Rise in Overdose Deaths Driven by Drug Combinations

Jan. 4, 2024 –Experts are sounding the alarm that a combination of prescription and/or recreational drugs now contribute to nearly three-quarters of overdose deaths in the United States. 

Reports of the use of fentanyl along with the animal tranquilizer xylazine make preventing substance use disorder and associated overdose deaths even more complicated, experts said during a webinar sponsored by the National Institute for Health Care Management. 

“Nearly 74% of all overdose deaths linked to cocaine now involve synthetic opioids, such as fentanyl,” said Cecelia Spitznas, PhD, a senior science policy analyst in the White House Office of National Drug Control Policy. “This type of combination drug use is part of a new trend driving the overdose rate, along with a growing use of xylazine, or ‘tranq.’” 

The White House declared the drug combinations as an emerging threat against the United States in April. 

In terms of overdose prevention, “if you yourself use any substance or if you know anybody who uses substances, here’s a couple of things that we like to encourage people to think about,” Shawn Westfahl, overdose prevention and harm reduction coordinator at Prevention Point Philadelphia, said during the webinar. Avoid using drugs alone. “Most people who die from opioid overdose die with nobody around them. We encourage people to use the buddy system and stagger their use.”

Westfahl also suggests that people using substances “go slow, go easy, especially if they inject. They can put more in; they can’t take it out. And we encourage people to avoid mixing in other drugs with opioids.”

Medically Assisted Treatment

Although equal access is a challenge, “the most important thing that we in the United States can do at this point in time to combat the substance use disorders epidemic, and that’s increasing access to evidence-based treatment, in particular … to medically assisted treatment,” said Doug Henry, PhD, vice president of psychiatry and behavioral health at Allegheny Health Network in Pittsburgh. 

Allegheny Health launched a program in 2020, for example, to increase access in medically assisted treatment in rural and underserved areas in West Virginia. Offering remote treatment “was really groundbreaking,” Henry said, especially in regions with certain geographic and population density challenges.

Getting people engaged in medically assisted treatment, and keeping them in treatment, “is hugely, hugely important,” Henry said. “These efforts have led to a reduction in opioid-related overdoses.” 

What’s Alarming the Experts

Henry agreed that drug combinations are adding to the challenge.

“The ongoing opioid epidemic and the emerging epidemic of combined molecules into deadly poisons are leading to an increased frequency of overdoses,” he said. He is seeing spikes in both of his professional roles – at Allegheny Health, a 14-hospital network in southwestern Pennsylvania and western New York, and at Highmark Health, the third largest Blue Cross Blue Shield insurance company in the United States, serving members primarily in West Virginia, western New York, Delaware, and Pennsylvania. 

Westfahl reported that 1,413 people died from drug overdoses in 2022 in Philadelphia, up from 1,276 overdose deaths in 2021, a 10% increase. Most of the 2022 deaths, 83%, involved opioids. Fentanyl and tranq remain major challenges for the population served by Prevention Point, he said. 

“We are seeing a huge spike [in fentanyl use] consistently increasing throughout the years,” he said.

In 2010, for example, fentanyl was involved in fewer than 10% of drug overdoses. Last year, fentanyl played a role in 96% of overdose deaths. 

The national picture is not much more encouraging, Spitznas said. About 25%, or 70 million Americans, used illicit drugs in 2022, national survey data reveal. More than 17%, or nearly 49 million Americans, reported past-year substance use disorder.

Marijuana led drug use among Americans 12 years and older. An estimated 62 million Americans used marijuana in 2022. Next, two of the most common drugs used are in categories such as hallucinogens and pain reliever misuse, each involving 8.5 million Americans. Also, nearly 5 million people misused prescription tranquilizers and sedatives.

In terms of deaths, there’s been a dramatic uptick blamed on synthetic opioids and fentanyl, climbing to just under 80,000 deaths in April 2023. Spitznas said the categories are not mutually exclusive because many drugs are used in combination. In addition, “we think both the heroin figure and the fentanyl figures are dramatic undercounts” in national surveys. 

“Fentanyl is often used in to contaminate certain substances, so it’s unlikely that people really, truly know if they are using heroin or they’re using fentanyl,” she said. Fentanyl and xylazine test strips, if available, can help determine what substances are present when someone is overdosing. 

Good and Bad News on Treatment

National data also shows that only about 24% of Americans 12 years and older who are classified as needing substance use treatment receive it. A silver lining can be seen in a breakdown by age group, Spitznas said. “We’re doing a little bit better in getting 12- to 17-year-olds in treatments.”

Compared to the 25% of younger teens receiving treatment, “we’re doing really poorly in getting 18- to 25-year-olds into treatment,” she said. The figure is a little more than 16%. “And across the board, we need to get more people into treatment.”

Providing naloxone is a priority, Spitznas said. The FDA approved the first over-the-counter nasal naloxone spray in March. The agency also approved a second agent to reverse opioid overdoses called nalmefene in May.

If a person is overdosing on both fentanyl and tranq, the opioid reversal agents can treat the effects of fentanyl. But xylazine, or tranq, is not an opioid. It’s a veterinary medicine that causes prolonged sedation, and the FDA has not approved its use in humans. 

“One way to think about this is that naloxone can restore breathing. You may not have a rapid return of consciousness when there’s fentanyl and xylazine together. But as long as breathing returns, that is a good thing,” Spitznas said. “That is why we’re recommending continuing with naloxone as well as calling 911 and getting emergency services.”

Treatment for combination overdoses may not ease withdrawal symptoms. “People dependent on xylazine may experience an extreme withdrawal, even if they receive medications for opioid use disorder,” Spitznas said. There is no medication available for xylazine withdrawal, she said. 

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