Benzodiazepines and opioids: monitoring a deadly combination

Your patient, a 47-year-old female, has suffered from chronic pain since a car accident 18 months ago. Her pain became so severe that, 3 months ago, you prescribed hydrocodone. Now she sees you monthly to monitor the effectiveness of the drug.

During her most recent visit, she mentions that she has started seeing a psychiatrist to address her pain-related anxiety and depression and that she is considering taking medication that may help. What she doesn’t know is that certain medications, like benzodiazepines and opioids, don’t mix. In fact, they can have deadly consequences.

Growing awareness of a potentially fatal trend

According to the National Institute on Drug Abuse (NIDA), more than 30% of overdoses involving opioids also involve benzodiazepines,1 a trend with potentially fatal consequences. Both opioids and benzodiazepines depress the central nervous system. When combined, the dangers are magnified; the combination can cause respiratory suppression, cardiac distress, and even death.

In 2015, for example, 23% of people who died of an opioid overdose also tested positive for benzodiazepines.2 Research has shown that many patients are prescribed both drugs simultaneously, and that people concurrently using both drugs are at higher risk of visiting the emergency department or being admitted to a hospital for a drug-related emergency.3

In other words, the current opioid epidemic isn’t just about opioids. Just as opioid use has skyrocketed in recent years, benzodiazepine prescriptions have risen steadily, from 8.1 million in 1996 to 13.5 million in 2013, a 67% increase.4

What do the guidelines say?

The Centers for Disease Control and Prevention (CDC) now encourages clinical drug monitoring for patients on chronic opioid therapy,5 and the US Food and Drug Administration (FDA) issued a boxed warning on both prescription opioids and benzodiazepines, alerting prescribers to the dangers of concurrent use.

However, guidelines for monitoring overlapping prescriptions of opioids and benzodiazepines have not yet been established. That’s why clinicians who prescribe both drugs for patients must be extra cautious when doing so.

An additional challenge? Some patients may be obtaining and combining both medications without their clinician’s knowledge. Data from the 2018 Quest Diagnostics Health Trends™ report revealed that of the 20% of test results showing potentially dangerous concurrent use of opioids and benzodiazepines, 64% of these cases involved a drug that was not prescribed.6

Whether you’re prescribing both medications or your patients are combining non-prescription drugs on their own, implementing a clinical drug monitoring program can help.

Opioid monitoring and the CDC

Opioid prescription and management guidelines issued by the CDC in 2016 include the use of urine drug testing before starting opioid therapy, and consideration of urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit substances.

How drug monitoring can help

For clinicians, drug monitoring can provide insights into possible forms of misuse, including:

  • Substance use disorders
  • Dangerous drug combinations, including that of opioids and benzodiazepines
  • Treatment noncompliance
  • Diversion, or instances where the prescribed drug is not found in the patient’s specimen

Best practices include presumptive testing and confirming unexpected positives or negatives with definitive testing. This helps minimize over-testing while providing the right level of information needed to make informed decisions.

Clinical drug monitoring can detect misuse in patients, identifying those who are taking a medication not prescribed to them or in danger of deadly drug combinations. Such monitoring is guideline-supported. Making clinical drug monitoring standard practice for patients on long-term opioid therapy is a strategy that protects both patients and the practice, while giving you objective data about what drugs patients are taking so that you can take action to prevent or address potentially dangerous misuse.

Prevent the combination from turning deadly with help from Quest

Our Clinical Drug Monitoring program, with support from Quest toxicologists (1.877.40.RXTOX) and specialty representatives, can help protect you against misuse of pain pills. We offer the following:

  • A comprehensive portfolio of drug tests to identify the presence of prescribed, non-prescribed, and illicit drugs
  • Enhanced immunoassay sensitivity, with lower cutoff values to better detect the presence of benzodiazepines and opioids
  • medMATCH® reports, which highlight results that are inconsistent with the drugs you’ve prescribed
  • A medMATCH® trending report, so you can view a summary of your practice’s results, compare your medMATCH rates to Quest’s national database, and track positivity results

Learn more at



  1. National Institute on Drug Abuse (NIDA). Benzodiazepines and opioids. Revised March 2018. Accessed October 12, 2018.
  2. Centers for Disease Control and Prevention (CDC). Multiple cause of death, 1999–2015. CDC WONDER Online Database. Accessed October 15, 2018.
  3. Sun EC, Dixit A, Humphreys K, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760.
  4. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing benzodiazepine prescriptions and overdose mortality in the United States, 1996-2013. Am J Public Health. 2016;106(4):686-688. doi:10.2105/AJPH.2016.303061
  5. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65(No. RR-1):1-49.
  6. Quest Diagnostics. Health trends: drug misuse in America 2018. September 2018.
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