The Hidden Dangers of Benzodiazepine and Opiate Combinations

By: Mario Ramirez, MD

Reading Time: 3 minutes

Date: 08/10/2017

Filed Under: Clinician Perspective

With all of the recent attention cast on the national opioid epidemic and the increase in overdose deaths, one issue that seems to have fallen out of focus is the need for increased scrutiny on concomitant drug prescriptions, particularly benzodiazepines. The combination of opioids and benzodiazepines was found to be dangerous enough that dual prescribing of the two medications caused the FDA to issue black box warnings when prescribing each of these medications in 2016. An article originally published in Clinical Advisor (March 2017[1]) makes two important points:

  • Concurrent use of both benzodiazepines and opioids has increased by 80% between 2001 and 2013 and significantly increases the risk of overdose according to the British Medical Journal[2].
  • Use of these two medications together significantly increases the risk for an emergency department visit compared to the use of just one medication alone.

And a second editorial in the same BMJ issue by Karaca-Mandic, et al[3]., highlights the basic reason that AffirmHealth exists (paraphrased here): there is little coordination between patients and physicians around the use of these medications, and in today’s particularly busy clinical work places, there is high risk for a poor outcome because a good coordinating mechanism does not exist across different locations.

I’ve copied the article here for those interested in more detail:

Opioid/Benzodiazepine Combination Increases Risk of Overdose[1]

Concurrent benzodiazepine and opioid use increased by 80% between 2001 and 2013 in the United States and significantly contributes to the overall population risk of opioid overdose, according to data published in the BMJ.

Eric E. Sun, MD, PhD, from the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University School of Medicine, and colleagues sought to identify trends in the concurrent use of opioids and benzodiazepine and identify the impact of these trends on hospital admissions and emergency room visits for opioid overdose[2].

The researchers identified 315,428 privately insured participants between 18 and 64 years of age who filled at least 1 prescription for an opioid. They calculated the annual percentage of opioid users with concurrent benzodiazepine use and the annual incidence of visits to the emergency room and inpatient admissions for opioid overdose.

In 2001, 9% of opioid users also used a benzodiazepine, and the rate increased to 17% in 2013 (80% relative increase). The researchers noted that the increase was caused by increases among intermittent opioid users.

Concurrent use of opioids and benzodiazepine was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose compared with opioid users who did not use benzodiazepine (adjusted odds ratio, 2.14). The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose for intermittent users was 1.42, and the odds ratio for chronic opioid users was 1.81.

The investigators added that if this association is causal, elimination of concurrent use of these 2 medications could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by 15%.

“From a policy perspective, in addition to the current focus on opioid prescribing, policymakers and healthcare systems should also focus on benzodiazepine prescribing behaviors, as these behaviors can play an important role in mitigating the risks of opioid prescriptions,” the researchers concluded.

“Healthcare systems might also want to implement education programs that warn prescribers and patients about the risks of taking benzodiazepines and opioids concurrently, with the Veterans Health Administration's system-wide opioid safety initiative being a potential model to emulate.”

In an accompanying editorial, Pinar Karaca-Mandic, PhD, from the University of Minnesota, and Ellen Meara, PhD, and Nancy E Morden, MD, MPH, from Dartmouth College note that clinicians who care for patients who use opioids chronically should be particularly cautious, because opioids can be prescribed by multiple providers[3].

“Unless systems are set up to push information to providers, however, busy clinicians will struggle to keep up with their patients' use of different prescriptions,” they wrote. “A multi-pronged effort from both regulators and experts writing clinical guidelines, along with extensive expansion in warnings about the hazards of drug-drug interactions, are essential to reduce low value, potentially dangerous care.”

[1] Opioid/Benzodiazepine Combination Increases Risk of Overdose,, March 23rd, 2017.
[2] Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017. doi:10.1136/bmj.j760
[3] Karaca-Mandic, Meara E, Morden NE. The growing problem of co-treatment with opioids and benzodiazepines. BMJ. 2017. doi:10.1136/bmj.j1224

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