Although the U.S. may have passed the peak in use and abuse of prescription opioids (pain medications), recent studies show no decline in the co-prescribing of opioid pain medications and sedatives whose interaction can slow breathing and dramatically raise the risk of overdose death.

"Multidrug use is the trailing edge of the opioid epidemic," said Mark Sullivan, M.D., Ph.D, a UW professor of psychiatry and behavioral sciences and the executive director of COPE for Chronic Pain CME at the UW School of Medicine. "We are making progress on decreasing opioid prescribing, but co-prescribing of opioids and sedatives has not decreased."

This is important, he says, because most prescription opioid deaths commonly involve alcohol, sedatives, and/or illicit drugs such as heroin. But the most fatal combination is opioids and common benzodiazepines, which are medications prescribed for depression, anxiety and sleep. A leading pain research specialist, Sullivan provided commentary, "What are we treating with opioid and sedative-hypnotic combination therapy?" in the journal Pharmacoepidemiology and Drug Safety.

It is estimated that as much as 80 percent of unintentional overdose deaths related to opioids may involve benzodiazepines. Prescription opioids, benzodiazepines and muscle relaxants are all central nervous system depressants, and their combination can slow breathing to the point of death. According to the Centers for Disease Control and Prevention, in 2013 over 16,000 people in the US died from overdoses involving opioid painkillers and 6,973 died from overdoses involving benzodiazepines.

The extent that opioids and sedatives are co-prescribed is detailed in new research by Marc LaRochelle, M.D., at the Boston University School of Medicine, and colleagues, published in the same issue of the journal. The authors found that prescribing of benzodiazepines is three to four times more likely when opioids are prescribed. Their review of more than 30,000 patient visits for during 2001-2010 found that when these patients were prescribed opioids for acute musculoskeletal pain, 33 percent also received a prescription for a sedative. Among patients who were prescribed opioids for chronic musculoskeletal pain, 36 percent of patients also received a prescription for a sedative. Persons with psychiatric and substance abuse disorders were more likely to be co-prescribed high-dose opioids and sedatives. For example veterans with PTSD were more likely to be co-prescribed opioids and sedatives than veterans without PTSD.

"Patients who are on long-term combined opioid and benzodiazepine therapy are often on a treadmill," Sullivan said. "They feel relief when they take their medications and withdrawal when they stop, so they continue this combined therapy, even though many function poorly and some will die as a result."

Sullivan points out that solutions include improved prescriber education to help clinicians better understand the risks and benefits associated with prescription opioids. He notes it is crucial to adopt more effective and integrated approaches to treating patients with chronic pain, and improve access to, and insurance coverage for, evidence-based substance abuse treatment, including medication-assisted treatment for opioid use disorders with buprenorphine and other medications.

This approach to treating chronic pain is detailed in the recently released 2015 Washington State Interagency Guideline on Prescribing Opioids for Pain. Sullivan was a contributor to these guidelines and directs the COPE for Chronic Pain CME Program (, which offers free continuing medical education on safe opioid prescribing and effective treatment of chronic pain.