Anticholinergics for symptomatic management of Parkinson´s disease
Editorial Group: Cochrane Movement Disorders Group
Published Online: 22 JUL 2002
Assessed as up-to-date: 4 MAY 2002
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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.
- Publication Status: Edited (no change to conclusions)
- Published Online: 22 JUL 2002
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.
To determine the efficacy and tolerability of anticholinergics in the symptomatic treatment of Parkinson´s disease compared to placebo or no treatment.
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.
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.
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.
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
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.
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。
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。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。