Methadone Prescribing: Everything You Wanted to Know but Were Afraid to Ask

Ricardo A. Cruciani, MD, PhD

Department of Pain Medicine and Palliative Care
Beth Israel Medical Center
New York, NY
Departments of Neurology and Anesthesiology
Albert Einstein College of Medicine
Bronx, NY

Methadone is a synthetic opioid that is used both as a potent analgesic for chronic pain and as substitution therapy in opioid dependence treatment programs. It is characterized by a complicated pharmacologic profile, which includes activities as an opioid receptor agonist, an N-methyl-d-aspartate receptor antagonist, and a mild inhibitor of norepinephrine and serotonin reuptake. Variable pharmacokinetics necessitate caution when methadone is prescribed for pain management; the half-life of methadone often exceeds its analgesic effects, which can lead to life-threatening respiratory depression days after drug initiation or dose escalation. In addition, the FDA has raised concerns regarding the potential for QTc prolongation and torsade de pointes, a potentially fatal arrhythmia, although the clinical relevance of these effects remains the subject of debate among experts. A session at the 2010 Annual Meeting of the American Pain Society examined recent evidence for the benefits, toxicity, and complications related to the use of methadone, either as an analgesic or as substitution therapy for heroin or opioid addiction.

References

Andrews CM, Krantz MJ, Wedam EF, et al. Methadone-induced mortality in the treatment of chronic pain: role of QT prolongation. Cardiol J. 2009;16(3):210-217.
Cruciani RA. Methadone: to ECG or not to ECG...That is still the question. J Pain Symptom Manage. 2008;36(5):545-552.
Fishman SM, Wilsey B, Mahajan G, Molina P. Methadone reincarnated: novel clinical applications with related concerns. Pain Med. 2002;3:339-348.

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