Benzodiazepines help patients cope with severe anxiety, panic disorder, or sleep problems; prescription opioids can help relieve severe pain. When prescribed appropriately and with sufficient monitoring, either medication is relatively safe, especially for short-term use.
If a health professional decides a patient needs the benefits of dual therapy—an opioid plus a benzodiazepine—careful monitoring becomes especially important. Either medication can cause respiratory depression, and the combined respiratory effects can lead to serious problems; overdose, even death. Yet, according to the authors of the study described below, dual prescribing is becoming an increasingly common therapeutic tool.
A team from Stanford University School of Medicine, the University of California at San Francisco, and the VA Palo Alto Health Care System, undertook a study to identify the effects of therapy combining an opioid with a benzodiazepine. Using data from 315,428 privately insured U.S. patients aged 18-64 who had dual prescriptions, the team determined the yearly incidence of hospital visits for opioid overdose. BMJ published the results of the study on March 14.
Dual Prescribing: Up Sharply
In 2001, only about 1 in 10 patients taking opioids were also taking a benzodiazepine; by 2013, the figure had almost doubled. Driving the increase was a rise in the number of patients taking an opioid intermittently rather than chronically.
Today, benzodiazepines are present in about 1 in 3 fatalities attributed to “opioid” overdoses, a finding that is causing increasing concern among policymakers and caregivers.
In 2016, two government agencies became sufficiently alarmed to take action. The Centers for Disease Control and Prevention (CDC) published guidelines urging clinicians to avoid prescribing benzodiazepines and opioids simultaneously. The Food and Drug Administration (FDA) established a requirement for Black Box warnings—the highest alert level—on product labels and other printed material, noting the problems associated with dual prescribing.
Key Data on Dual Prescribing
In their report, the authors of the BMJ study underscored key data:
- Patients who used opioids with benzodiazepines were at a “substantially higher risk” of emergency department visits or inpatient admissions for opioid overdose; moreover, the authors found that this group had a “tenfold increased risk of death from overdose”
- Providers could lower the risk of emergency room visits or inpatient admission for opioid overdose by 15%, by eliminating simultaneous use of benzodiazepines and opioids
The authors compared their results with those from several other studies:
- A VA study found that of patients using opioids, nearly one in three were also taking benzodiazepines; dual use was linked with an increased risk of death attributed to opioid overdose
- Almost 4 of every 5 patients taking an opioid were also taking a benzodiazepine; this group faced “a tenfold increased risk of death from overdose”
- A study in Ontario, Canada using toxicology analysis identified benzodiazepines as involved in 60% of deaths from opioid overdose
The authors do not make a blanket recommendation that dual prescribing should be eliminated, but they do recommend that providers “exercise caution in prescribing opioids for patients who are already using benzodiazepines (or vice versa), even in a non-chronic setting.”
Based on their data, they see a similar risk for chronic and intermittent opioid users, and they note that opioids “should be prescribed cautiously—even if only for a short term course—among patients who are also using benzodiazepines.”
The authors also suggest that policymakers and providers focus not just on opioid prescribing, but on benzodiazepine prescribing as well, so they “can play an important role in mitigating the risks of opioid prescriptions.”
They recommend educational programs warning prescribers and patients about the risks of dual prescribing, and suggest that the Veterans Health Administration’s system-wide opioid safety initiative (https://www.va.gov/PAINMANAGEMENT/Opioid_Safety_Initiative_Toolkit.asp) could be used as a model.
See related article in this issue on AATOD Issue Benzodiazepine Guidelines for OTPs available at: http://atforum.com/2017/04/aatod-issues-concise-focused-benzodiazepine-guidelines/
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;356:j760. doi: https://doi.org/10.1136/bmj.j760.
Karaca-Mandic P, Meara E, Morden NE. The growing problem of co-treatment with opioids and benzodiazepines [editorial]. BMJ. 2017;356:j1224. doi: https://doi.org/10.1136/bmj.j1224.