the night. We explored the research relating to how effective and safe botulinum toxin injections into the bladder are, and what the best dose of botulinum toxin is, and what is the best way of injecting it into the bladder. We found that there were several comparative studies, but these involved a relatively small number of patients. There was evidence that botulinum toxin improves the symptoms of OAB. It was unclear what the best dose of botulinum toxin was. Botulinum toxin injections into the bladder appeared to give few side effects or complications, but there were no long-term follow-up studies, and there could be rare side effects that have not been discovered yet.

 

摘要

背景

肉毒桿菌毒素注射治療成人膀胱過動症

背景：膀胱過動症是一種常見的疾病,並且對生活品質有很大的負面影響. 膀胱內肉毒桿菌毒素注射已越來越常運用於頑固性膀胱過動症,並有相當多的病例報告和相關研究文獻指出此方法確有益處

目標

本回顧的目的,是比較膀胱內肉毒桿菌毒素注射與其他治療對神經性及原發性成人膀胱過動症的效果. 著重假說在於,膀胱內肉毒桿菌毒素注射療效是否優於安慰劑,無治療,或藥理性和其他非藥理性介入;高劑量肉毒桿菌毒素是否優於低劑量;其他治療方法結合肉毒桿菌毒素使用是否優於單純使用其他治療;單一配方肉毒桿菌毒素是否較佳,以及何種注射方式為優

搜尋策略

搜尋考科藍實證醫學資料庫(2005年11月22日). 該資料庫包含MEDLINE, CINAHL,考科藍中心對照研究試驗登錄(CENTRAL),手動搜尋期刊與會議記錄. 除此之外,所有試驗列出的參考文獻皆列入搜尋範圍. 搜尋條件未做限制

選擇標準

所有成人膀胱過動症治療的隨機或半隨機對照研究試驗,其治療方法至少有一項涉及膀胱內肉毒桿菌毒素注射. 參與者患有神經性或是原發性的膀胱過動症,可能伴隨壓力性尿失禁. 處置的比較包含了:無治療;安慰劑;生活型態調整;膀胱再訓練;藥物治療;手術治療;膀胱灌注法;神經調控;以及使用不同劑量,劑型,與注射方法的肉毒桿菌注射治療

資料收集與分析

以相對危險性來表示二元變項,以平均差代表連續變項. 因為不同的設計與結果評估,研究中的數據無法被合併分析. 數據依可能和不可能之結果製表列出,若是多次發表過的報告都以單一資料來源而論

主要結論

有八項研究符合以上所提的標準. 各項研究的結果均有所不同. 大多數而言,研究結果顯示在尿失禁次數,膀胱容積,最大逼尿肌壓力,以及生活品質方面,使用肉毒桿菌毒素A均優於安慰劑. 低劑量的肉毒桿菌毒素(100∼150U)便有助益,但較高劑量(300U)顯示有更好的效果. 肉毒桿菌毒素注射對膀胱過動症的改善在數量上優於膀胱內樹脂毒素注射

作者結論

膀胱內肉毒桿菌毒素注射展現了作為膀胱過動症治療的發展潛力. 然而,在和其他處置或安慰劑比較益處及安全性時,彼此的對照研究試驗數據依然太少. 執行者需注意的是,目前支持膀胱內肉毒桿菌毒素注射效用多屬非正式的病例報告;關於大量、健全的安全性數據仍不多見. 更甚者,肉毒桿菌毒素的合適劑量與效果及安全性的關係也尚未被驗證

翻譯人

本摘要由中國醫藥大學附設醫院邱劭文翻譯。

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

總結

膀胱內肉毒桿菌毒素注射治療膀胱過動症. 膀胱內肉毒桿菌毒素注射越來越常用於治療持續性膀胱過動症. 這是一種會有突然尿急,頻尿,夜尿,偶會伴隨尿失禁的失常狀態. 我們探討的研究,是關於膀胱內肉毒桿菌毒素注射的效果、安全性,及最適當的劑量. 我們發現到少數可供比較的小樣本研究中,有證據顯示肉毒桿菌毒素可以改善膀胱過動症的症狀. 至於最適當的劑量則不清楚. 膀胱內肉毒桿菌毒素注射似乎只有少數的副作用或併發症,然而並沒有長期追蹤的研究,也可能仍有些罕見副作用尚未被發現