Study: Veterans Prescribed Opioids With Anti-Anxiety Medication Were at Higher Risk of Death

Rutgers Biomedical and Health Sciences Chancellor Brian Strom leads investigation of the effects of this combination.

Veterans who were simultaneously prescribed  opioids and benzodiazepines by the Veterans Health Administration (VHA) faced an increased risk of death, according to 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.

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.

Brian Strom

Chancellor, Rutgers Biomedical and Health Sciences

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.

“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 Rutgers Biomedical and Health Sciences Chancellor Brian Strom, chair of the committee that wrote the report.

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 (VA), which oversees VHA.

Death associated with prescribing both opioids and benzodiazepines has raised concerns among health care providers, federal agency officials, veterans and the public for decades.

Concerns about prescribing opioids and their interaction with benzodiazepines appeared in the clinical practice guidelines issued by the VA and the Department of Defense in 2010, as well as others in later years.

Members of the committee who released the report noted that in response to adverse outcomes, the VHA changed its clinical guidelines and policies – including during the years that the report examines.

Each year, about 9 million United States veterans receive health care services from the VHA, the health care system operated by the VA. 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 with 33% in 2012, similar to national trends. Between 2004 and 2009, 27% of these veterans also were 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 among veterans who were newly dispensed opioids when compared with veterans who were newly dispensed a nonopioid 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 with 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 with those who started at a lower dosage.
• There was an increased risk of death among veterans whose opioid dosages were escalated compared with those who were given a consistent dose.

Researchers involved with the report also analyzed how opioids and benzodiazepines affected suicide risk among veterans. While they cautioned the results were less conclusive than those in their examination of the risk of death from any cause, the researchers found that:

• There was an increased risk of death from suicide among veterans who were newly dispensed opioids compared with 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.
• Because of a lack of data, committee members were unable to analyze how different opioid dosage treatment strategies might have affected suicide.

The researchers only examined medical records for veterans treated by the VHA and didn’t compare outcomes between veterans treated by the VHA and those treated elsewhere. They also didn’t analyze illicit drug use. In addition, they noted their analysis examined only past events, and their findings aren’t intended to influence restriction for any medication nor to be viewed as an absolute contraindication for the clinical use of benzodiazepines with opioids.

The National Academies of Sciences, Engineering and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the U.S. to solve complex problems and inform public policy decisions.