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Drug overdose death rates involving fentanyl, methamphetamine, and cocaine increased from 2016 through 2021, CDC researchers said.

The age-adjusted overdose death rate involving fentanyl rose by 279%, from 5.7 per 100,000 standard population in 2016 to 21.6 per 100,000 in 2021, reported Merianne Rose Spencer, MPH, an epidemiologist in the Division of Analysis and Epidemiology at the CDC's National Center for Health Statistics, and colleagues.

Rates of overdose deaths involving methamphetamine more than quadrupled, from 2.1 per 100,000 in 2016 to 9.6 in 2021, and those involving cocaine more than doubled, from 3.5 to 7.9, respectively, they noted in .

In contrast, rates of overdose deaths that involved heroin fell by 40.8%, from 4.9 to 2.9 per 100,000, and rates of overdoses involving oxycodone dropped by 21%, from 1.9 to 1.5.

"Drug overdose deaths continue to be a significant public health burden in the United States, given the rise in rates over the past 2 decades," Spencer and team noted. "This report presents the trend in drug overdose deaths for the five most frequent opioids and stimulant drugs involved in deaths in the United States from 2016 through 2021."

Across all five of the drugs studied, overdose death rates were higher for males than females per 100,000:

• Fentanyl: 31.3 vs 11.9
• Methamphetamine: 13.8 vs 5.4
• Cocaine: 11.3 vs 4.5
• Heroin: 4.2 vs 1.5
• Oxycodone: 1.7 vs 1.3

In 2021, among adults ages 25-34 and 35-44, overdose death rates were highest for fentanyl (40.8 and 43.5, respectively), followed by methamphetamine (15.4 and 20.3) and cocaine (11.5 and 14.9).

For those ages 45-54 and 55-64, the rate of overdose deaths was similar for deaths involving fentanyl, cocaine, and methamphetamine, though were highest with fentanyl (32.7 and 24.8, respectively).

Among those ages 0-24 and 65 and over, the overdose death rate involving fentanyl was higher than other drug types, but it was "not significantly different," Spencer and co-authors noted.

Looking at race and ethnicity, fentanyl was the number one drug tied to overdose deaths in 2021, with age-adjusted rates of 31.3 for Black people, 24.6 for white people, 33.1 for American Indian or Alaska Native people, 14.1 for Hispanic people, and 2.3 for Asian people.

Finally, the authors also observed geographic differences. In 2021, overdose death rates that involved fentanyl were highest across all regions with the exception of two: Region 8 (Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming) and Region 10 (Alaska, Idaho, Oregon, and Washington), where death rates involving fentanyl and methamphetamine "were similar," Spencer and team noted.

The regions in which drug overdose death rates involving fentanyl were highest were Region 1 (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) and Region 3 (Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia), at 32.2 and 32.0, respectively.

For this study, Spencer and colleagues analyzed "literal text" -- consisting of information documented by medical certifiers, typically medical examiners or coroners, that "describe the causes, manner, and circumstances contributing to the death" -- from National Vital Statistics System mortality data for deaths occurring among U.S. citizens in the U.S.

The authors noted that the "quality and completeness of the information provided" in the literal text of the death certificates can vary across different jurisdictions due to differences in the ways deaths are reported.

"Variations in the way drug overdose deaths are reported on death certificates, including the level of detail on specific drugs involved, can impact comparability," they wrote. In addition, reporting of deaths involving at least one particular drug improved from 2016 to 2021, they said.

"These improvements in specificity could affect the magnitude and distribution of deaths due to specific drugs," they added. However, they also cited a previous study that adjusted for enhanced reporting practices and still found similar patterns when comparing the observed rates and adjusted rates.

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