Circulation 94,429 • Volume 26, No. 2 • Fall 2011   Issue PDF

Methadone References Supplied by Request

Joan M. Christie, MD

In the last issue of this Newsletter (Volume 26, No. 1), Dr. Joan Christie authored an important article addressing the risks of methadone and means to mitigate such risk. Both Dr. Christie and the editors have received correspondence requesting references for this article. These references were omitted from the original article due to space limitations as an editorial decision. In light of the recent requests, we are providing these general pertinent references as follows:

  1. Lemberg K, Kontinen VK, Viljakka K, et al. Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat. Anesth Analg 2006;102:1768-74.
  2. Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med 2010;363:1981-5.
  3. Clark JD. Understanding methadone metabolism: a foundation for safer use. Anesthesiology 2008;108:351-2.
  4. Wells C. Deadly pills’ toll mounting. Sarasota-Manatee Herald-Tribune December 4, 2010. Available at: Accessed August 10, 2011.
  5. Warner M, Chen LH, Makuc DM. Increase in fatal poisonings involving opioid analgesics in the United States, 1999-2006. NCHS Data Brief 2009;(22):1-8. Available at:
  6. Krantz MJ, Martin J, Stimmel B, et al. QTc interval screening in methadone treatment. Ann Intern Med 2009;150:387-95.
  7. Totah RA, Sheffels P, Roberts T, et al. Role of CYP2B6 in stereoselective human methadone metabolism. Anesthesiology 2008;108:363-74.
  8. Crettol S, Déglon JJ, Besson J, et al. Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin Pharmacol Ther 2005;78:593-604.
  9. Adelson M, Peles E, Bodner G, Kreek MJ. Correlation between high methadone doses and methadone serum levels in methadone maintenance treatment (MMT) patients. J Addict Dis 2007;26:15-26.
  10. Li Y, Kantelip JP, Gerritsen-van Schieveen P, Davani S. Interindividual variability of methadone response: impact of genetic polymorphism. Mol Diagn Ther 2008;12:109-24.
  11. Methadone: Drug Information. UpToDate®. Lexi-Comp, Inc. 1978-2010. Available at: Accessed August 10, 2011
  12. Public health advisory: methadone use for pain control may result in death and life threatening changes in breathing and heart rate. FDA US Food and Drug Administration. November 27, 2006. Available at: Accessed August 10, 2011.
  13. Ansermot N, Albayrak O, Schläpfer J, et al. Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval. Arch Intern Med 2010;170:529-36.
  14. Regenthal R, Krueger M, Koeppel C, Preiss R. Drug levels: therapeutic and toxic serum/plasma concentrations of common drugs. J Clin Monit Comput 1999;15:529-44.
  15. Krantz MJ, Rowan SB, Schmittner J, et al. Physician awareness of the cardiac effects of methadone: results of a national survey. J Addict Dis 2007;26:79-85.
  16. Trescot AM, Helm S, Hansen H, et al. Opioids in the management of chronic non-cancer pain: an update of American Society of the Interventional Pain Physicians’ (ASIPP) Guidelines. Pain Physician 2008;11(2 Suppl):S5-S62.
  17. Opioid products chart: opioid products that may be required to have risk evaluation and mitigation strategies (REMS). FDA US Food and Drug Administration. Available at: Accessed August 10, 2011.
  18. Office of National Drug Control Policy. News release: new data reveal 400% increase in substance abuse treatment admissions for people abusing prescription drugs. July 15, 2010. Available at: Accessed August 10, 2011.
  19. Interagency guideline on opioid dosing for chronic non-cancer pain. Agency Medical Directors Group, Washington State. 2010 Update. Available at: Accessed August 10, 2011.