TY - JOUR
T1 - Methadone overdose and cardiac arrhythmia potential
T2 - Findings from a review of the evidence for an american pain society and college on problems of drug dependence clinical practice guideline
AU - Chou, Roger
AU - Weimer, Melissa B.
AU - Dana, Tracy
N1 - Funding Information:
Supported by the American Pain Society. M.B.W.'s time was partially supported by the Samuel F. Wise Trust.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
KW - Methadone
KW - evidence-based medicine
KW - harms
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=84897386210&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897386210&partnerID=8YFLogxK
U2 - 10.1016/j.jpain.2014.01.495
DO - 10.1016/j.jpain.2014.01.495
M3 - Article
C2 - 24685459
AN - SCOPUS:84897386210
SN - 1526-5900
VL - 15
SP - 338
EP - 365
JO - Journal of Pain
JF - Journal of Pain
IS - 4
ER -