Headlines about America’s worsening drug epidemic have focused on deaths from opioids—heroin and prescription painkillers such as OxyContin. But overdose deaths have also soared among the millions of Americans using benzodiazepine drugs, a class of sedatives that includes Xanax, Valium and Klonopin, according to a study led by researchers at Einstein, Montefiore Health System and the Perelman School of Medicine at the University of Pennsylvania. Their findings appeared in February in the American Journal of Public Health.

“We found that the death rate from overdoses involving benzodiazepines has increased more than fourfold since 1996—a public health problem that has gone under the radar,” says lead author Marcus A. Bachhuber, M.D., M.S., an assistant professor of medicine (general internal medicine) at Einstein and an attending physician in internal medicine at Montefiore. “Overdoses from benzodiazepines have increased at a much faster rate than prescriptions for the drugs, indicating that people have been taking them in a riskier way over time.”

An estimated one in 20 U.S. adults fills a benzodiazepine prescription during the course of a year. The drugs are prescribed for conditions including anxiety, mood disorders and insomnia.

In 2013, benzodiazepine overdoses accounted for 31 percent of the nearly 23,000 deaths from prescription drug overdoses in the United States. But little was known about the national trends in benzodiazepine prescribing or in fatalities from the drugs. To find out, the researchers examined data for the years 1996–2013 from two sources: the federally sponsored Medical Expenditure Panel Survey and multiple-cause-of-death data from the Centers for Disease Control and Prevention.

Their analysis revealed that the number of adults purchasing benzodiazepines by prescription increased by 67 percent over the 18-year period, from 8.1 million in 1996 to 13.5 million in 2013.

For those obtaining benzodiazepine prescriptions, the average quantity filled during the year more than doubled between 1996 and 2013. Crucially, the overdose death rate over the 18-year period increased from 0.58 deaths per 100,000 adults in 1996 to 3.14 deaths per 100,000 adults in 2013, a more than fourfold increase.

Overall, the rate of overdose deaths from benzodiazepines has leveled off since 2010. But for a few groups—adults ages 65 and over, blacks and Hispanics—the rate of overdose deaths after 2010 has continued to rise.

“The greater quantity of benzodiazepines prescribed to patients suggests a higher daily dose or more days of treatment, either of which could increase the risk of fatal overdose,” says senior author Joanna L. Starrels, M.D., M.S., an associate professor of medicine (general internal medicine) at Einstein and an attending physician in internal medicine at Montefiore.

Dr. Starrels also offers two other possible reasons for the spike in benzodiazepine deaths. “People at high risk for fatal overdose may be obtaining diverted benzodiazepines [i.e., not from medical providers], and we know that combining benzodiazepines with alcohol or drugs—including opioid painkillers—can lead to fatal overdoses,” she says. She notes that opioid prescribing has increased rapidly during most of the period covered in her study and that opioids are involved in 75 percent of overdose deaths involving benzodiazepines.