Vital Signs: Risk for Overdose from Methadone Used for Pain Relief — United States, 1999–2010

Leonard J. Paulozzi, MD; Karin A. Mack, PhD; Christopher M. Jones, PharmD


Morbidity and Mortality Weekly Report. 2012;61(26):493-497. 

In This Article

Abstract and Introduction


Background: Vital statistics data suggest that the opioid pain reliever (OPR) methadone is involved in one third of OPR-related overdose deaths, but it accounts for only a few percent of OPR prescriptions.
Methods: CDC analyzed rates of fatal methadone overdoses and sales nationally during 1999–2010 and rates of overdose death for methadone compared with rates for other major opioids in 13 states for 2009.
Results: Methadone overdose deaths and sales rates in the United States peaked in 2007. In 2010, methadone accounted for between 4.5% and 18.5% of the opioids distributed by state. Methadone was involved in 31.4% of OPR deaths in the 13 states. It accounted for 39.8% of single-drug OPR deaths. The overdose death rate for methadone was significantly greater than that for other OPR for multidrug and single-drug deaths.
Conclusions: Methadone remains a drug that contributes disproportionately to the excessive number of opioid pain reliever overdoses and associated medical and societal costs.
Implications for Public Health Practice: Health-care providers who choose to prescribe methadone should have substantial experience with its use and follow consensus guidelines for appropriate opioid prescribing. Providers should use methadone as an analgesic only for conditions where benefit outweighs risk to patients and society. Methadone and other extended-release opioids should not be used for mild pain, acute pain, "breakthrough" pain, or on an as-needed basis. For chronic noncancer pain, methadone should not be considered a drug of first choice by prescribers or insurers.


U.S. physicians have used the synthetic opioid methadone as a treatment for heroin addiction since the 1960s and increasingly as a treatment for chronic noncancer pain since the mid-1990s.[1] Individual states began to report increasing numbers of overdose deaths involving methadone in 2003.[2] Subsequently, rates of deaths and emergency department (ED) visits involving methadone have increased nationwide.[3,4] Studies using medical examiner data suggested that more than three quarters of methadone overdoses involved persons who were not enrolled in programs treating opioid addiction with methadone and that most persons who overdosed were using it without a prescription.[3] In November 2006, the Food and Drug Administration (FDA) issued a warning regarding careful prescribing of methadone because of the sharp rise in overdose deaths among patients receiving methadone for pain.[5] FDA also revised the interval for the recommended starting dosage from 2.5–10 mg every 3–4 hours to 2.5–10 mg every 8–12 hours. In January 2008, on request of the Drug Enforcement Administration (DEA), manufacturers voluntarily limited distribution of the largest (40 mg) formulation of methadone to authorized opioid addiction treatment programs and hospitals only, because this formulation was not approved for the treatment of pain.[6]

Recent analyses have shown that methadone was involved in one in three opioid-related deaths in 2008.[7] Moreover, the involvement of methadone in drug overdose deaths, in toxic exposures quantified by poison centers, and in diversion to nonpatients is disproportionate to the number of methadone prescriptions for pain when compared with other opioid pain relievers.[3,8] Analysis of ED data indicates that the estimated number of ED visits resulting from nonmedical use of methadone alone or in combination with other drugs in 2009 (n = 63,031) was significantly greater than the estimated number in 2004 (n = 36,806).[4] CDC reviewed national data on trends in methadone use and mortality and data from medical examiners on methadone mortality to determine whether additional recommendations for its safe use for pain treatment are necessary.


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