Opioids for neuropathic pain

 

Abstract

Background

The use of opioids for neuropathic pain remains controversial. Studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment.

Objectives

To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain.

Search methods

We searched the Cochrane Central Register of Controlled Trials (2nd Quarter 2005), MEDLINE (1966 to June 2005), and EMBASE (1980 to 2005 Week 27) for articles in any language, and reference lists of reviews and retrieved articles.

Selection criteria

Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded.

Data collection and analysis

Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects.

Main results

Twenty-three trials met the inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = eight to 70 days; n = 9). The short-term trials had contradictory results. In contrast all nine intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. Meta-analysis of seven intermediate-term studies showed mean post-treatment visual analog scale scores of pain intensity after opioids to be 13 points lower on a scale from zero to 100 than after placebo (95% confidence interval -16 to -9; P < 0.00001). The most common adverse events were nausea (33% opioid versus 9% control: number needed to treat to harm (NNH) 4.2) and constipation (33% opioid versus 10% control: NNH 4.2), followed by drowsiness (29% opioid versus 12% control: NNH 6.2), dizziness (21% opioid versus 6% control: NNH 7.1), and vomiting (15% opioid versus 3% control: NNH 8.3). Where reported, 23 (11%) of 212 participants withdrew because of adverse events during opioid therapy versus nine (4%) of 202 receiving placebo.

Authors' conclusions

Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain, whereas intermediate-term studies demonstrate significant efficacy of opioids over placebo, which is likely to be clinically important. Reported adverse events of opioids are common but not life threatening. Further randomized controlled trials are needed to establish long-term efficacy, safety (including addiction potential), and effects on quality of life.

 

Plain language summary

Opioids for neuropathic pain

Opioids, pain killers such as morphine, are effective for the treatment of long-term pain due to nerve damage. Neuropathic pain, pain caused by nerve damage, is often difficult to diagnose and treat. The use of opioids (strong pain killers such as morphine) to treat neuropathic pain is controversial owing to concerns about addiction and beliefs that this type of pain does not always respond well to opioids. The review authors looked at both short- and intermediate-term trials. They found mixed results regarding the effectiveness of short-term use of opioids. Intermediate-term trials demonstrated that opioids are effective for the subtypes of neuropathic pain tested and for the relatively short duration of published studies. Side effects such as nausea, dizziness, and drowsiness were common, but not life threatening.

 

摘要

背景

使用鴉片類藥物治療神經性疼痛

使用鴉片類藥物治療神經性疼痛仍有爭議。研究上已有小小的但卻模棱兩可的結果，且未建立此治療之長期風險效益比率。

目標

評估使用鴉片類藥物治療神經性疼痛的療效與安全性。

搜尋策略

我們收尋了Cochrane Central Register of Controlled Trials ﹝2005年第二季﹞、MEDLINE﹝1966至2005年6月﹞及EMBASE﹝1980至2005年27週﹞等資料庫中任何語言的文章，及列於評論及檢索論文中之參考文獻。

選擇標準

我們收納了接受鴉片類藥物治療之週邊或中樞性神經疼痛，且使用有效儀器來評估疼痛及有報告之不良事件。但是，鴉片類藥物合併其它藥物治療或是使用硬脊膜外或脊髓內給與鴉片類藥物治療者，不收納在本報告中。

資料收集與分析

此資料摘錄於兩位不同的審查者，內容包括了人口統計的變異、診斷、療效與副作用。

主要結論

符合內入條件的共有23篇，並將其歸類為短期研究(小於24小時之研究有14篇)與中期研究(研究期間從8 – 70天，平均為28天之研究共有9篇)。在短期研究之結論並不一致。相反的在中期研究之9篇文獻的研究結果證明鴉片類藥物治療自發性神經疼痛相是有效的。且其中有7篇中期研究經統合分析顯示經鴉片類藥物治療後之疼痛強度與給與安慰劑治療之結果，使用0 – 100分之視覺模擬量尺分數評量結果降低了13分(95% 信賴區間從−16到−9; P<0.00001)。最常見之副作用是噁心(鴉片類藥物治療組佔33%，相對控制組佔9%，有4.2需要治療的傷害)，便祕(鴉片類藥物組治療佔33%，相對控制組佔10%，有4.2需要治療的傷害)，嗜睡(鴉片類藥物治療組佔29%，相對控制組佔12%，有6.2需要治療的傷害)，頭暈(鴉片類藥物治療組佔21%，相對控制組佔6%，有7.1需要治療的傷害)，嘔吐(鴉片類藥物治療組佔15%，相對控制組佔3%，有8.3需要治療的傷害)。這些報研究報告中有212位受試者因接受鴉片類藥物治療產生副作用而退出研究共有23位(佔11%)，另有202位受試者因接受安慰劑治療產生副作用而退出研究共有9位(佔4%)。

作者結論

鴉片類藥物降低神經性疼痛強度的效果在短期研究上僅提供模棱兩可而不確定的結果。然而中期研究證明鴉片類藥物治療神經性疼痛相對安慰劑之結果是明顯有效的，這個結論對臨床而言是很重要。根據報告顯示副作用是很常見，但不會威脅生命之安全。需更進一步進行隨機對照試驗建立長期使用鴉片類藥物的有效性與安全性(包括成癮作用)及對生活品質的改善之效果。

翻譯人

本摘要由三軍總醫院謝凱芝翻譯。

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

總結

擁有疼痛殺手之稱的鴉片類藥物諸如嗎啡等對於因神經受損後所造成長期疼痛之治療是有效的。神經受損後所造成神經性疼痛是難以診斷與治療。縱使擁有疼痛殺手之稱的鴉片類藥物(諸如嗎啡)，由於其具成癮的副作用與不同種類疼痛之治療反應亦有所不同的問題，使用鴉片類藥物來治療神經性疼痛尚無定論。根據短期與中期之研究來判斷得到複雜的結果，短期使用鴉片類藥物的結果尚未確立。中期之研究證明對某些神經性疼痛(對已發表之相對短期之治療)亦是有效。至於噁心、頭暈、嗜睡等副作用是很常見，但不至於有生命威脅。