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Geographic Distribution of Opioid-Related Mortality in the Third-Wave Opioid Epidemic

Updated: Oct 16, 2022

By Mark Gold, MD

The opioid epidemic is a devastating public health crisis - over 47,600 overdose deaths in 2017 involved an opioid, and this number has seen a dramatic uptick in the last decade. Opioid-related mortality emerged as a public health issue in the 1990s,  which led to a common cultural understanding of the opioid epidemic as a rural issue (concentrated in the Midwest and Appalachia) caused by an increase in the prescription of oxycodone. Emerging research suggests that the narrative of the current crisis is not so simple - that in fact there are multiple co-occurring and distinct epidemics, characterized by different types of opioids as well as  geographical footprint.

This study, by Kiang, Basu, Chen, and Alexander, looked at the opioid overdose epidemic as multiple distinct subgroups, defined by the types of opioids driving mortality and the regions most affected. The first wave of the opioid epidemic, as recognized by the study, began in the mid-1990’s and was driven, in large part, by the increase in the prescribing of prescription opioids, the second wave began in 2010 when the nation saw a  dramatic increase in heroin-related deaths. The third and current wave, which began around 2013, is defined by the rapid increase of illicitly manufactured synthetic opioids as well as an expanded reach from rural to suburban areas.


  • The mean age at death was 39.8 years for men and was 43.5 years for women.

  • Opioid-related mortality rates, especially from synthetic opioids, rapidly increased in the eastern United States.

*In most states, mortality associated with natural and semisynthetic opioids (ie, prescription painkillers) remained stable.

*In contrast, 28 states had mortality rates from synthetic opioids that more than doubled every 2 years (ie, annual percent change, 41%).

+The District of Columbia had the fastest rate of increase in mortality from opioids, more than tripling every year since 2013.

+Eight states (Connecticut, Illinois, Indiana, Massachusetts, Maryland, Maine, New Hampshire, and Ohio) had opioid-related mortality rates that were at least doubling every three years, and two states (Florida and Pennsylvania) and Washington D.C. had opioid-related mortality rates that were at least doubling every two years.

+Among these 28 states, the mean mortality rate was 6.0 per 100 000 people.

*Most opioid-related deaths are occurring among young and middle-aged adults.

*This equates to a significant loss of life. Nationally, overall opioid-related mortality resulted in 0.36 years of life expectancy lost in 2016, which was 14% higher than deaths due to firearms and 18% higher than deaths due to motor vehicle crashes; 0.17 years of life expectancy lost was due specifically to synthetic opioids.

This study focused on the location of opioid-related deaths as well as their impact   on life expectancy, measured in years of Life Expectancy Lost (LEL). The findings complicate the dominant narrative—opioid-related deaths have increased two-fold every two years in 24 eastern states. The devastating loss is not confined to rural states or those with high rates of poverty. Due to the recent increase in mortality—mostly driven by synthetic opioids such as fentanyl—  LEL from opioids has surpassed firearms or car crashes.

What do These Results Tell Us?

The states with the greatest LEL in 2016 included West Virginia ,Ohio, Connecticut, Maryland, Massachusetts, Rhode Island, and Washington D.C.. This list runs counter to  pervasive, yet outdated narratives framing the current crisis as a rural issue that primarily affects low-income communities. This study helps substantiate a critical revision of the current narrative to account for the actual and growing impact of the overdose crisis.

Looking to the Future

State responses to the overdose epidemic have ranged from restricting the supply of prescription opioids to expanding access to treatment and the life-saving overdose reversal medication naloxone.  The authors suggest that recognizing and responding to the changing geographic trends of opioid-related mortality can empower states to enact more effective policies and better address the specific needs of their populations.

“Policies focused on reducing opioid-related deaths may need to prioritize synthetic opioids,” writes Kiang et al, and some states already have model policies that can serve as models to other states. There is recent evidence of decreases in some types of opioid-related mortality in Ohio, and the authors suggest that Ohio’s policy of increasing access to naloxone, implementing needle exchange programs, and increasing support for those with mental health and addiction problems can serve as a guide to other states as they start to address the rise in mortality in their own states.1

As eastern states move forward with thoughtful urgency in addressing opioid addiction and mortality in their states, it is imperative that they learn from the states who are modeling effective programming, but also that they look at the geographic reality of the opioid epidemic evolution across the eastern United States. The opioid epidemic has not evolved homogeneously across the United States. Focusing on the experience and needs of local populations, and the degree to which synthetic opioids are a driver of current mortality is key to creating effective policies and programming to reduce mortality.


In a cross-sectional study of 351,564 U.S. residents who died from opioid-related causes between 1999 and 2016, researchers analyzed opioid-related mortality rate and life expectancy lost at age 15 years by state and opioid type.

*A limitation of the study is the potential for misclassification of deaths, which could result in an underreporting of opioid-related deaths.


  1. Ahmad, F.B.,Rossen, L.M., Spencer, M.R.,Warner, M., Sutton, P. (2018). Provisional Drug Overdose Death Counts. Retrieved from Atlanta, GA; Centers for Disease Control

Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.


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