Abstract
The number of deaths associated with methadone use increased dramatically in parallel
with marked increases in its use, particularly for treatment of chronic pain. To develop
a clinical guideline on methadone prescribing to reduce potential harms, the American
Pain Society commissioned a review of various aspects related to methadone safety.
This article summarizes evidence related to unintentional overdose due to methadone
and harms related to cardiac arrhythmia potential. We searched Ovid MEDLINE, the Cochrane
Library, and PsycINFO databases through January 2014 for studies assessing harms associated
with methadone use; we judged 70 studies to be relevant and to meet inclusion criteria.
The majority of studies on overdose and cardiac arrhythmia risk are observational
and provide weak evidence on which to base clinical guidelines. In patients prescribed
methadone for treatment of opioid dependence, data suggest that mortality benefits
related to reduction in illicit drug use outweigh harms. Despite epidemiologic data
showing marked increases in the numbers of methadone-related deaths that have been
primarily attributed to increased use of methadone for chronic pain, evidence on methadone
and mortality risk in this population has been somewhat contradictory. There is some
evidence that recent initiation of methadone, psychiatric admissions, and concomitant
use of benzodiazepines are associated with a higher risk for overdose. Evidence on
cardiac risks is primarily limited to case reports of torsades de pointes, primarily
in patients on high doses of methadone, and to studies showing an association between
methadone use and prolongation of QTc intervals. Research is needed to understand
the effectiveness of dosing methods, electrocardiogram monitoring, and other risk
mitigation strategies in patients prescribed methadone.
Perspective
This systematic review synthesizes the evidence related to methadone use and risk
for overdose and cardiac arrhythmia. Findings regarding the association between methadone
use and QTc interval prolongation and risk factors for methadone-associated overdose
suggest potential targets for risk mitigation strategies, though research is needed
to determine the effectiveness of such strategies at reducing adverse outcomes.
Key words
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Article info
Footnotes
Supported by the American Pain Society. M.B.W.'s time was partially supported by the Samuel F. Wise Trust.
The authors report no conflicts of interest.
Dear Reader,
The development of guidelines is a complex and costly enterprise. Funding is increasingly reliant on providing impact and outcome data. The American Pain Society requests your assistance in evaluating the impact of the Methadone Safety Guideline. Please follow this link (http://www.surveygizmo.com/s3/1548754/APS-Methadone-Survey) to complete a brief questionnaire before reading the guideline. The survey consists of 11 multiple-choice questions and should take no more than a few minutes.
We also seek readers willing to take a follow-up survey (see instructions at the end of this survey). These data will assist the APS in developing data on guideline impact and thus assist us in securing and determining allocation of funding in the future. We are offering a token incentive for your participation.
Thank you for your cooperation.
Clinical Practice Guidelines Committee
American Pain Society
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© 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
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- Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm SocietyThe Journal of PainVol. 15Issue 4
- PreviewMethadone 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.
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- PreviewMethadone-associated overdose deaths have dramatically increased. In order to inform an evidence-based clinical practice guideline to improve safety of methadone prescribing, the American Pain Society commissioned a systematic review on various aspects related to methadone safety. We searched Ovid MEDLINE, Cochrane Library, and PsycINFO databases through July 2012 to identify studies that addressed 1 or more of 17 Key Questions related to methadone safety; an update search was performed in 2014 for new studies related to methadone-related overdose and risks related to cardiac arrhythmias.
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