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Anticholinergics for urinary symptoms in multiple sclerosis

  • Review
  • Intervention

Authors


Abstract

Background

Multiple Sclerosis (MS) is the commonest physically disabling chronic neurological disease affecting young people. Urinary symptoms are present in about 68% of people with MS but their basis has a number of potential aetiologies that can change with time.

Objectives

To assess the absolute and comparative efficacy, tolerability and safety of anticholinergic agents in MS patients.

Search methods

We searched the Cochrane Multiple Sclerosis Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue1), MEDLINE (January 1966 to January 2008), EMBASE (January 1974 to January 2008), supplemented with search of reference lists, personal communication with authors and relevant drug manufacturers.

Selection criteria

Randomised trials and cross-over trials (blinded and unblinded) that are either placebo-controlled or comparing two or more treatments.

Data collection and analysis

All four review authors independently assessed eligibility and trial quality, and extracted data. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions.

Main results

Our search strategy identified 33 articles of which thirty were excluded. Three single centre trials were included. No details were given regarding randomisation and blinding in the first two trials but side effects were frequent with all treatments.

The first (Hebjorn 1977) was a double blind randomised crossover trial. Thirty four persons with MS received three drugs Methantheline Bromide, Flavoxate Chloride and Meladrazine Tartrate each for 14 days, washout periods were not mentioned. Median volume measurements at the first bladder contraction were statistically significant at a 5% level for Methantheline Bromide only compared to no treatment.

The second (Gajewski 1986) was a prospective parallel group randomised study. Thirty four persons with MS were treated for 6-8 weeks with Oxybutynin (19 subjects) or Propantheline (15 subjects). For frequency, nocturia, urgency, and urge incontinence differences in symptom grade in favour of Oxybutynin were found. However, only for frequency the difference was statistically significant at 5% level.

The third (Fader 2007) was a double blind crossover trial. Sixty four persons with MS received oral Oxybutynin or intravesical Atropine for 14 days. Details of randomisation and blinding were given. There was no significant difference between the two treatments in any efficacy outcome measure. Side effects and QOL scores showed significant differences in favour of atropine.

Authors' conclusions

From the available evidence we cannot advocate the use of anticholinergics in MS.

摘要

背景

抗膽鹼藥物用於治療多發性硬化症之泌尿症狀

多發性硬化症是造成年輕族群身體失能最常見的慢性神經系統疾病,其中約有68%的病人會出現泌尿症狀。造成此方面症狀的幾個潛在原因會隨著時間改變。

目標

評估多發性硬化症病人使用抗膽鹼藥物的療效,耐受性和安全性。

搜尋策略

搜尋的範圍包括:Cochrane Multiple Sclerosis Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue1), MEDLINE (January 1966 to January 2008), EMBASE (January 1974 to January 2008),另外包含文章後面所附的參考資料,和作者的討論,以及相關的藥物資訊。

選擇標準

和安慰劑或是其他治療方式所作的隨機和交叉試驗(蒙蔽和非蒙蔽皆可)

資料收集與分析

四個作者分別評估文章的可用性,試驗品質以及擷取數據。數據處理依照Cochrane Handbook for Systematic Reviews of Interventions

主要結論

在這樣的搜尋條件下,總共找到了33篇文章,其中的三篇單中心試驗被納入分析。前二篇文章並沒有呈現隨機試驗和蒙蔽手法的相關細節,但是治療發生的副作用有清楚提及。第一篇(Hebjorn 1977)是一個雙盲隨機交叉試驗: 總共34位受試者,接受三種藥物治療,分別是Methantheline Bromide, Flavoxate Chloride和Meladrazine Tartrate,各使用14天。沒有提及washout period。造成膀胱初次收縮容積的中位數在接受5%的Methantheline Bromide治療的組別,只和無藥物治療的組別有顯著差異。第二篇(Gajewski 1986)是準平行組隨機研究,34個病人中19位接受Oxybutynin,15位接受Propantheline治療,為期6 – 8周。頻尿,夜尿,尿急,尿失禁等症狀的嚴重程度差異顯示Oxybutynin的治療比較有效。但是只有頻尿的症狀在5%時是有顯著差異的。第三篇(Fader 2007)是雙盲交叉試驗。64個病人接受口服Oxybutynin和膀胱內灌注Atropin治療14天。隨機試驗和蒙蔽的手法細節有呈現在文章中。二種治療的療效並沒有統計上的差別。但副作用以及生活質量評分則有統計上的意義支持atropine作為更好的治療方式。

作者結論

就目前所有的證據,並無法支持對多發性硬化症病人使用抗膽鹼藥物。

翻譯人

本摘要由新光醫院王瑄翻譯。

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

總結

多發性硬化症病人常見有泌尿道症狀,這反映了此疾病有高比率侵犯脊髓。症狀可能會在疾病加重或是復發時改變,包含頻尿,尿急,尿失禁。沒有其他症狀的成年病人可能會有尿急和尿失禁等膀胱過動症。抗膽鹼藥物因其能舒張平滑肌而可用於膀胱過動症,但在本文章所回顧的幾篇文章中,並沒有足夠的證據支持在多發性硬化症的病人使用抗膽鹼藥物。並且有多於五分之一受試者因為副作用而必須停止口服藥物治療。這反映了中樞神經系統損傷的多發性硬化症病人有比較高的比率使用此種藥物會產生副作用。

Plain language summary

Anticholinergic drugs in subjects with Multiple Sclerosis (MS) and urinary symptoms.

Urinary symptoms are very common in people with multiple sclerosis, reflecting the high prevalence of damage to the spinal cord from MS. Symptoms may change with time due to either progression or MS relapses. Common symptoms include frequency, urgency and urinary incontinence.

Adults without neurological problems may experience urgency and incontinence, manifest as so called overactive bladder syndrome or an irritable bladder. While anticholinergic drugs may benefit individuals with overactive bladder syndrome due to their muscle relaxant action, in this review we did not find sufficient evidence to prove benefit from anticholinergic drugs in people with MS. This may reflect the lack of recent research on these medications in people with MS.

In the review we also noted a high rate of adverse effects with more than one in five trial participants having to withdraw from oral treatment. This may reflect a high risk of drug adverse effects in people with CNS damage from multiple sclerosis.

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