Methadone safety: A clinical practice guideline from the american pain society and college on problems of drug dependence, in collaboration with the heart rhythm society

Roger Chou, Ricardo A. Cruciani, David A. Fiellin, Peggy Compton, John T. Farrar, Mark C. Haigney, Charles Inturrisi, John R. Knight, Shirley Otis-Green, Steven M. Marcus, Davendra Mehta, Marjorie C. Meyer, Russell Portenoy, Seddon Savage, Eric Strain, Sharon Walsh, Lonnie Zeltzer

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195 Scopus citations


Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence. Perspective This guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias.

Original languageEnglish
Pages (from-to)321-337
Number of pages17
JournalJournal of Pain
Issue number4
StatePublished - Apr 2014

Bibliographical note

Funding Information:
List of Panel Members With Conflicts of Interest Disclosure C onflicts of I nterest D isclosed Cochairs APS: Ricardo Cruciani, MD Received speaking fees from Depomed Advisory Board and Speaker Bureau; Covidean Speaker Bureau; ENDO Pharmaceuticals Speaker Bureau; Ameritox consultant; grant support; Grupo Ferrer consultant (Spain). Received research funding from Ameritrox, New York State. CPDD: David A. Fiellin, MD Received honoraria for serving on external advisory panels monitoring the abuse and diversion of buprenorphine for Pinney Associates and Parajuarx. Panel members Roger Chou, MD No conflicts disclosed. Peggy Compton, RN, PhD No conflicts disclosed. John T. Farrar, MD, PhD Dr. Farrar has received research grant support (through the University of Pennsylvania) and consulting fees from Purdue Pharma, Forrest Pharma, Endo Pharma, Cephalon Inc, and currently from Teva Pharma. Mark C. Haigney, MD No conflicts disclosed. Charles Inturrisi, PhD No conflicts disclosed. John R. Knight, MD No conflicts disclosed. Shirley Otis-Green, MSW, ASW No conflicts disclosed. Steven M. Marcus, MD No conflicts disclosed Davendra Mehta, MD Consulting fee from St. Jude's and speaker fee from Sanofi. Marjorie C. Meyer, MD No conflicts disclosed. Russell Portenoy, MD Honorarium received from Spanish company, Grupo Ferrer for teaching conference; honorarium from Pfizer for consulting. Conducts research on the Nabiximols project funded by Otsuka, Inc. Seddon Savage, MD, MS No conflicts disclosed. Eric Strain, MD Employed as medical director of a clinic that treats patients with opioid use disorders and patients with pain. Consulting for: Transcept Pharmaceuticals, Inc; The Oak Group; and Salfix Pharmaceuticals, Inc. Received National Institutes of Health funding; may receive in next 1 to 2 years pharmaceutical funding for opioid research. Sharon Walsh, PhD Received research support from World Meds, Inc, and Catalyst Pharmaceuticals. Served as a paid consultant on abuse liability assessment research and medications development to pharmaceutical companies, including affiliations with Abbot Laboratories, Meda Pharmaceuticals, and Yaupon Pharmaceuticals. Received honoraria and travel support as an invited speaker for Reckitt-Benckiser. Lonnie Zeltzer, MD Chair of data-monitoring committee (DMC) for buprenorphine study in children; Purdue Pharma, paid for initial take-off meeting and travel reimbursement, but no patients have completed the study yet and so no DMC reports yet. Received honoraria for lectures on chronic pain and integrative medicine in individuals with Fabry, Pompe, or Gaucher's disease sponsored by Sanofi, Inc.


  • Clinical practice guideline
  • chronic pain
  • methadone
  • opioid addiction
  • safety

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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