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The Dangers of Using Benzodiazepines and Opioids Together

Researchers from Stanford University analyzed health insurance claims from 2001 to 2013 to investigate a relationship between concurrent benzodiazepine and opioid use and opioid overdose. A significant increase in the incidence of current use and the risk of overdose was found in patients taking both types of medications.


Opioid abuse continues to be a growing problem in the United States with an estimated 2.1 million people abusing prescription opioids. Deaths from opioid overdoses have increased fourfold since 1999. Opioids are safe and effective in the treatment of pain when prescribed judiciously and used according to the instructions of prescribers; however, the misuse of opioids can lead to addiction and potentially fatal overdose. Prescriptions for opioids, which include medications related to morphine, such as oxycodone, hydromorphone, and codeine, have increased by almost 300% over the past 15 years.

Benzodiazepines (BZDs), which include drugs such as diazepam and lorazepam, can be used in a wide range of disease states including insomnia, muscle spasms, anxiety, and seizures. Recently, because the concurrent use of BZDs and opioids can have an additive effect on respiratory suppression, the FDA has issued a black box warning regarding the dangers of using these two classes of medications at the same time. About 30% of fatal opioid overdoses involve the use of a BZD.

In a recently published BMJ article, investigators from Stanford University completed a retrospective analysis of patients using private insurance claims to test an association between opioids and BZDs in overdoses that resulted in emergency room visits. Using data from Marketscan, a database consisting of 35 million patients with private insurance, researchers selected patients aged 18 to 64 who had continuous coverage from January 1, 2001, to December 31, 2013, and filled at least 1 opioid prescription (researchers did not consider opioid-based cough medications as inclusion criteria). Patients were excluded from the study if they had a diagnosis or history of cancer. Investigators identified overlaps in BZD and opioid usage and used statistical analyses to establish a relationship between those overlaps and opioid overdose.

The main outcomes that researchers measured were the percentage of opioid users with overlapping BZD usage, the incidence of emergency room visits for opioid overdoses, and the incidence of inpatient admission for opioid overdoses.

Investigators found that the incidence of using both BZDs and opioids at the same time increased by about 80% from 2001 to 2013. The incidence of hospitalizations and emergency room visits by patients using both drugs simultaneously was significantly greater. Researchers estimated that a 15% reduction in overdoses could be made by stopping the concurrent use of BZDs and opioids.

The inclusion criteria of continuous coverage may diminish the results of this study. There is a strong possibility that patients may have died from opioid overdose during the study’s time period; this would have reduced the overall incidence of overdoses. In addition, researchers were unable to account for illegal drug usage. The authors of this study hope that their results shed light on the dangers of using BZDs and opioids together and urge institutions to form educational programs to warn prescribers on dangerous prescriptive patterns.


Written By: Corey Cunningham, PharmD



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