A team of UC Davis Health researchers led by Joshua Fenton received a 3-year $1.05 million grant from the Centers for Disease Control and Prevention (CDC) to identify risk and protective factors linked to the combined use of opioids and benzodiazepines, a group of drugs used to treat anxiety and insomnia.
Millions of patients prescribed opioids for chronic pain are co-prescribed benzodiazepines, commonly referred to as “benzos.” However, the combined use may increase overdose risk for patients on long-term opioid therapy.
Benzodiazepines are depressants with a sedative effect that reduces the activity of nerves in the brain. Two common benzos are the prescription drugs Valium® and Xanax®.
“Benzodiazepines are prescribed to about 25% of patients on long-term opioids. They magnify the risks of overdose considerably,” said Fenton, professor and vice chair of research in the Department of Family and Community Medicine at UC Davis School of Medicine and principal investigator of the study.
Risks of depressant dependency for patients taking opioids
Combining opioids with benzos can increase the overdose risk. Both drugs can cause sedation and suppress breathing—the main cause of overdose fatality —and impair cognitive function.
According to the National Institute on Drug Abuse, nearly 200 Americans die after overdosing on opioids every day. In 2020, 16% of overdose deaths due to opioids involved benzodiazepines. The overdose death rate among patients taking both types of medications was 10 times higher than among those only taking opioids.
“Benzodiazepines create significant physical dependency and decreasing doses can pose risks of withdrawal and seizures. So, once established, patients are often stuck on this hazardous drug combination,” Fenton said.
Benzodiazepines create significant physical dependency and decreasing doses can pose risks of withdrawal and seizures. So, once established, patients are often stuck on this hazardous drug combination.”
Assessing the overdose risks of polydrug use
The grant will fund a set of studies to identify factors, prescribing patterns, and dose trajectories of opioid and benzodiazepine use. They will look at:
- the initiation of long-term opioid-benzo co-prescriptions
- the prescription drug overdose (both fatal and nonfatal) after opioid-benzo co-prescription
- the polydrug overdose (involving opioids and other drugs, including fentanyl or psychostimulants) in patients co-prescribed opioids and benzos
The researchers will analyze patient groups in two large data sources: California CURES data linked to death records and the OptumLabs data, a national database of claims from commercial and Medicare Advantage enrollees. Findings from the study might help inform health care initiatives to mitigate overdose risk, especially for those caused by opioid and benzodiazepine co-prescribing.
“We expect that study results will help identify possible safer approaches to lowering doses for one or both drugs after the combination treatment is established,” said Stephen Henry, associate professor of internal medicine, faculty member at the Center of Healthcare Policy and Research (CHPR) and co-principal investigator on the study.
This work is in collaboration with CHPR researchers, including Iraklis Tseregounis, Susan Stewart and Alicia Agnoli.