The mixing of opioid medications and benzodiazepines has been found by the National Institutes of Health to be a significant factor in opioid overdose deaths. But a new study suggests that co-prescriptions of benzodiazepines and opioids in the US are on the decline.
Benzodiazepines, such as as lorazepam and diazepam, are typically prescribed as a sleep aid and to treat anxiety. Opioids, such as morphine and oxycodone, are typically prescribed for pain relief, according to the National Institute on Drug Abuse.
People taking opioids and benzodiazepines together are far more likely to overdose
Benzodiazepines are typically prescribed as a sleep aid and to treat anxiety
New opioid prescriptions for those taking benzodiazepines halved from 2010 to 2015
Patients are prescribed both types of drugs to combine the sedative and anti-anxiety effects of one with the painkilling effects of the other -- particularly for those with chronic pain. Both types of drugs are reportedly over-prescribed in the US, according to a 2016 study.
The new study, which published Thursday in JAMA Psychiatry, compared new opioid prescriptions nationwide between patients taking benzodiazepines and those who are not. The researchers found that, in 2015, those patients taking benzodiazepines were more than twice as likely to be prescribed opioids compared to those not taking benzodiazepines.
This is a drop from 2010, when those taking benzodiazepines were nearly four times as likely to be prescribed opioids, according to the study.
"We focused on new prescriptions, and that's not something that most studies have done," said Dr. Joseph Ladapo, an internal medicine physician at Ronald Reagan UCLA Medical Center in Los Angeles and a leading author on the study. "And new prescriptions are key because once you start [taking opioids], you have to consider how you're going to stop it and how you're going to manage it."
Previous research has suggested that people who are prescribed both benzodiazepines and opioids are four to ten times more likely to overdose compared to those who are prescribed opioids alone. According to the National Institute on Drug Abuse, more than 30% of opioid overdose cases also involve benzodiazepines.
The reason the interaction between opioids and benzodiazepines is so dangerous is that they have a combined effect on breathing. Specifically, both benzodiazepines and opioids slow down the central nervous system, including the respiratory drive that keeps us alive, according to the National Institute on Drug Abuse.
Consequently, using the two types of drugs together can lead to respiratory depression, coma and death, according to Nabarun Dasgupta, a senior epidemiologist at the Gillings School of Global Health at the University of North Carolina at Chapel Hill, who was not involved in the most recent study.
"People need to be aware that if they're taking a benzodiazepine -- and a lot of patients are taking benzodiazepines -- and they're also prescribed an opioid, their risk of overdosing is much higher," Ladapo said.
"Our work shows that these patients [taking benzodiazepines], not only are they at higher risk of accidentally overdosing, but they are also more likely to be prescribed opioids. So they're higher risk and they're more likely to be exposed to the opioids in the first place."
In the study, the researchers used data from the 2005-2015 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey to identify 13,146 new opioid prescriptions among adults 20 years and older. For those taking benzodiazepines, the rate of new opioid prescriptions nearly doubled between 2005 and 2010 but then dropped to 2005 levels by 2015.
This suggests that the peak of co-prescribing occured around 2010. The reason for the subsequent drop in co-prescribing is unclear, but increased coverage of the opioid epidemic due in part to celebrity overdoses may have played a role, according to Ladapo.
"Overall, there was a decline in opioid prescribing around that time. I think it was around the time that Michael Jackson overdosed ... and celebrity-related events can sometimes cause these more rapid changes in what patients are doing," Ladapo said.
The results of the study were also stratified by ethnicity, gender, age and pain diagnosis. Those patients taking benzodiazepines who were at highest risk for a new opioid prescription included African-Americans, Hispanics, those diagnosed with headaches or musculoskeletal pain, and those between 20 and 39 years of age, according to Ladapo.
The new study comes nearly one week after Surgeon General Vice Admiral Dr. Jerome Adams released an advisory recommending that opioid users and community members familiarize themselves with naloxone, a medication used to treat opioid overdose. In the advisory, the surgeon general warned of an increased risk of accidental overdose for those taking "sedating medications, such as benzodiazepines (anxiety or sleep medications)."
This is not the first time that an overlap between opioid and benzodiazepine prescriptions has been identified. A 2016 study found that 80% of all people prescribed opioids in the state of North Carolina had also been prescribed a benzodiazepine in the previous year.
"It's a shocking number and it's been repeated in other studies, too," Dasgupta said. "It's a fairly common practice and I think that makes this question so interesting."
"We know that benzodiazepines and opioids can suppress your breathing," Dasgupta said. "On the other hand, we have all these physicians who have been prescribing opioids and benzos together for years to tens of millions of patients ... [and] maybe don't perceive this to be as big a risk."
In 2016, the US Food and Drug Administration issued "black-box warnings" on nearly 400 products to warn about the dangers of using benzodiazepines in combination with opioids.
The researchers of the study were not able to look at specific medication dosages, one of the study's main limitations, according to Ladapo.
But the study still suggests that co-prescription patterns in the US may be moving in the right direction, Ladapo said.
"I think as a nation we're all becoming more aware of the risks associated with opioids," he added. "And just general awareness is important, because I still think that this is a risk that's underrecognized."