WASHINGTON — Veterans who were prescribed an opioid and a benzodiazepine at the same time by the Veterans Health Administration (VHA) faced an increased risk of death, says a new report from the National Academies of Sciences, Engineering, and Medicine that analyzed millions of VHA medical records from 2007 to 2019. The report also finds some evidence that co-prescribing opioids and benzodiazepines increased veterans’ risk of death from suicide.  

Death associated with co-prescribing opioids and benzodiazepines has raised concerns among health care providers, federal agencies, veterans, and the public for decades. Opioids are commonly prescribed for pain, and benzodiazepines are often prescribed for anxiety, panic disorders, insomnia, and seizures. The combination of taking both drugs at the same time is known to have potential adverse health effects, including suppressing breathing.  

Concerns about prescribing opioids and their interaction with benzodiazepines first appeared in the VA/DOD Clinical Practice Guidelines in 2010. The report notes that in response to adverse outcomes, the VHA changed its clinical guidelines and policies – including during the years that the report examines.  

“Our report adds an important point of confirmation to the ongoing conversation on how past opioid and benzodiazepine prescribing practices affected veterans seeking treatment for pain, as well as conditions like post-traumatic stress disorder, anxiety, and depression,” said Brian Strom, chair of the committee that wrote the report, chancellor of Rutgers Health, and executive vice president for health affairs at Rutgers University.  

Each year about 9 million U.S. veterans receive health care services from the VHA. Veterans who receive health care through the VHA have a higher prevalence of both physical and mental health conditions such as post-traumatic stress disorder, anxiety, and depression compared with veterans who are treated elsewhere in the U.S. health care system. Studies have shown that about 19% of all veterans being treated at the VHA in 2004 were receiving an opioid prescription, compared to 33% in 2012, similar to national trends. Between 2004 and 2009, 27% of these veterans were also prescribed benzodiazepines. Opioid prescriptions declined overall at the VHA starting in 2012.  

The report concludes that among veterans who received care from the VHA between 2007 and 2019:

• There was an increased risk of death (all-cause mortality) among veterans who were newly dispensed opioids, when compared with veterans who were newly dispensed a non-opioid alternative drug to treat pain.

• There was an increased risk of death among veterans who were prescribed both opioids and benzodiazepines. This was true both when compared to veterans who were prescribed a benzodiazepine and an alternative to opioids, as well as to veterans who were prescribed an opioid and an alternative to benzodiazepines.

• There was an increased risk of death among veterans who started opioid treatment at a higher dosage, compared to those who started at a lower dosage.

• There was an increased risk of death among veterans whose opioid dosages were escalated compared to those who were given a consistent dose.

• There was an increased risk of death (all-cause mortality) among veterans who were newly dispensed opioids, when compared with veterans who were newly dispensed a non-opioid alternative drug to treat pain.

• There was an increased risk of death among veterans who were prescribed both opioids and benzodiazepines. This was true both when compared to veterans who were prescribed a benzodiazepine and an alternative to opioids, as well as to veterans who were prescribed an opioid and an alternative to benzodiazepines.

• There was an increased risk of death among veterans who started opioid treatment at a higher dosage, compared to those who started at a lower dosage.

• There was an increased risk of death among veterans whose opioid dosages were escalated compared to those who were given a consistent dose.

The report also analyzes how opioids and benzodiazepines affected suicide risk among veterans. While the report cautions that the results were less conclusive than those in its examination of the risk of death from any cause, it finds:

• There was an increased risk of death from suicide among veterans who were newly dispensed opioids compared to those newly dispensed an opioid alternative.

• There is no evidence of a difference in the risk of death from suicide among veterans taking a benzodiazepine who were newly dispensed opioids compared with those who were newly dispensed an opioid alternative.

• There was some evidence of a higher risk of death from suicide among veterans co-prescribed opioids and benzodiazepines, although the estimate is imprecise at three months after dispensing begins.

• Due to a lack of data, the committee was unable to analyze how different opioid dosage treatment strategies might have affected suicide.

• There was an increased risk of death from suicide among veterans who were newly dispensed opioids compared to those newly dispensed an opioid alternative.

• There is no evidence of a difference in the risk of death from suicide among veterans taking a benzodiazepine who were newly dispensed opioids compared with those who were newly dispensed an opioid alternative.

• There was some evidence of a higher risk of death from suicide among veterans co-prescribed opioids and benzodiazepines, although the estimate is imprecise at three months after dispensing begins.

• Due to a lack of data, the committee was unable to analyze how different opioid dosage treatment strategies might have affected suicide.

The new report only examines medical records for veterans treated by the VHA, and does not compare outcomes between veterans treated by the VHA and those treated elsewhere. The report also does not analyze illicit drug use. The report also notes that its analysis examined only past events, and is not intended to influence restriction for any medication nor to be viewed as an absolute contraindication for the clinical use of benzodiazepines with opioids.  

The study — undertaken by the Committee on Evaluating the Effects of Opioids and Benzodiazepines on All-Cause Mortality in Veterans — was sponsored by the U.S. Department of Veterans Affairs. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, engineering, and medicine. They operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln.

Contact:

Megan Lowry, Media Relations Manager
Office of News and Public Information
202-334-2138; email news@nas.edu