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作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　October 19, 2009 — 根據線上發表於10月7日版Cochrane Database of Systematic Reviews的系統性回顧結果，即使是嚴重骨關節炎病患，都不應長期使用非tramadol類鴉片類藥物。
　　
　　瑞士柏恩大學的Eveline Nuesch等人寫道，骨關節炎是最常見的關節疾病，也是年長者疼痛和生理失能的主要原因。如果病患發生嚴重疼痛或者其他止痛藥物有使用禁忌時，鴉片類藥物是可用的治療選項。不過，有關這類藥物的效果和安全性的證據相互矛盾。
　　
　　本研究的目標是，對於髖骨或膝蓋骨關節炎的病患，比較口服和經皮吸收的鴉片類藥物及安慰劑，也與不採取治療進行比較止痛效果和功能性效果及安全性。回顧者搜尋CENTRAL、MEDLINE、EMBASE與CINAHL (至2008年7月28日止)，以及檢視文獻的會議活動和參考書目，他們也連絡研究作者，以獲取進一步的資料。
　　
　　納入規範為隨機或準隨機控制試驗、沒有語言限制，比較除了tramadol之外的口服或經皮吸收鴉片類藥物與安慰劑或未採取治療的髖骨或膝蓋骨關節炎病患。一式兩份摘錄資料，計算標準化均數差(SMDs)以及95%信心區間(CI)來探討疼痛和功能性結果與風險，藉以分析安全性結果。使用變異數倒數隨機效果統合分析來合併各個試驗。
　　
　　納入的10個試驗中，共有2,268名研究對象，4篇試驗研究口服的oxycodone、3篇試驗研究口服的可待因、1篇研究經皮吸收的fentanyl、1篇試驗研究口服的嗎啡、2 篇試驗研究口服的oxymorphone。相較於控制型介入方式，鴉片類藥物提供比較好的疼痛緩解效果(SMD，–0.36；95% CI，–0.47至–0.26)與功能改善(SMD，–0.33；95% CI，–0.45至–0.21)。效果並未因鴉片類藥物類型、止痛強度、每日劑量、治療或追蹤期間、研究方法之品質或資金類型而有顯著改變。
　　
　　相較於控制組病患，使用鴉片類藥物者比較會有副作用。就任何副作用來說，彙總的風險比為1.55 (95% CI，1.41 - 1.70；4篇試驗)。因為副作用而退出研究的彙總風險比為4.05 (95% CI，3.06 - 5.38；10篇試驗)、因為嚴重副作用而退出研究的彙總風險比為3.35(95% CI，0.83 - 13.56；2篇試驗)。停止fentanyl治療是因為與安慰劑相比，有比較嚴重的戒斷症候群(SMD，0.60；95% CI，0.42 - 0.79；1篇試驗)。
　　
　　回顧作者寫道，非tramadol類鴉片類藥物的利益只有小到中度，但是副作用風險大大增加。因此，即使是嚴重骨關節炎病患，都不應長期使用非tramadol類鴉片類藥物。
　　
　　研究限制包括，多數試驗是由藥廠資助，因此無法排除可能的出版偏差。
　　
　　回顧作者結論表示，建議醫師使用非tramadol類鴉片類藥物時要謹慎，且可考慮其他治療方式，如手術。此外，醫師應告知病患鴉片類藥物治療實際的相關風險且只有中度助益，也要告知其他治療選項。
　　
　　柏恩大學社會與預防醫學研究中心、瑞士國家科學基金會支持本研究。回顧作者群皆宣告沒有相關財務關係。
　　
　　Cochrane Database Syst Rev. 線上發表於2009年10月7日。

Nontramadol Opioids Should Not Be Routinely Used for Osteoarthritis

By Laurie Barclay, MD
Medscape Medical News

October 19, 2009 — Nontramadol opioids should not be routinely used for osteoarthritis even if pain is severe, according to the results of a systematic review reported online in the October 7 issue of the Cochrane Database of Systematic Reviews.

"Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly," write Eveline Nuesch, from the University of Bern in Bern, Switzerland, and colleagues. "Opioids may be a viable treatment option if patients suffer from severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory."

The goal of this study was to compare oral or transdermal opioids vs placebo or no intervention in patients with osteoarthritis of the hip or knee, in effects on pain and function and safety. The reviewers searched CENTRAL, MEDLINE, EMBASE, and CINAHL (up to 28 July 2008), as well as conference proceedings and bibliographies of identified articles, and they contacted study authors for additional data when indicated.

Inclusion criteria were randomized or quasi-randomized controlled trials, without language restrictions, comparing oral or transdermal opioids other than tramadol vs placebo or no treatment in patients with knee or hip osteoarthritis. Data were extracted in duplicate and standardized mean differences (SMDs), and 95% confidence intervals (CI) were calculated for pain and function and risk ratios for safety outcomes. Inverse-variance random-effects meta-analysis was used to combine trials.

Of 10 trials included, enrolling a total of 2268 participants, 4 trials studied oral oxycodone, 3 trials studied oral codeine, 1 studied transdermal fentanyl, 1 studied oral morphine, and 2 studied oral oxymorphone. Compared with control interventions, opioids offered better pain relief (SMD, –0.36; 95% CI, –0.47 to –0.26) and improvement of function (SMD, –0.33; 95% CI, –0.45 to –0.21). Efficacy did not vary markedly based on opioid type, analgesic potency, daily dose, duration of treatment or of follow up, methodologic quality of studies, or type of funding.

Compared with patients in control groups, those receiving opioids were more likely to have adverse events. For any adverse event, pooled risk ratio was 1.55 (95% CI, 1.41 - 1.70; 4 trials). Pooled risk ratios were 4.05 for study dropout because of adverse events (95% CI, 3.06 - 5.38; 10 trials) and 3.35 for serious adverse events (95% CI, 0.83 - 13.56; 2 trials). Stopping fentanyl treatment was associated with more severe withdrawal symptoms vs placebo (SMD, 0.60; 95% CI, 0.42 - 0.79; 1 trial).

"The small to moderate beneficial effects of non-tramadol opioids are outweighed by large increases in the risk of adverse events," the review authors write. "Non-tramadol opioids should therefore not be routinely used, even if osteoarthritic pain is severe."

Limitations of this study include funding of most of the trials by the pharmaceutical industry and inability to exclude potential publication bias.

"Clinicians are advised to use non-tramadol opioids cautiously and to consider alternatives, such as surgery," the review authors conclude. "In addition, clinicians should inform patients about the substantial risks and only moderate benefits of opioid treatment and therapeutic alternatives."

The Institute of Social and Preventive Medicine at the University of Bern and the Swiss National Science Foundation in Switzerland supported this study. The review authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online October 7, 2009.