Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee.
Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
JAMA Intern Med. 2015 Mar;175(3):420-7. doi: 10.1001/jamainternmed.2014.6294.
Growing methadone use in pain management has raised concerns regarding its safety relative to other long-acting opioids. Methadone hydrochloride may increase the risk for lethal respiratory depression related to accidental overdose and life-threatening ventricular arrhythmias.
To compare the risk of out-of-hospital death in patients receiving methadone for noncancer pain with that in comparable patients receiving sustained-release (SR) morphine sulfate.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using Tennessee Medicaid records from 1997 through 2009. The cohort included patients receiving morphine SR or methadone who were aged 30 to 74 years, did not have cancer or another life-threatening illness, and were not in a hospital or nursing home. At cohort entry, 32 742 and 6014 patients had filled a prescription for morphine SR or methadone, respectively. The patients' median age was 48 years, 57.9% were female, and comparable proportions had received cardiovascular, psychotropic, and other musculoskeletal medications. Nearly 90% of the patients received the opioid for back pain or other musculoskeletal pain. The median doses prescribed for morphine SR and methadone were 90 mg/d and 40 mg/d, respectively.
The primary study end point was out-of-hospital mortality, given that opioid-related deaths typically occur outside the hospital.
There were 477 deaths during 28 699 person-years of follow-up (ie, 166 deaths per 10 000 person-years). After control for study covariates, patients receiving methadone had a 46% increased risk of death during the follow-up period, with an adjusted hazard ratio (HR) of 1.46 (95% CI, 1.17-1.83; P < .001), resulting in 72 (95% CI, 27-130) excess deaths per 10 000 person-years of follow-up. Methadone doses of 20 mg/d or less, the lowest dose quartile, were associated with an increased risk of death (HR, 1.59; 95% CI, 1.01-2.51, P = .046) relative to a comparable dose of morphine SR (<60 mg/d).
The increased risk of death observed for patients receiving methadone in this retrospective cohort study, even for low doses, supports recommendations that it should not be a drug of first choice for noncancer pain.
在疼痛管理中，美沙酮的使用量不断增加，这引发了人们对其与其他长效阿片类药物相比安全性的担忧。盐酸美沙酮可能会增加因意外过量和危及生命的室性心律失常导致致命性呼吸抑制的风险。
比较接受美沙酮治疗非癌性疼痛的患者与接受硫酸吗啡控释片（SR）治疗的可比患者发生院外死亡的风险。
设计、地点和参与者：本回顾性队列研究使用了 1997 年至 2009 年田纳西州医疗补助记录。队列包括接受吗啡 SR 或美沙酮治疗、年龄在 30 至 74 岁之间、没有癌症或其他危及生命的疾病、不在医院或疗养院的患者。在队列入组时，分别有 32742 名和 6014 名患者开出了吗啡 SR 或美沙酮的处方。患者的中位年龄为 48 岁，57.9%为女性，接受心血管、精神药物和其他肌肉骨骼药物的比例相当。近 90%的患者因背痛或其他肌肉骨骼疼痛接受阿片类药物治疗。开出的吗啡 SR 和美沙酮的中位剂量分别为 90mg/d 和 40mg/d。
主要研究终点为院外死亡率，因为阿片类药物相关的死亡通常发生在医院外。
在 28699 人年的随访期间（即，每 10000 人年 166 人死亡）发生了 477 例死亡。在校正研究协变量后，接受美沙酮治疗的患者在随访期间死亡风险增加了 46%，调整后的风险比（HR）为 1.46（95%CI，1.17-1.83；P<0.001），导致每 10000 人年随访中额外死亡 72 人（95%CI，27-130 人）。最低剂量四分位数（美沙酮剂量为 20mg/d 或以下）与死亡风险增加相关（HR，1.59；95%CI，1.01-2.51，P=0.046），而与吗啡 SR 可比剂量（<60mg/d）相比。
本回顾性队列研究观察到接受美沙酮治疗的患者死亡风险增加，即使是低剂量，也支持了不建议将其作为非癌性疼痛的首选药物的建议。
