What are the risks of co-prescribing opioids and benzodiazepines?


Opioids are a class of medications that are used for pain that is moderate to severe. They are often prescribed after serious injury or for pain related to cancer.1 When used for a short period of time they are generally safe. However, abuse of these medications can lead to addiction, overdose, and death. In the United States alone there were an estimated 42,000 opioid-related overdose deaths in 2016.2

Opioids work by activating opioid receptors on nerve cells which block pain messages being sent to the brain. This leads to a euphoric effect in the body, which may be the reason some people misuse these medications. 2 Opioids have many other adverse effects. These may include increased sensitivity to pain; depression; confusion or sleepiness; dizziness; constipation; nausea, vomiting, or dry mouth; itching and sweating; and low levels of testosterone. 1 In some cases slowed heart rate, shallow breathing, and loss of consciousness may occur.3

Benzodiazepines are a class of medications that have a sedating or calming effect on the body. They are mostly used to help with sleep problems or anxiety.4 They can also be used for pain disorder, alcohol withdrawal, muscle convulsions and seizures.5 Benzodiazepine use has increased dramatically over the last decade. From 1996 to 2013 the number of people being prescribed a benzodiazepine rose by 67%.4 There is a risk of dependence and tolerance to these medications.

Benzodiazepines work by increasing the effect of a chemical called GABA (gamma amino butyric acid) in the brain.5 This decreases brain activity and allows for central nervous system depression. Side effects of these medications include drowsiness, increased reaction time, slurred speech, short-term memory loss, depression, hallucinations, and paranoia. High doses of benzodiazepines aren’t usually fatal but can be when mixed with alcohol or opioids.


It is estimated that 115 Americans die every day due to overdosing on opioids and more than 30% of these overdoses involve benzodiazepines.4 Prescribing these two classes of medications together can be very dangerous. A cohort study published in 2016 found the risk of overdose death was 10 times higher in patients who were co-prescribed benzodiazepines and opioids compared to opioids alone.6

The reason that co-prescribing benzodiazepines and opioids can be dangerous is that both of these medications have serious sedating side effects. They can also suppress or stop breathing – which can lead to death. Opioids and benzodiazepines can impair cognitive thinking skills.

In 2016 the Centers for Disease Control and Prevention recommended that clinicians avoid prescribing benzodiazepines and opioids together when possible.4 An FDA black box warning is now on both classes of medications, which highlights the risks associated when they are taken together.


  1. Prescription Opioids. Centers for Disease Control and Prevention. https://www.cdc.gov/drugoverdose/opioids/prescribed.html. Revised August 29, 2017. Accessed November 26, 2019.
  2. How Opioid Drugs Activate Receptors. National Institutes of Health. https://www.nih.gov/news-events/nih-research-matters/how-opioid-drugs-activate-receptors. Published May 22, 2018. Accessed December 9, 2019.
  3. What are Opioids? American Society of Anesthesiologists. https://www.asahq.org/whensecondscount/pain-management/opioid-treatment/what-are-opioids/. Accessed November 26, 2019.
  4. Benzodiazepines and Opioids. National Institute on Drug Abuse. https://www.drugabuse.gov/drugs-abuse/opioids/benzodiazepines-opioids. Revised March 2018. Accessed November 26, 2019.
  5. Benzodiazepines. Drug Enforcement Administration. https://www.deadiversion.usdoj.gov/drug_chem_info/benzo.pdf. Published July 2019. Accessed December 9, 2019.
  6. Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med. 2016;17(1):85-98.

Prepared by:
Amy Madhiwala, PharmD
Clinical Instructor
University of Illinois at Chicago College of Pharmacy

The information presented is current as of November 2019. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.