Methadone is highly effective in treating
opioid dependence, and it is also used as an
analgesic for second-line management of chronic
pain. However, recent increases in
methadone-related deaths have instigated controversy about the use of this medication. In this paper, we evaluate risk factors for
methadone mortality in
opioid dependent and
pain populations and present guidelines for initiating
methadone treatment in these two populations to minimize the risk of death. Early research with
methadone-maintained patients revealed that
methadone fatalities occur primarily due to respiratory arrest during
methadone induction and in the context of polysubstance use. Recent reports of
methadone deaths emphasize
chronic pain populations,
methadone-related QTc prolongation, and the possibility of inducing
Torsade de pointes (TdP), a potentially fatal ventricular
arrhythmia. Retrospective analyses of these deaths show that patients who develop TdP often present with multiple risk factors, including high
methadone doses, use of other medications that cause QTc prolongation, and
electrolyte abnormalities. To minimize fatalities, guidelines are presented for initiating
methadone in
opioid treatment and
pain populations that consider the
drug's pharmacology along with behavioral, medical and psychiatric risk factors.