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Synthetic Opioid Overdose Data

Excluding methadone but including drugs like tramadol and fentanyl—prescribed fentanyl and illicitly manufactured fentanyl.

The death rate of synthetic opioids other than methadone, which includes drugs such as tramadol and fentanyl, increased by 100.0% from 2015 to 2016.1

Synthetic opioid death rates (other than methadone) increased across all demographics, regions, and numerous states. State reports have indicated that increases in synthetic opioid-involved deaths have been associated with the number of drug products obtained by law enforcement that test positive for fentanyl but not fentanyl prescribing rates. These reports indicate that increases in synthetic opioid-involved deaths are being driven by increases in fentanyl-involved overdose deaths, which are likely the result of illicitly-manufactured fentanyl.2,3,4


Synthetic Opioid-Related Overdose Deaths

Death rates involving synthetic opioids doubled from 2015 to 2016. This data confirms that increases in drug overdose deaths are being driven by continued sharp increases in deaths involving synthetic opioids (other than methadone), such as illicitly manufactured fentanyl (IMF).

  • In 2016, there were more than 19,000 deaths relating to synthetic opioids (other than methadone) in the United States.
  • Also in 2016, the largest increases in overdose death rate from synthetic opioids were in persons aged 25-44, specifically males 25-44.
  • Synthetic opioid overdose deaths significantly increased in 21 states, with 10 states at least doubling their rates in 2016. New Hampshire, West Virginia, and Massachusetts had the highest death rates from synthetic opioids.1

What is Fentanyl?

Fentanyl is a synthetic (man-made) opioid 50x more potent than heroin and 100x more potent than morphine. There are two types of fentanyl:

  • Pharmaceutical fentanyl is primarily prescribed to manage severe pain, such as with cancer and end-of-life palliative care.
  • Non-pharmaceutical fentanyl is frequently referred to as illicitly manufactured fentanyl (IMF). IMF is often mixed with heroin and/or cocaine—with or without the user’s knowledge—in order to increase the drug’s effect.


There are also fentanyl analogs, such as acetylfentanyl, furanylfentanyl, and carfentanil, which are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Carfentanil, is estimated to be 10,000 times more potent than morphine. 5

  • Large central metro—Counties in metropolitan statistical areas of 1 million or more population that:
    • Contain the entire population of the largest principal city
    • Have their entire population contained in the largest principal city
    • Contain at least 250,000 inhabitants of any principal city
  • Large fringe metro—Counties of 1 million or more population that did not qualify as large central metro counties.
  • Medium metro—Counties of populations of 250,000 to 999,999.
  • Small metro—Counties of populations less than 250,000.
  • Micropolitan—Counties in micropolitan statistical areas that have a population of at least 10,000 but less than 50,000.
  • Noncore—Nonmetropolitan counties that did not qualify as micropolitan.


Categories of 2013 NCHS Urban-Rural Classification Scheme for Counties (


Age-adjusted death rates for synthetic opioids are plotted above by urbanization classification of residence for 2015 to 2016. Rates increased significantly for all areas – large central metro (141.7%), large fringe metro (110.3%), and medium metro (80.0%), small metro (88.0%), micropolitan (66.7%), and noncore (57.7%) areas. The synthetic opioid overdose death rate also increased in the United States overall—a statistically significant 100.0% increase from 2015 to 2016, with a total of 19,413 deaths in 2016. Deaths are classified using the International Classification of Diseases, Tenth Revision (ICD–10). Drug overdose deaths are identified using underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Drug overdose deaths, as defined, that have synthetic opioids other than methadone (T40.4) as a contributing cause. Age-adjusted death rates were calculated using the direct method and the 2000 standard population.1



  1. Seth P, Scholl L, Rudd RA, Bacon S. Increases and Geographic Variations in Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants with Abuse Potential – United States, 2015-2016. MMWR Morb Mortal Wkly Rep. ePub: 29 March 2018.
  2. Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions and increases in synthetic opioid-Involved overdose deaths – 27 states, 2013-2014. Morb Mortal Wkly Rep. 2016;65(33):837-43.
  3. Peterson AB, Gladden RM, Delcher C, Spies E, Garcia-Williams A, Wang Y, et al. Increases in fentanyl-related overdose deaths – Florida and Ohio, 2013-2015. Morb Mortal Wkly Rep. 2016;65(33):844-9.
  4. O’Donnell JK, Gladden RM, Seth P. Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region — United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017;66:897–903.
  5. O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. MMWR Morb Mortal Wkly Rep 2017;66:1197–1202.