Torsades De Pointes Induced by Methadone and Clonazepam Use

Background: While recent data showed that illicit drug use rates at six months of treatment with either methadone or buprenorphine were comparable among patients [1] and that slow-release oral morphine was not inferior to methadone as detoxification treatment [2], methadone continues to be commonly prescribed in drug addiction centers [3]. The compound was developed in Germany in 1937, by scientists who sought to solve Germany's longstanding opioid shortage and derive a synthetic opium from readily available precursors [4]. According to the most recent CDC statistics, between the period of 1999 to 2006, the number of deaths from opioid pain relievers more than tripled in the U.S., from 4,000 to 13,800. Of these, deaths from methadone overdose increased from 790 to 5,420 individuals. Methadone was involved in approximately one in three opioid-related overdose deaths [5]. This medication has been implicated in prolongation of the QT interval which may predispose to Torsades de Pointes, a fatal cardiac arrhythmia. The mechanism of QT prolongation by methadone, is thought to be the result of inhibition of the hERG K+ channel [6].