US opioid overdose epidemic and the fentanyl wave

CDC describes the epidemic as three waves. The first, from 1999, followed a rise in opioid prescribing during the 1990s. The second, from 2010, brought rapid increases in deaths involving heroin. The third, from 2013, was driven by synthetic opioids, above all illegally made fentanyl, sold as powder or pressed into counterfeit pills. Between 1999 and 2014 more than 165,000 people died of overdoses involving prescription opioid pain medicines.

On 17 November 2021 the National Center for Health Statistics reported an estimated 100,306 overdose deaths in the 12 months ending April 2021, up 28.5 percent from 78,056 a year earlier. Deaths involving opioids rose from 56,064 to 75,673, and deaths involving synthetic opioids, mainly fentanyl, kept climbing. The final count for calendar 2021 was 106,699 deaths, an age-adjusted rate of 32.4 per 100,000.

That rate had been 6.8 per 100,000 in 2001. By 2021 the death rate involving synthetic opioids other than methadone, a group that includes fentanyl, was 21.8 per 100,000. Between 2020 and 2021 alone the synthetic opioid rate rose another 22 percent while the heroin death rate fell 32 percent. CDC now reports that illegally made fentanyl has largely saturated the illegal drug supply and can have other drugs mixed into it. By CDC's count about 806,000 people died of opioid overdoses from 1999 through 2023.

The toll then fell. In May 2025 NCHS estimated 80,391 overdose deaths for 2024, 26.9 percent fewer than the 110,037 of 2023 and the lowest annual figure since 2019. Deaths involving opioids dropped from an estimated 83,140 to 54,743.