Out-of-hospital mortality among patients receiving methadone for noncancer pain.

摘要: Methadone, a µ-opioid agonist long used as evidence-based treatment for opioid dependence,1 has been increasingly prescribed chronic pain. In 2009, 4.4 million methadone prescriptions in the U.S. were of pain, accounting 9% analgesics on dose-adjusted basis.1 Methadone's primary advantages an analgesic are elimination half-life,2 and low cost;1 however, its efficacy is comparable to that other long-acting opioids.3 There major concerns regarding methadone's relative safety. The risk accidental overdose lethal respiratory depression may be greater than opioids. Because duration depressant effects longer effects,4;5 inadvertent intoxication can occur dose increased provide pain relief. This exacerbated by highly variable pharmacokinetics.4;5 2006, FDA issued advisory label was modified warn potential unintentional overdose.5–7 concern reinforced autopsy series deaths with over-representation methadone-related cases8;9 study demonstrating disproportionate number prescription-opioid-related involvement.1 Methadone also adverse cardiac effects. It prolongs QT interval10 implicated numerous case reports life-threatening ventricular arrhythmias.10–13 Cases sudden death, majority which due arrhythmias,14;15 have reported patients.16 These data led questions appropriateness widespread use particularly given equally effective alternatives.1;3;17 However, one cohort comparing sustained-release (SR) morphine unexpectedly found adjusted overall mortality 44% lower users.18 Given this controversy, we conducted patients receiving either or SR non-cancer multiple mechanisms could increase mortality, endpoint total during followup.