Methadone: a new old drug with promises and pitfalls.

Although methadone is not a new medication, its use in pain management has increased rapidly over the past decade. This article reviews the unique pharmacologic properties of methadone, including its long-acting nature, highly variable clearance rate, and its antagonism of the N-methyl-D-aspartate receptor. We discuss potential benefits and risks of methadone over other opioid medications. Preclinical studies suggest methadone may reduce abuse potential, tolerance development, and sensitization of nociceptive pathways. Pharmacologic properties of methadone suggest potential greater risk of dangerous or fatal side effects from overdose, QT interval prolongation, and drug interactions. However, clinical studies have yet to confirm that methadone produces either better clinical outcomes or higher rates of adverse events than other opioid analgesics. Clinicians who understand the special properties of methadone and follow recommended precautionary prescribing and monitoring practices can safely and effectively use methadone for pain treatment.