Overdose deaths linked to illicit "designer" benzodiazepines have surged in the United States, as underground labs crank out new synthetic variations on prescription tranquilizers like Valium, Xanax and Ativan.
Overdose deaths involving illicit benzos increased more than sixfold (520%) between 2019 and 2020, rising from 51 to 316, according to data from 32 states and the District of Columbia.
By comparison, fatal overdoses from prescription benzodiazepines rose 22%, from 921 to 1,122, according to a new report from Stephen Liu and colleagues at the U.S. Centers for Disease Control and Prevention.
These new designer drugs "are structurally similar to approved benzodiazepines, in the same drug class, but unfortunately these designer benzos have unknown clinical side effects and they have unknown toxicities," said Dr. Alex Manini. He's director of the Toxicology Research Core in the Emergency Medicine Research Division at Icahn School of Medicine at Mount Sinai, in New York City.
These illicitly manufactured drugs -- clonazolam, etizolam and flubromazolam -- are suspected to be more powerful than prescription benzodiazepines, increasing the risk of addiction and overdose, Manini said. Benzos typically are prescribed to treat anxiety disorders.
Their spread echoes previous U.S. experience with powerful synthetic opioids like fentanyl, experts said. As the opioid epidemic unfolded, users progressed from prescription opioids like OxyContin or Vicodin to cheaper and more powerful illicit substitutes.
"More synthetic benzodiazepines are being reported in toxicology reports across the globe, outpacing new synthetic opioids," said Pat Aussem, associate vice president of consumer clinical content development for the non-profit Partnership to End Addiction.
Ninety-three percent of benzodiazepine overdose deaths also involve opioids, according to data gathered during the first six months of 2020. Two-thirds of the time, illicit fentanyl was combined with a benzo.
Opioids and benzodiazepines both depress a person's breathing, and the combination is more likely to cause you to stop drawing breath, said Dr. Leigh Vinocur, a spokeswoman with the American College of Emergency Physicians.
"When you take them together, it definitely makes it worse and creates a bigger chance for overdose," Vinocur said.
Aussem noted that research suggests the combination "can raise the risk factor of an overdose by a factor of 10 as compared to prescribing opioids alone."
Using the two types of drugs together also makes it less likely that a person will respond to medications that can reverse an opioid overdose, Manini pointed out.
"The presence of opioids and benzodiazepines together, that's going to decrease the utility of our reversal agent, which is naloxone," he said. "If you're not able to reverse the drug overdose, that's a major problem."
Patients suffering such a combination overdose fail to respond to naloxone about one-third of the time, according to another study for which Manini served as senior author. It focused on illicit benzodiazepines.
Emergency room doctors often aren't even aware that benzos are playing a role in an overdose, Manini said.
"We weren't expecting to see benzodiazepines in these patients," he said. "A reversal agent does exist for benzodiazepines, but that's not typically given routinely, like naloxone is."
Unfortunately, people taking illicitly manufactured drugs bought off the street might not know that they've ingested an opioid/benzo combo, Aussem said.
"In terms of illicit drug use, adding benzodiazepines to opioids may reduce costs of drug suppliers and/or be used to enhance the euphoric effects of opioids," she said.
The emotional turmoil caused by the evolving COVID-19 pandemic likely has contributed to the continued increase in drug overdose deaths in the United States, said Dr. Teresa Amato, director of emergency medicine at Long Island Jewish Forest Hills in New York City.
"It is unclear as to what is affecting this increase, but there is concern that it may be an indirect effect of the isolation, anxiety and stress over the pandemic," Amato said.
And even though illicitly manufactured benzos are on the rise, Aussem said we shouldn't overlook the role that black-market prescription tranquilizers continue to play in overdoses and deaths.
"One example is a young woman who was asked by her drug supplier to make the case for a Xanax prescription with her health care provider even though she did not need it," Aussem said. "In return, she was promised prescription pain pills which she was misusing."
The studies were published in the Aug. 27 issue of the CDC's Morbidity and Mortality Weekly Report.
The American Association for Clinical Chemistry has more about designer benzodiazepines.
SOURCES: Alex Manini, MD, director, Toxicology Research Core, Emergency Medicine Research Division, Icahn School of Medicine at Mount Sinai, New York City; Pat Aussem, LPC, MAC, associate vice president, consumer clinical content development, Partnership to End Addiction, New York City; Leigh Vinocur, MD, spokeswoman, American College of Emergency Physicians; Teresa Amato, MD, director, emergency medicine, Long Island Jewish Forest Hills, Queens, N.Y; Morbidity and Mortality Weekly Report, Aug. 27, 2021