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作者：Caroline Cassels  
出處：WebMD醫學新聞

　　January 20, 2010 — 新研究認為，使用較高劑量鴉片類藥物治療慢性疼痛的病患，過量的風險幾乎是使用這類藥物劑量最低者的9倍。至少有1位專家因為這些發現而提出呼籲變更目前的疼痛處置與鴉片類止痛藥物開方實務。
　　
　　華盛頓大學團體健康研究中心的研究者發現，在這群開始使用鴉片類止痛藥物治療疼痛的成年人中，使用每天100mg者的過量風險是每天1-20mg者的8.9倍，再者，每天使用50-99mg的病患，其過量風險是劑量最低組的3.7倍。
　　
　　劑量低、中、高組的年度過量率分別是0.2%、0.7%、1.8%。
　　
　　Michael Von Korff領銜的研究作者們寫道，我們觀察發現，使用較高劑量鴉片類止痛藥物的病患，其過量風險增加，多數的過量都造成醫療上嚴重的案例，有12%是致命的。
　　
　　這項研究登載於1月19日的內科醫學誌(Annals of Internal Medicine)。
　　
　　【多數常用的藥物類別】
　　目前，鴉片類止痛藥物是美國最常開方的藥物，根據研究者，長期使用鴉片類止痛藥物治療慢性非癌症性疼痛已經變成普遍，有超過3%的成人接受這類治療，同時，他們指出，鴉片類止痛藥中毒致死的比率也在增加。
　　
　　有些研究認為，鴉片類止痛藥物意外過量致死的案例不到半數是來自醫師的處方，不過，他們指出，病患接受醫師處方之鴉片類止痛藥物的風險並沒有被研究過。
　　
　　研究者試圖評估鴉片類止痛藥物過量的比率，以及過量比率和接受處方長期治療者的每日平均鴉片類止痛藥物劑量之間的關係。
　　
　　研究者利用華盛頓的一個大型健康照護組織、提供預付醫療服務超過500,000人次的藥局紀錄資料，檢視了一群18歲以上、共9,940名開始使用鴉片類止痛藥物的病患。
　　
　　研究對象在1997至2005年間接受至少3次的鴉片類止痛藥處方，治療的狀況包括頸部或背部疼痛、頭痛、下巴痛、關節炎和經痛。
　　
　　該研究的主要結果包括，與每天使用的鴉片類止痛藥物平均劑量有關的致命與未致命過量風險，也根據這些劑量計算年度過量比率。
　　
　　【背痛與四肢疼痛】
　　研究者報告指出，68%的研究對象接受鴉片類止痛藥物治療背痛或四肢疼痛。
　　
　　這個世代中約60%是女性，平均年紀54歲，平均每日處方的鴉片類止痛藥劑量為13.3 mg，最常開方的鴉片類止痛藥物是佔了46%的hydrocodone。
　　
　　總共有51名病患有1次以上的鴉片類藥物相關過量，這些病患中，40人發生致命的(6人)或其他嚴重的過量，11人屬於不嚴重的過量。
　　
　　可能的研究限制包括，實際上過量的案例很少，他們主要是根據給藥紀錄評估，可能會忽略一些案例。
　　
　　此外，研究作者指出，還不清楚過量比率中的劑量相關差異是否與病患差異性有關，或與較高劑量有直接或間接關係。
　　
　　研究作者們寫道，因為不確定效果和風險的關聯，長期使用鴉片類止痛藥物治療時，醫師在處方上應有所警覺，目前雖未發生，但需密切監測病患，後續研究應針對長期使用鴉片類藥物治療的過量風險，以及降低相關風險的方法。
　　
　　【需要更多有反應的處方】
　　華盛頓特區、白宮國家藥物控制政策辦公室的A. Thomas McClellan博士在編輯評論中表示，這些研究發現強調了需要更多有反應的處方實務的需求。
　　
　　McLellan博士指出，原始資料顯示，診斷有憂鬱或物質濫用或同時接受鎮靜安眠藥物處方者的過量風險較高，他指出，已知這3個是鴉片類藥物副作用的風險因素。
　　
　　他寫道，因此，如果開立鴉片類藥物給這些人，他們需要持續的教育與密切關注。
　　
　　此外，他指出，這些研究發現強調了目標導向治療的重要性，例如，持續或增加鴉片類藥物治療劑量需視明顯的功能性改善和生活品質而定，長期治療會有太多風險，而對改善健康狀態沒有幫助。
　　
　　該研究也強調，需要處方藥物監測計畫，以便更容易追蹤病患的鴉片類藥物處方。
　　
　　McLellan博士寫道，病患安全的威脅太大，目前的疼痛處置和鴉片類藥物處方實務必須有所改變。
　　
　　Von Korff醫師報告接受Johnson Johnson藥廠的資金，其他研究者的宣告請見原始文獻，McLellan博士宣告沒有相關財務關係。


Higher Doses of Opioids in Chronic Pain Patients Linked to Increased Overdose Risk

By Caroline Cassels
Medscape Medical News

January 20, 2010 — Individuals who receive higher-dose opioid therapy for chronic pain have almost a 9-fold increased risk for overdose compared with patients who receive the lowest doses of these medications, new research suggests. These findings have at least 1 leading expert calling for change to current pain management and opioid-prescribing practices.

Investigators at the Group Health Research Institute and the University of Washington found that among a cohort of adults who started use of opioid analgesics for a pain condition those receiving 100 mg/day of opioids had an 8.9-fold increase in overdose risk compared with patients receiving 1 to 20 mg/day of these medications. Further, patients receiving 50 to 99 mg/day had a 3.7-fold increase in overdose risk compared with patients in the lowest-dose group.

Annual overdose rate for the high-, medium-, and low-dose groups were 0.2%, 0.7%, and 1.8%, respectively.

"We observed increased risk for overdose in patients receiving medically prescribed opioids at higher doses. Most overdoses were medically serious, and 12% were fatal," the study authors, with lead investigator, Michael Von Korff, ScD, write.

The study is published in the January 19 issue of Annals of Internal Medicine.

Most Commonly Prescribed Class of Medications

Currently, opioids are the most commonly prescribed medication in the United States. According to investigators, long-term opioid therapy for chronic noncancer pain is becoming increasingly common, with more than 3% of adults now receiving such treatment. At the same time, they note that death rates from opioid analgesic poisoning have also increased.

Some research suggests that less than half of individuals who died of unintentional prescription drug overdose received opioids from a physician. However, they point out that the risk in patients receiving medically prescribed opioids has not been studied.

The researchers sought to estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy.

Using pharmacy record data from a large health maintenance organization, which provides prepaid care to more than 500,000 individuals in Washington, investigators identified a cohort of 9940 patients 18 years and older starting a new episode of opioid use.

Study subjects received at least 3 opioid prescriptions during a 3-month period from 1997 through 2005. Patients were being treated for conditions that included neck or back pain, headache, jaw pain, arthritis, and menstrual pain.

The study's primary outcomes included risk for nonfatal and fatal overdose as they relate to average daily opioid dose. Annual overdose rates were also calculated based on dose.

Back and Extremity Pain

The investigators report that 68% of individuals were receiving opioid therapy for back or extremity pain.

Approximately 60% of the cohort were women, with a mean age of 54 years. The mean daily dose of opioids prescribed was 13.3 mg, and at 46% hydrocodone was the most commonly prescribed opioid.

A total of 51 patients had 1 or more opioid-related overdoses. Of these patients, 40 experienced a fatal (6) or otherwise serious overdose and 11 had a nonserious overdose.

Potential limitations of the study include the fact that there were few overdoses and that they were assessed primarily through record review, introducing the possibility that some cases were missed.

In addition, the study authors note, it was not clear from the study whether dose-related differences in overdose rates were related to patient differences or to the direct or indirect effects of higher doses.

"Because of uncertainties regarding effectiveness and risks, long-term opioid therapy should be prescribed with awareness of risk and close patient monitoring, which may not be happening consistently at present. Further research on overdose risks of long-term opioid therapy and approaches to reduce associated risks is needed," the study authors write.

Need for More Responsible Prescribing

In an accompanying editorial, A. Thomas McClellan, PhD, White House Office of National Drug Control Policy, Washington, DC, said the study findings highlight the need for more responsible prescribing practices.

Dr. McLellan notes that the unadjusted data show that there were more overdoses among patients diagnosed as having depression or substance abuse or who were concurrently receiving sedative-prescribed hypnotics. All 3 of these factors, he points out, are well-known risks for adverse events from opioids.

"Therefore, these persons require substantial education and close oversight if opioids are prescribed," he writes.

In addition, he notes, the findings reinforce the importance of goal-directed therapy "such that continued or increased doses of opioid therapy should be contingent on clear improvements in function and quality of life. "Long-term therapy carries too many risks to justify use without improvements in health status."

The study also highlights the need for a prescription-drug monitoring program that makes it easy to track a patient's opioid prescriptions.

"The threat to patient safety is too great to allow current pain management and opioid-prescribing practices to remain as they are," Dr. McLellan writes.

Dr. Von Korff reports that he has grants pending from Johnson Johnson. The disclosures of the other investigators can be found in the original paper. Dr. McLellan has disclosed no relevant financial relationships.

Ann Intern Med. 2010;152:85-92, 123-125.