美沙酮相关死亡在阿片类中居首位

根据美国疾病预防控制中心(CDC)的最新数据，尽管在2009年的阿片类药物处方中美沙酮只占不足2%，但2009年美国阿片类药物相关死亡中却有多达30%以上与美沙酮有关，在止痛药中仅次于羟考酮。

美沙酮过量所致死亡率之所以如此高，在很大程度上是由于美沙酮比其他阿片类药物更容易导致过量。例如，美沙酮可以在体内累积而导致严重呼吸抑制。美沙酮还能对心脏节律产生重大干扰。

CDC主任Thomas R. Frieden博士在新闻发布会上指出：“美沙酮在不同的身体中会产生不同的作用，因此有可能某些人只服用较小剂量就会使药物在体内蓄积数日，并导致严重的健康问题。”Frieden博士认为，美沙酮过量死亡例数的增加，主要是由于该药在止痛治疗中的使用增加，而非在戒毒项目中的使用。上述结果发表在7月3日《发病率与死亡率周报》上(MMWR 2012;61:1-5)。

根据CDC、美国食品药品管理局(FDA)、美国缉毒署的全国数据，以及参加了药物滥用警报网络的13个州的数据，美沙酮用于止痛的年处方量在2008年升至1.5份处方/100人，并在2009年保持这一水平。与此同时，该药相关死亡率2007年为1.8例死亡/100,000人，在此后2年内略有下降。1999~2009年期间，涉及美沙酮的药物过量死亡例数增加了5.5倍。2009年美国3,294例阿片类药物相关死亡中，31.4%涉及美沙酮。

卫生官员敦促临床医生避免在缺乏相关经验的情况下开具美沙酮处方，并应限制其仅用于收益大于风险的领域，如癌症疼痛治疗或姑息治疗。

CDC研究者指出，目前美沙酮在疼痛治疗方面的应用可能是不恰当的。FDA的一项研究显示，肌肉骨骼问题，如背痛和关节炎，是2009年美沙酮用于止痛的最常见相关诊断。研究者呼吁临床医生不要为下背痛开具美沙酮处方，原因是研究并未显示使用阿片类药物治疗下背痛有益。

美沙酮也不应用于急性疼痛或阿片类药物初治患者，并且应避免用于正在服用苯二氮卓类药物的患者，以免导致严重呼吸抑制。

Frieden博士说：“美沙酮有很多种更安全的替代品，我们应在确保美沙酮仍能合理治疗成瘾和疼痛的同时解决美沙酮过量死亡的问题。”

研究表明2008年和2009年美沙酮相关过量死亡略有减少，Frieden博士将其归因于政府在减少大剂型美沙酮供应和改善其标签样式方面的努力，但他同时强调仍有很多工作要做。作为临床医生，应当遵循指南使用美沙酮和其他阿片类药物，包括筛查物质滥用。CDC官员还敦促保险公司和制药公司也在这一问题上作出努力。

这项研究由CDC国家伤害预防与控制中心的研究人员开展。

爱思唯尔  版权所有

By: MARY ELLEN SCHNEIDER, Family Practice News Digital Network

Methadone was involved in more than 30% of opioid-related deaths in the United States in 2009, second only to the painkiller oxycodone, according to new data from the Centers for Disease Control and Prevention.

The high rate of overdose deaths from methadone occurred even though the drug accounted for less than 2% of opioid prescriptions in 2009. Part of problem is that methadone is more likely than other opioids to cause an overdose, according to the CDC. For example, a toxic level of methadone can accumulate in the body, leading to severe respiratory depression. Methadone can also cause major disturbances in cardiac rhythm.

"It acts differently in different people’s bodies," Dr. Thomas R. Frieden, director of the CDC, said during a press conference to announce the new data. "So it’s possible that someone can take just a small amount, but it may last for days in their system and cause serious health problems."

 Dr. Frieden noted that the increase in overdose deaths from methadone is primarily due to increased use of the drug in pain treatment, not as part of addiction treatment programs.

The findings, which were published on July 3 in Morbidity and Mortality Weekly Report, show that as the use of methadone for pain relief has risen, so has the number of overdose deaths associated with the drug (MMWR 2012;61:1-5).

The annual rate of methadone prescriptions for pain rose to 1.5 per 100 persons in 2008 and held steady in 2009. At the same time, the mortality for the drug reached 1.8 deaths per 100,000 persons in 2007 and then dropped slightly in the next 2 years. Between 1999 and 2009, the number of overdose deaths involving methadone increased 5.5 times. Methadone was involved in 31.4% of the 3,294 opioid deaths in the United States in 2009.

The findings are based on national data from the CDC, the Food and Drug Administration (FDA), and the Drug Enforcement Administration, as well as data from 13 states that are part of the Drug Abuse Warning Network.

Health officials urged physicians not to prescribe the drug unless they had experience with it, and to limit its use to areas where the benefits outweigh the risks, such as in the treatment of cancer pain or for palliative care.

In the MMWR article, the CDC researchers said that the current uses of the drug in pain treatment might be inappropriate. They pointed to a study from the FDA showing that musculoskeletal problems such as back pain and arthritis were the most common diagnoses associated with methadone use for pain in 2009. The researchers specifically urged physicians not to prescribe methadone for low back pain because studies have not shown benefits to using opioids for this condition.

Methadone also should not be prescribed for acute pain or to opioid-naive patients, and should be avoided in patients taking benzodiazepines because of the risk for severe respiratory depression, according to the researchers.

"There are plenty of safer alternatives to methadone," Dr. Frieden said. "We want to ensure that methadone remains available for appropriately treating addiction and pain and also address the thousands of overdose deaths involving methadone."

The study showed a slight decrease in methadone-related overdose deaths in 2008 and 2009, which Dr. Frieden attributed to government efforts to reduce the availability of high-dose forms of methadone and improve its labeling. But there’s still more work to do, he said.
 
Physicians can do their part by following guidelines for prescribing methadone and other opioids, including screening for substance abuse, he said.

CDC officials urged insurers and pharmaceutical companies to play a role as well. For example, insurers could require authorization for starting doses of methadone for pain that exceed 30 mg/day and stop including methadone on formularies as a preferred drug for the treatment of chronic noncancer pain. Health officials also called on pharmaceutical companies to introduce a low-dose formulation of methadone.

The study was conducted by researchers from the National Center for Injury Prevention and Control at the CDC.