Methadone for Chronic Pain: Benefits, Complications, and Toxicity

BALTIMORE, Md.—At the American Pain Society 29th Annual Scientific Meeting, a panel discussion on methadone prescribing evaluated the risks and benefits of methadone, individual responses to methadone, and concluded with a review of methadone's potential for cardiotoxicity.

Perry G. Fine, MD, of the University of Utah in Salt Lake City began by reviewing methadone's history, beginning in 1930 to its use today with over 4 million prescriptions written in 2006. Dr. Fine discussed the reasons why methadone treatment in chronic pain may be warranted: the dosing is versatile, there is a long duration of action, it has a favorable metabolic profile, and it is relatively inexpensive. However, the concerns are also prevalent: methadone has a highly variable pharmacokinetic profile, a very long half life that can lead to increased risk for sedation, a non-linear dose conversion, and methadone use requires that prescribers have methadone-specific knowledge, as well as highly responsible patients and caregivers who need to monitor the drugs effects, especially during titration.

Ricardo A. Cruciani, MD, PhD, of Beth Israel Medical Center in New York discussed methadone's ability to prolong the QT interval. Dr. Cruciani stressed that while the body of literature is growing, recognition of the need for EKG screening and monitoring in patients who are candidates for methadone therapy have only recently been introduced and discussed in the literature.

Craig T. January, MD, PhD, from the Division of Cardiovascular Medicine at the University of Madison in Wisconsin discussed studies that showed how QT prolongation is not always methadone dose-dependent and may occur at any dose. One such study was published in 2008 by Sumeet S. Chugh and colleagues and found that methadone, even at therapeutic levels, can be a likely cause of sudden death. These findings further point to the need for clinical safeguards and additional prospective studies specifically designed to enhance the safety of methadone use.

To minimize harm when prescribing methadone and similar drugs, the panel reviewed 8 general guidelines for prescribers such as assessing patients for risk of abuse, watching for comorbid mental disease, using conversion tables cautiously when switching or rotating, avoiding combining certain medications, monitoring titration, assessing for sleep apnea, informing patients to decrease dose during upper respiratory infections, and avoiding concomitant use of long-acting opioids for acute pain.

Overall, the panel concluded that close monitoring of methadone patients is important but may not be feasible for all patients. Questions still remain as to how, when, and at what intervals should methadone patients be monitored.