First Do No Harm … Reduction?

Illicit opioid use exacts a tremendous toll in health and human suffering. In the United States, heroin and prescription opioid abuse and dependence affect more than 5 million persons, at great human and societal cost (1). Addiction is now understood to be a chronic relapsing condition with deep physiologic roots, and pharmacotherapies that effectively treat opioid dependence are acknowledged to be first-line treatment for this often devastating disorder (2).

Methadone is the medication most widely used to treat opioid dependence. Its efficacy has been established in diverse settings and across multiple outcomes, including reductions in mortality, HIV infection, incarceration, and costs. Extensive federal regulations govern methadone treatment, which is delivered to approximately 260 000 persons nationally by a heterogeneous mix of more than 1100 methadone treatment programs (3). Although mounting evidence supports integrating methadone treatment with medical and mental health services, most treatment programs provide minimal on-site medical care (4).

Two significant issues concerning methadone safety have emerged in recent years: An increase in methadone-related deaths and evidence that methadone is associated with prolongation of the QT interval. The rise in methadone-associated deaths seems in large measure to reflect multisubstance overdoses among persons who access methadone that was prescribed to treat pain, which reflects its growing use as an analgesic outside of methadone maintenance treatment programs (5). Although evidence of methadone's possible effect on the QT interval has been accumulating, it has remained unclear how to incorporate such information into clinical practice. …