Methadone at tapered doses for the management of opioid withdrawal

 

Abstract

Background

Despite widespread use in many countries the evidence of tapered methadone's efficacy in managing opioid withdrawal has not been systematically evaluated.

Objectives

To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate.

Search methods

We searched: Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2008), PubMed (January 1966 to December 2007), EMBASE (January 1988 to December 2007), CINAHL (2003- December 2007), PsycINFO (January 1985 to December 2004), reference lists of articles.

Selection criteria

All randomised controlled trials which focus on the use of tapered methadone versus all other pharmacological detoxification treatments or placebo for the treatment of opiate withdrawal.

Data collection and analysis

Two reviewers assessed the included studies. Any doubt about how to rate the studies were resolved by discussion with a third reviewer. Study quality was assessed according to the criteria indicated in Cochrane Reviews Handbook 4.2.

Main results

Twenty trials involving 1907 people were included. Comparing methadone versus any other pharmacological treatment we observed no clinical difference between the two treatments in terms of completion of treatment, relative risk (RR) 1.08 (95% CI 0.95 to 1.24) and results at follow-up RR 1.17 (95% CI 0.72 to 1.92). It was impossible to pool data for the other outcomes but the results of the studies did not show significant differences between the considered treatments. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (five studies), anxiolytic (two studies). Comparing methadone with placebo (two studies) more severe withdrawal and more drop outs were found in the placebo group.
The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted.

Authors' conclusions

Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use.

 

Plain language summary

Methadone at tapered doses for the management of opioid withdrawal

Abuse of opioid drugs and dependence on them causes major health and social issues that include transmission of HIV and hepatitis C, increased crime and costs for health care and law enforcement, family disruption and lost productivity. Addicts, particularly those aged 15 to 34 years, are also at higher risk of death. Managed withdrawal (or detoxification) is used as the first step in treatment. Withdrawal symptoms include anxiety, chills, muscle pain (myalgia) and weakness, lethargy and drowsiness and various pharmacological agents can be used to reduce them. Persisting sleep disturbances and drug craving can continue for weeks and months after detoxification and often lead to relapse to opioid use. The number of addicts who complete detoxification tends to be low, and rates of relapse to opioid use following detoxification are high.
For a tapered dose treatment, illicit opioids are substituted with methadone or another agent under medical supervision in decreasing doses. The review authors searched the medical literature and identified 16 controlled trials involving 1187 adult opioid users in various countries. Trial participants were randomised to receive methadone or another pharmacological treatment over 3 to 30 days. The other treatments were adrenergic agonists including clonidine (11 studies), opioid agonists such as buprenorphine and LAAM (four studies) and chlordiazepoxide (one study). In the one study that compared methadone with placebo, withdrawal symptoms were more severe and more drop outs were found in the placebo group. The methadone starting dose ranged from 20 to 58 mg/day (mean 29 mg/day). Withdrawal symptoms were reduced with methadone but the majority of people relapsed to heroin use. There was no clear difference in completion of treatment or abstinence at follow up with the different agents. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness although symptoms experienced by participants differed according to the medication used and the program adopted. Treatment with adrenergic agonists was associated with lower mean blood pressure (postural hypotension) than with methadone, from five trials.

 

摘要

背景

以逐步調降劑量的美沙酮處置鴉片戒斷症狀

儘管普遍使用於許多國家，在處理鴉片戒斷症狀，逐漸減少美沙酮效力的證據尚未被系統性的評估。

目標

評估在處理完全解毒和復發率的鴉片戒斷症狀，比較逐漸減低美沙酮與其他解毒治療和安慰劑的效果。

搜尋策略

我們搜尋：Cochrane Central Register of Controlled Trials，(The Cochrane Library 第1期，2005)，MEDLINE(1966年1月至2004年12月)，EMBASE(1988年1月至2004年12月)，PsycINFO(1985年1月至2004年12月)，以及參考文獻目錄的文章。我們還聯繫在這領域的製造商和研究人員。

選擇標準

所有隨機對照試驗的重點放在利用減少美沙酮和所有其他戒毒治療藥物或安慰劑來治療鴉片戒斷症狀。

資料收集與分析

兩名評論者評估了納入的研究。對於任何懷疑關於怎麼對研究估計，由與第三個評論者討論解決。研究的品質，根據在Cochrane回顧手冊(Alderson 2004)的標準進行評估。

主要結論

1187人被納入16個試驗中。比較美沙酮與任何其他藥物治療，我們觀察到在完成治療的兩項處置，沒有任何臨床上的差異，相對危險度(RR)1.12; 95％CI為0.94至1.34和成果的後續追蹤，RR 1.17; 95％CI為0.72至1.92。把其他成果的數據集合在一起是不可能的，但研究結果在考慮的治療上並沒有顯示明顯差異。這些結果還證實，當我們考慮的唯一比較：美沙酮和腎上腺素受體激動劑(11項研究)，其他鴉片激動劑(4項研究)，chlordiazepoxide(研究)。美沙酮與安慰劑比較(一項研究)，安慰劑那一群有更嚴重的戒斷和更多的病患退出研究。結果顯示，納入研究中的藥物有著類似的整體成效，雖然參與者經歷的症狀，根據藥物的使用和計畫的採用而有所不同。

作者結論

從文獻資料，都難以相比。計畫持續的時間，設計和治療目標，損害的系統分析應用，都有很大不同的差異。包括這個回顧的研究證實了，緩慢減低暫時性替代的長效鴉片類藥物，伴隨著醫療監督和輔助藥物，可以減輕戒斷的嚴重性。不過多數病患仍再度使用海洛因。

翻譯人

本摘要由高雄榮民總醫院洪碧蓮翻譯。

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

總結

鴉片類藥物濫用和依賴，帶來了很大的健康和社會問題，其中包括愛滋病毒和C型肝炎的傳播，增加犯罪，醫療保健成本和律法的執行，家庭破裂和生產力的損失。吸毒者，特別是那些年齡在15至34歲，也是造成死亡高危險群。處理戒斷(或解毒)被當作治療的第一步。戒斷症狀包括焦慮，發冷，肌肉痛(肌痛)和虛弱，嗜睡和昏睡，使用各種藥物可以用來降低這些症狀。持續性的睡眠障礙和毒品的渴望，在解毒後可繼續幾個星期至幾個月，往往導致鴉片再度使用。能完全戒毒的吸毒者往往是少數，在解毒之後，鴉片使用的復發率比率是高的。對於減低劑量的治療，非法鴉片類在降低劑量的醫生監督下，以美沙酮或其他藥物取代。這篇回顧的作者搜尋醫學文獻，並確定了16個對照試驗，涉及1187個成人，在不同的國家的鴉片使用者。試驗參與者隨機接受美沙酮或其他藥物治療超過3至30天。在其他治療方法包括了腎上腺素受體激動劑clonidine(11項研究)，鴉片受體激動劑包括buprenorphine及LAAM (四項研究)和chlordiazepoxide(一項研究)。在一項研究中，美沙酮與安慰劑相比，發現安慰劑組，戒斷症狀更嚴重和更多病患退出研究。美沙酮開始劑量為20至58毫克/天(平均29毫克/天)。戒斷症狀隨著美沙酮使用而減少，但大多數人因再度使用海洛而症狀復發。在完成治療或追蹤在不同物質禁用上，沒有明顯的差別。結果指出，在納入研究中所使用的藥物有著類似的整體成效，雖然參與者經歷的症狀，根據藥物的使用和計畫的採用而有所不同。從五個試驗中得知，以腎上腺素受體激動劑治療與美沙酮相比，與降低平均血壓(姿勢性低血壓)比較有相關。