Intervention Review

Anticholinergics for symptomatic management of Parkinson´s disease

  1. Regina Katzenschlager1,*,
  2. Cristina Sampaio2,
  3. João Costa2,
  4. Andrew Lees3

Editorial Group: Cochrane Movement Disorders Group

Published Online: 22 JUL 2002

Assessed as up-to-date: 4 MAY 2002

DOI: 10.1002/14651858.CD003735

How to Cite

Katzenschlager R, Sampaio C, Costa J, Lees A. Anticholinergics for symptomatic management of Parkinson´s disease. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD003735. DOI: 10.1002/14651858.CD003735.

Author Information

  1. 1

    Donauspital/SMZ-Ost, Department of Neurology, Vienna, Austria

  2. 2

    Faculdade de Medicina de Lisboa, Laboratório de Farmacologia Clínica e Terapêutica, Lisboa, Portugal

  3. 3

    University College London, Reta Lila Weston Institute of Neurological Studies, London, UK

*Regina Katzenschlager, Department of Neurology, Donauspital/SMZ-Ost, Langobardenstrasse, 122, Vienna, 1220, Austria. regina.katzenschlager@chello.at.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 22 JUL 2002

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Anticholinergics were the first drugs available for the symptomatic treatment of Parkinson´s disease and they are still widely used today, both as monotherapy and as part of combination regimes. They are commonly believed to be associated with a less favourable side effect profile than other antiparkinsonian drugs, in particular with respect to neuropsychiatric and cognitive adverse events. They have been claimed to exert a better effect on tremor than on other parkinsonian features.

Objectives

To determine the efficacy and tolerability of anticholinergics in the symptomatic treatment of Parkinson´s disease compared to placebo or no treatment.

Search methods

The literature search included electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966 to 2001), Old Medline (1960-1965), Index Medicus (1927 - 1959), as well as handsearching the neurology literature including the reference lists of identified articles, other reviews and book chapters.

Selection criteria

Randomised controlled trials of anticholinergic drugs versus placebo or no treatment in de-novo or advanced Parkinson´s disease, either as monotherapy or as an add-on to other antiparkinsonian drugs were included. Trials of anticholinergic drugs that were never in general clinical use were excluded.

Data collection and analysis

Data was abstracted independently by two authors. Differences were settled by discussion among all authors. Data collected included patient characteristics, disease duration and severity, concomitant medication, interventions including duration and dose of anticholinergic treatment, outcome measures, rates of and reasons for withdrawals, and neuropsychiatric and cognitive adverse events.

Main results

The initial search yielded 14 potentially eligible studies, five of which were subsequently excluded. In three cases this was because they dealt with substances that had never been marketed or had not been licensed for as far as could be traced back. One trial had been published twice in different languages. One study was excluded based on the assessment of its methodological quality.
The remaining nine studies were all of double-blind cross-over design and included 221 patients. Trial duration was between five and 20 weeks and drugs investigated were benzhexol (mean doses: 8 to 20 mg/d), orphenadrine (mean dose not reported), benztropine (mean dose not reported), bornaprine (8 to 8.25 mg/d), benapryzine (200 mg/d), and methixine (45 mg/d). Only one study involved two anticholinergic drugs. Outcome measures varied widely across studies and in many cases, the scales applied were the authors´ own and were not defined in detail. Incomplete reporting of methodology and results was frequent. The heterogeneous study designs as well as incomplete reporting precluded combined statistical analysis.
Five studies used both tremor and other parkinsonian features as outcome measures. Outcome measures in these five studies were too different for a combined analysis and results varied widely, from a significant improvement in tremor only to significant improvement in other features but not in tremor.
All studies except one (dealing with methixine) found a significant improvement from baseline on the anticholinergic drug in at least one outcome measure. The difference between placebo and active drug was reported in four studies and was found to be significant in all cases. No study failed to show superiority of the anticholinergic over placebo.
The occurrence of neuropsychiatric and cognitive adverse events was reported in all but three studies (in 35 patients on active drug versus 13 on placebo). The most frequently reported reason for drop-outs from studies was in patients on placebo due to withdrawal from pre-trial anticholinergic treatment.

Authors' conclusions

As monotherapy or as an adjunct to other antiparkinsonian drugs, anticholinergics are more effective than placebo in improving motor function in Parkinson´s disease. Neuropsychiatric and cognitive adverse events occur more frequently on anticholinergics than on placebo and are a more common reason for withdrawal than lack of efficacy.
Results regarding a potentially better effect of the anticholinergic drug on tremor than on other outcome measures are conflicting and data do not strongly support a differential clinical effect on individual parkinsonian features.
Data is insufficient to allow comparisons in efficacy or tolerability between individual anticholinergic drugs.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Anticholinergic drugs can improve movement symptoms of Parkinson's disease, but with adverse mental effects, and there is not enough evidence to compare the different drugs.

Anticholinergics were the first drugs available for Parkinson´s disease and they are still widely used. They are believed to work by counteracting an imbalance which exists in Parkinson´s disease between two chemicals in the brain which transmit messages between nerve cells. However, anticholinergic drugs have been associated with unfavourable side effects. They are used alone, or with other anti-Parkinson's drugs. The review of trials found that anticholinergics can improve movement problems in people with Parkinson's disease, but also cause adverse mental effects (such as confusion, memory problems, restlessness and hallucinations). There is not enough evidence to compare the different anticholinergic drugs.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以抗膽鹼藥物作為帕金森氏症的症狀治療

抗膽鹼藥物是第一個使用於帕金森氏症症狀治療的藥物,且至今仍被廣泛的以單一療法或合併療法的方式使用。一般認為它們比其它的帕金森氏症藥物有較少的副作用,特別在精神及認知的不良反應上。它們甚至被認為,比起治療其它的帕金森氏症症狀,在震顫的治療上有特別好的效果。

目標

和安慰劑或無治療比較,評估抗膽鹼藥物用於帕金森氏症症狀治療的療效和耐受性。

搜尋策略

我們搜尋了the Cochrane Controlled Trials Register (The Cochrane Library, 2001年,第4期)、MEDLINE (1966年到2001年)、Old Medline (1960年到1965年)、Index Medicus (1927年到1959年)等電子文獻,同時也手動搜尋神經學相關文獻,包括所有找到文章中的參考資料,其他評論及書本章節。

選擇標準

以抗膽鹼藥物和安慰劑比較或和初期或晚期帕金森氏症不治療比較的隨機對照試驗,可以是單一療法或作為其他抗帕金森氏症藥物的輔助藥物。沒有作為臨床使用的抗膽鹼藥物試驗會被我們排除。

資料收集與分析

由兩位作者分別擷取數據。意見分歧的部分經由所有作者共同討論取得共識。蒐集的數據包括病人特徵、疾病持續時間及嚴重度、併用藥物,介入包括抗膽鹼治療的持續時間和劑量、結果量測、參與者退出試驗的比率和原因,以及精神和認知上的不良反應。

主要結論

初次蒐尋找到14篇可能可用的研究,其中5篇隨後被排除。被排除的其中3篇是由於它們討論的是未上市或是還沒被核准的藥物。1個試驗已經被以不同語言發表過2次。1個研究是在評估其方法品質後被排除。剩下的9個研究都是雙盲交叉的設計,總共包含221位病患。試驗期間從5到20週都有,使用的藥物包括benzhexol (平均劑量: 8到20 mg/d)、orphenadrine (未列出平均劑量)、benztropine(未列出平均劑量)、bornaprine (8到8.25 mg/d)、benapryzine (200 mg/d)及methixine (45 mg/d)。只有1個試驗有用到2種抗膽鹼藥物。各研究和案例的結果量測差異很大,量表都是作者自行設計且沒有詳細的敘述。方法和結果經常都回報的不完整。各式各樣的研究設計及不完整的結果回報阻礙了合併的統計研究。5個研究以震顫和其它帕金森氏症症狀作為結果量測。這5個研究的結果量測差異太大以致於無法做合併分析,且結果也有很大的差異,從只有震顫有顯著改善到其他症狀有顯著改善,但震顫沒有。只有1個研究(討論methixine)有發現使用抗膽鹼藥物的組別在至少1個結果中,比一開始有顯著改善。有4個研究發現,在所有案例中,安慰劑和活性藥物有顯著的差異。沒有任何一個研究結果沒有顯示抗膽鹼藥物比安慰劑來的好。精神和認知上的不良反應,除了其中3個研究(35位病患使用活性藥物,13位使用安慰劑)外,其他都有回報。造成參與者退出試驗最常見的原因,是試驗中使用安慰劑的病患,先前使用過抗膽鹼治療。

作者結論

不管是單一療法或作為其他抗帕金森氏症藥物的輔助劑,抗膽鹼藥物在改善運動功能上比安慰劑有效。精神和認知上的不良反應,比起使用安慰劑的組別,在抗膽減藥物的組別比較常發生,而且是最常見造成退出試驗的原因,比因沒有療效而退出更常見。認為抗膽鹼藥物在治療震顫上比治療其他症狀有效的結果是有衝突的,且研究數據並沒有強烈證據支持其對於個別帕金森氏症症狀的臨床影響。目前的資料不足以去作各個抗膽鹼藥物療效或耐受性的比較。

翻譯人

本摘要由朱奕蓁翻譯。

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

總結

抗膽鹼藥物可以改善帕金森氏症的運動障礙,但有精神上的不良影響,且沒有足夠的證據去比較不同藥物。抗膽鹼藥物是第一個使用於帕金森氏症症狀治療的藥物,且至今仍被廣泛使用。一般認為它的作用是對抗帕金森氏症中,腦內2種負責神經細胞訊息傳遞的化學物質的不平衡。然而,抗膽鹼藥物常和有害的副作用有關。它們可能被單獨使用,或和其他抗帕金森藥物併用。這篇評論發現抗膽鹼藥物可以改善帕金森氏症病患的運動困難,但同時可能造成精神上的不良反應(像是困惑、記憶困難、坐立不安及幻覺)。目前沒有足夠證據能比較各種抗膽鹼藥物間的差別。