Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease

  • Review
  • Intervention

Authors


Abstract

Background

As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase.

Objectives

To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.

Search methods

Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted.

Selection criteria

Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

Data collection and analysis

Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events.

Main results

Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration.

Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels.

Authors' conclusions

In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

摘要

背景

兒茶酚O甲基轉移脢抑制劑治療巴金森氏症使用左多巴引起的副作用

隨著巴金森氏症進行,要控制運動症狀多半需要在左多巴之外另加藥物,COMT抑制劑療法的主要目的是來增加每個左多巴劑量的有效時間因此使病人在停滯相對不動期的時間減少。

目標

在巴金森氏症病人已使用左多巴並有運動副作用的情況,比較輔助COMT抑制劑以及安慰劑的效果及安全性

搜尋策略

電子搜尋考科藍對照試驗登錄、(考科藍資料庫議題1, 2003)、MEDLINE (1966 – 2003)、EMBASE(1974 – 2003),手動搜尋灰色文獻,檢視蒐尋出的研究及文獻的參考書目,連絡COMT抑制劑的製造商

選擇標準

在臨床診斷原發性巴金森氏症的病人已使用左多巴並有長期產生副作用的情況,比較輔助COMT抑制劑以及安慰劑的隨機對照試驗

資料收集與分析

作者獨立對資料作摘要並討論資料的差異性,預後測量標準包括巴金森氏症分級分數、左多巴劑量、停滯期測量、退出治療以及副作用的頻率

主要結論

一共有14個試驗符合收錄標準,這篇回顧收錄了2566位有運動波動的巴金森氏症病人,有8個試驗在一共1560位病人上測試了entacapone及安慰劑,測試時間2到12個月不等;有6個試驗在一共1006位病人上測試了tolcapone及安慰劑,測試時間6到12個月不等。Tolcapone與entacapone皆減少了停電時間,減輕左多巴劑量以及改善運動殘疾及失能,這些是有副作用的包括增加異動症、噁心、嘔吐、腹瀉的機會,少部份服用tolcapone的病人有肝臟酵素值升高。

作者結論

在治療巴金森氏症的運動波動方面,Tolcapone與entacapone可減少停電時間,減輕左多巴劑量以及大幅改善運動殘疾及失能,這些是依據中等強度以下的證據。不過有些服用tolcapone的病人肝臟酵素值升高,加上在上市後監測期有3位產生致命的肝毒性,讓人對於tolcapone的安全性提高警覺。

翻譯人

本摘要由新光醫院吳亞縈翻譯。

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

總結

COMT抑制劑entacapone與tolcapone對於改善巴金森氏症使用左多巴造成的副作用有相似的益處,不過仍需更多關於tolcapone安全性的資訊。當巴金森氏症疾病進展,為了控制症狀常需要增加左多巴之外的藥物,COMT抑制劑主要目的是延長每個左多巴劑量的有效時間,從而讓病人處在相對無法動作的停電時間減少,Tolcapone與entacapone可減少停電時間,減輕左多巴劑量以及大幅改善運動殘疾及失能,這些是依據中等強度以下的證據。不過有些服用tolcapone的病人肝臟酵素值升高,藥物上市後監測發現有3位服用tolcapone的病人產生致命的肝毒性,結果在某些國家tolcapone已下架,在其他國家則被嚴格限制使用。

Plain language summary

The COMT inhibitors entacapone and tolcapone show similar benefits in relieving levodopa-induced complications in Parkinson's disease but more data on the safety of tolcapone is required.

As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. Tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. Post-marketing surveillance identified three cases of fatal hepatic toxicity in patients treated with tolcapone. As a result, tolcapone has been withdrawn from some countries and severe restrictions on its use have been imposed in others.

Laički sažetak

Lijekovi entakapon i tolkapon pokazuju slične korisne učinke za ublažavanje komplikacija izazvanih levodopom kod Parkinsonove bolesti, ali je potrebno više podataka o sigurnosti tolkapona

Napredovanjem Parkinsonove bolesti kontrola simptoma često zahtjeva dodatak drugih lijekova uz levodopu. Načelni cilj davanja lijekova koji su inhibitori katehol-o-metiltransferaze (KOMT) je povećati trajanje učinka svake doze levodope i na taj način smanjiti vrijeme koje pacijenti provedu u relativno nepokretnoj "off" fazi. Tolkapon i entakapon se mogu koristiti za smanjenje "off" vremena, smanjenje doze levodope i skromno poboljšanje motorike i invalidnosti. Navedeno se temelji na dokazima iz istraživanja srednje duljine trajanja. Međutim, kod nekih sudionika istraživanja koji su primali tolkapon povećana je razina jetrenih enzima. Nadzor lijeka nakon uvođenja na tržište utvrdio je tri slučaja smrtonosne toksičnosti jetre kod bolesnika liječenih tolkaponom. Zbog toga je tolkapon povučen iz nekih zemalja, a u drugima su nametnuta stroga ograničenja vezana za njegovu uporabu.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Diana Rubić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr