作者：Susan Jeffrey
出處：WebMD醫學新聞
September 11, 2008（田納西州，那什維爾訊）－一項新研究顯示，慢性疼痛病患使用methadone劑量與血中濃度之間的關連不佳。研究團隊指出，這項發現致使與使用methadone造成死亡人數變多所得到的因果關係結論變得複雜化。
研究作者、加州西柯汶納Veract難治型疼痛診所Forest Tennant醫師向Medscape神經學與神經外科學表示，我們發現使用非常高劑量methadone的病患，其血中濃度很低，而血中濃度非常高的病患，使用的劑量卻很低，這樣的差異確實是很戲劇化的。
他指出，他們的發現顯示，與methadone有關的死亡事件，已經證實與血中濃度過高的，可能不盡然是methadone過量的直接結果，不見得與使用methadone有關，或許是其他藥物或其他疾病造成的；把焦點放在methadone身上顯然是有點不恰當。
這項研究發表於第19屆美國疼痛處理學會年度臨床會議上。
【在適當的訓練下是有效的止痛藥物】
Tennant醫師寫道，過去幾十年來，使用methadone治療慢性疼痛病患猝死病例數目持續增加；他附帶表示，這些死亡事件由驗屍官做出一般的解釋是在解剖時於血液中發現methadone，且與methadone過量或毒性有關。其毒性反應最常被認為與心臟傳導異常有關。他在訪談中表示，他們做出的結論是，這可能是methadone引起的，也可能不是。
在這項研究中，Tennant醫師收納了44位罹患慢性疼痛的病患，這些病患每天服用methadone，持續4個月，他們並沒有因為治療而使臨床功能受損或是被鎮靜；他表示，病患們服用methadone並沒有特別問題，可以開車、正常作息，他們的生活就像一般人一樣好，但是卻有嚴重慢性疼痛。
他接著建立病患們的methadone劑量，監測他們的methadone血中濃度，並試著連結兩者之間的關係；Tennant醫師表示，這兩者之間沒有絕對關係。
每日的methadone劑量從40 mg到600 mg，而血中濃度從60 ng/ml到2580 ng/ml。
Tennant醫師的結論是，這些數據質疑了每日methadone劑量、血中濃度與毒性必須相關的前提；當服用methadone的慢性疼痛病患死亡時，其死因不要僅假設這是使用methadone過量或是毒性反應。
他推測這些死亡事件可能與這些病患重複用藥有關，這些病患可能已經接受抗憂鬱藥物與其他藥物治療，或是methadone起始劑量過高，而不是劑量增加地太快；然而，他指出，其研究中有44位病患顯示methadone在醫師適當地使用下可以是非常安全且有效的藥物。
目前罹患慢性疼痛的族群中，包括那些有脊椎損傷或是其他脊椎問題的病患，這些病患大約佔了一半，而另一半則區分為有免疫問題，例如纖維肌痛、其他形式的神經受損、或是頭痛；他指出，這幾年來包括初級照護、內科醫師等許多醫師已經開始因為大眾需求而治療這些疼痛。
然而，在他們處方長效類鴉片類藥物時，例如methadone，在我的意見，他們必須要接受一些訓練，不僅僅只是聽演講，他們必須接受有使用這些長效鴉片類藥物經驗的醫師現場、親自的訓練。
【有關聯但非因果關係】
當被問到對這些發現的評論時，加州大學戴維斯醫學院麻醉學與疼痛醫學教授Scott Fishman醫師同意，與使用methadone有關死亡事件的增加表示methadone治療確實有問題；然而，他附帶表示，抽血檢驗methadone血中濃度來證實其因果關係，特別是在目前這項研究的發現，仍然是未明的。
Fishman醫師指出，Methadone過去被用於海洛英濫用維持療法，但是最近則被作為非常有效的止痛藥物，因為他們很便宜；因此病患開始使用這個藥物，但他們不知道methadone與其他我們使用的鴉片類藥物是非常不同的，因為其藥理性質獨特；Methadone的藥物交互作用也不同，不同的干擾因子可能造成血中濃度上升或下降，且基本上其代謝物相較於其他鴉片類藥物來說是不穩定的。
他表示，其中一個問題是，當病患從其他鴉片類藥物轉換到methadone時，很難計算出他們將會需要多少methadone，因此他們應該從低濃度開始慢慢向上增加劑量，有時候並沒有緩慢地增加劑量；這些病患可能處於風險，特別是那些有呼吸問題或是睡眠呼吸中止症的病患，因為methadone的半衰期比較長。
Fishman醫師的結論是，安全地且正確地使用，methadone可以是非常安全、非常有效的，但是這需要許多關心與風險管理。
這項研究並未接受藥廠贊助。Tennant醫師表示與這項發表並無相關公開事項。Fishman醫師報告他接受Elan、Endo藥廠、Janssen醫療事務公司、默克、輝瑞與Purdue藥廠的研究經費；且接受Cephalon、Elan、Endo藥廠、Janssen醫療事務、默克、輝瑞與Purdue藥廠與禮來藥廠的顧問費用。
Methadone Dosages Correlate Poorly with Serum Levels
By Susan Jeffrey
Medscape Medical News
September 11, 2008 (Nashville, Tennessee) — A new study shows a poor correlation between dosages of methadone given to chronic pain patients and the resulting serum levels. The findings, the researchers say, complicate any cause-and-effect conclusions that may be drawn in the rising number of deaths associated with methadone use.
"We found people who had very, very high dosages and low blood levels; and people with very high blood levels and low dosages, and the range was rather dramatic, actually," study author Forest Tennant, MD, DrPH, from the Veract Intractable Pain Clinic, in West Covina, California, told Medscape Neurology & Neurosurgery.
Their findings suggest that deaths that have been attributed to methadone because of high blood levels of the drug may not after all be the direct result of methadone overdose but rather the use of methadone in association perhaps with other drugs or underlying conditions, he said. "The finger-pointing at methadone per se appears to be a little misplaced."
The results were presented at the 19th Annual Clinical Meeting of the American Academy of Pain Management.
An Effective Analgesic — With Proper Training
Over this decade, there has been an upsurge in the number of sudden deaths seen among chronic pain patients who have been prescribed methadone, Dr. Tennant writes. The usual explanation for these deaths by coroners who find methadone in the blood at autopsy is "methadone overdose or toxicity," he added. The toxic effect is most commonly thought to occur due to induction of cardiac conduction dysfunction. "They jump to the conclusion that it was methadone, and it may not be," he said in an interview.
In this study, Dr. Tennant enrolled 44 chronic pain patients who had taken methadone daily for over 4 months, without being clinically impaired by treatment or appearing sedated. "They were doing well on methadone — driving a car, functioning normally, leading as good a life as you can lead with such severe chronic pain," he noted.
He then established their daily methadone dosages, measured their serum concentrations of methadone, and tried to correlate the 2. "There was absolutely no correlation," Dr. Tennant said.
Daily methadone dosages ranged from 40 mg to 600 mg per day, and serum concentrations ranged from 60 ng/mL to 2580 ng/mL.
"These data question the premise that daily methadone dosage, blood level, and toxicity are necessarily related," Dr. Tennant concluded. "When death occurs in a pain patient who takes methadone, the cause must not be simply assumed to be an overdose or toxic reaction to methadone."
He speculated that these deaths may be related to polypharmacy in these patients, who may already be treated with antidepressants and other medications, or to methadone dosages started at too high a level, rather than titrating upward over time. However, their study in 44 patients, he noted, has also shown that methadone "can be a very safe and effective drug in the hands of physicians who know what they are doing."
The current population of patients with chronic pain includes those with spine trauma or other spinal conditions, which make up about half of patients, with the other half divided among those with immune disorders such as fibromyalgia, other types of nerve damage, or some headaches. In recent years, many physicians, including primary care physicians and internists, have begun treating pain because of the public demand, he said.
"However, before they prescribe long-acting opioid drugs like methadone, they must in my opinion obtain some training, other than just a seminar. They need to have on-site, hands-on training with physicians who are experienced in using long-acting opioid drugs," he said.
Association Not Causation
Asked for comment on these findings, Scott Fishman, MD, professor of anesthesiology and pain medicine at the University of California, Davis School of Medicine, agreed that the rise in deaths related to methadone suggests there is a problem with methadone treatment. However, the cause and effect that has been drawn from serum levels of methadone, particularly in light of the current findings, is not clear, he added.
Methadone was previously used for heroin maintenance but has more recently been used as a very effective analgesic, particularly since it is inexpensive. "So people started to use it, and they didn't realize that methadone is a very different opioid from the other opioids that we use, because it has different pharmacological properties," Dr. Fishman said. "It has different drug interactions, different interferences that might cause serum levels to go up or down, and it's basically metabolically unstable relative to other opioids."
One of the problems, he said, is that when patients are switched to methadone from another opioid, it is difficult to know how much methadone they will require, so they should be titrated up slowly from low levels. "These slow titrations sometimes aren't done," he noted. These patients can be at risk, particularly those who have breathing problems or obstructive apnea, because methadone has a long half-life.
"Used carefully and correctly, methadone can be very, very effective, but it needs to be used with a lot of care and risk management," Dr. Fishman concluded.
The study did not receive pharmaceutical funding. Dr. Tennant reports no disclosures relevant to this presentation. Dr. Fishman reports that he receives research support from Elan, Endo Pharmaceuticals, Janssen Medical Affairs, Merck, Pfizer, and Purdue Pharma; and receives consulting fees from Cephalon, Elan, Endo Pharmaceuticals, Janssen Medical Affairs, Merck, Pfizer, Purdue Pharma, and Eli Lilly.
American Academy of Pain Management 19th Annual Clinical Meeting: Abstract 70. Presented September 8-11, 2008.
[ 本帖最後由 goodcat1111 於 2008-9-21 22:49 編輯 ] |
|
