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Benzodiazepines, With or Without Opioid Use, Associated With Increased Mortality

December 17, 2020

The use of benzodiazepines, with or without opioid cotreatment, significantly increases all-cause mortality risk compared with the use of low-risk antidepressants, according to a US-based study published online in JAMA Network Open.

“In particular, the benzodiazepine-opioid coprescription group continued to show a nearly 2-fold increase in all-cause mortality even after taking into account medical comorbidities and polypharmacy burden in adjusted analyses,” wrote researchers from Washington University School of Medicine in St. Louis, Missouri.

The retrospective cohort study included 5,212 adults age 20 and older from National Health and Nutrition Examination Surveys followed for a median 6.7 years. Researchers evaluated whether benzodiazepine use, with or without opioid use, was associated with increased mortality compared with low-risk selective serotonin reuptake inhibitors (SSRIs).

Majority of Opioid Overdose Deaths Among Youth Involve Multiple Substances

The study found a significant increase in all-cause mortality with benzodiazepine and opioid cotreatment (researchers reported a hazard ratio of 2.04) as well as with benzodiazepines without opioid cotreatment (which had a hazard ratio of 1.6) compared with SSRIs.

Subgroup analyses showed increased mortality risk with benzodiazepine use, with or without opioids, only among participants aged 65 years or younger—not older participants.

“We found no evidence of increased all-cause mortality stemming from benzodiazepine-opioid cotreatment in participants aged 65 years or older, which parallels similar null findings among elderly patients receiving benzodiazepines without opioids,” researchers wrote. “There was a consistently elevated mortality risk in participants younger than 65 years, which may be associated with surging drug poisoning–related mortality that disproportionately affects younger US populations.”

The authors called for a concerted effort by physicians, scientists, and policymakers to decrease overprescribing.

—Jolynn Tumolo


Xu KY, Hartz SM, Borodovsky JT, Bierut LJ, Grucza RA. Association between benzodiazepine use with or without opioid use and all-cause mortality in the United States, 1999-2015. JAMA Network Open. 2020;3(12):e2028557.

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