Department of Medical Oncology, Shaare Zedek Medical Center, Jerusalem, Israel.
Palliat Med. 2011 Jul;25(5):488-93. doi: 10.1177/0269216310397687.
To address the question: is oral methadone better than placebo, or other oral/transdermal opioids in the management of cancer pain?
A literature search was performed to identify relevant studies. Search strategies included: (1) methadone (title) AND placebo (title or abstract) AND pain (title or abstract); (2) methadone (title) AND randomized (title or abstract) AND pain (title or abstract) AND cancer (title or abstract). Papers were reviewed for relevance to first-line opioid therapy.
No studies were identified comparing methadone to placebo for cancer pain. A single study compared methadone to placebo for neuropathic pain and demonstrated evidence of analgesic effect at a dose of 20 mg/day but not at a dose of 10 mg/day. Four studies compared oral methadone to either oral morphine, or oral morphine and transdermal fentanyl in a first-line setting: Gourlay 1986 (N = 18), Ventafridda 1986 (N =54), Bruera 2004 (N = 106) and Mercadante 2008 (N = 108). All studies demonstrated comparable, but not superior, analgesia with, overall, a comparable adverse effect profile. The duration of the study period for the three largest studies was 28 days. Two of these studies, Ventafridda 1986 and Mercadante 2008, indicated that, over time, the opioid escalation index was lower for methadone than for morphine. One study that used a 2:1 dose ratio between morphine and methadone was associated with a high attrition rate in the first week because of excessive sedation. This effect was not seen in the study that used a 4:1 morphine to methadone dose ratio with dose titration.
This limited data suggests that (1) methadone may be an equally effective candidate for first-line opioid therapy, (2) that it is possibly less expensive, (3) that there may be a propensity to sedation and dose accumulation unless there is close monitoring and conservative dose selection and (4) that it should be initiated with a calculated dose based on a morphine to methadone dose ratio of not less than 4:1.
解决以下问题：在癌症疼痛管理中，口服美沙酮是否优于安慰剂或其他口服/透皮阿片类药物？
进行了文献检索以确定相关研究。搜索策略包括：（1）美沙酮（标题）和安慰剂（标题或摘要）和疼痛（标题或摘要）；（2）美沙酮（标题）和随机（标题或摘要）和疼痛（标题或摘要）和癌症（标题或摘要）。评估了这些论文是否与一线阿片类药物治疗相关。
没有研究比较美沙酮与安慰剂治疗癌症疼痛。一项研究比较了美沙酮与安慰剂治疗神经性疼痛，并证明在 20mg/天的剂量下具有镇痛作用，但在 10mg/天的剂量下没有。四项研究将口服美沙酮与口服吗啡或口服吗啡和透皮芬太尼在一线治疗中进行了比较：Gourlay 1986（N=18）、Ventafridda 1986（N=54）、Bruera 2004（N=106）和 Mercadante 2008（N=108）。所有研究均表明，美沙酮具有相当但不优越的镇痛作用，总体不良反应谱相似。这三项最大的研究的研究期持续时间为 28 天。其中两项研究（Ventafridda 1986 和 Mercadante 2008）表明，随着时间的推移，美沙酮的阿片类药物升级指数低于吗啡。一项使用吗啡和美沙酮剂量比为 2:1 的研究，由于过度镇静，在第一周的失访率很高。在使用吗啡和美沙酮剂量比为 4:1 并滴定剂量的研究中，没有观察到这种效应。
这有限的数据表明，（1）美沙酮可能是一线阿片类药物治疗的同样有效候选药物，（2）它可能更便宜，（3）除非密切监测和保守剂量选择，否则可能存在镇静和剂量积累的倾向，（4）应根据吗啡和美沙酮剂量比不小于 4:1 的计算剂量开始。
