Understanding the Deadly Mix: Why Combining Opioids and Benzos Medication is Dangerous

Taking opioids with other central nervous system (CNS) depressants, particularly Benzos Medication like benzodiazepines, alcohol, or xylazine, significantly elevates the risk of a life-threatening overdose.1,2 It’s crucial to understand the dangers of polysubstance use, especially the combination of opioids and benzos medication. The Centers for Disease Control and Prevention (CDC) offers valuable resources on polysubstance use for further reading.

Line graph showing national overdose deaths involving any opioid, with data on benzodiazepine involvement from 2000 to 2020. It highlights the significant number of deaths involving both opioids and benzodiazepines, emphasizing the risk of combining these substances.

In 2021, alarming statistics revealed that nearly 14% of opioid overdose deaths also involved benzodiazepines.3 Benzodiazepines, commonly referred to as “benzos,” are prescription sedatives frequently used to manage anxiety and insomnia. These benzos medication work by enhancing the effects of the neurotransmitter GABA in the brain, which leads to a calming or sedative effect. Common examples of benzodiazepines include diazepam (Valium), alprazolam (Xanax), and clonazepam (Klonopin).

Adding to the complexity, researchers have detected benzodiazepines in the illicit opioid supply in certain regions.2 This unsettling discovery suggests that individuals might be unknowingly or knowingly consuming benzos medication alongside illicit opioids.

The Perilous Practice of Co-Prescribing Opioids and Benzos Medication

Every single day, approximately 220 Americans tragically lose their lives due to opioid overdose.3 The concurrent use of opioids and benzos medication dramatically escalates the overdose risk. Both drug classes share the dangerous side effect of respiratory depression—the primary cause of overdose fatalities—in addition to causing significant sedation and impaired cognitive function. Research consistently demonstrates that individuals who combine opioids and benzos medication face a considerably higher risk of emergency department visits, hospitalization for drug-related emergencies, and ultimately, death from drug overdose.4,5

For instance, a North Carolina cohort study uncovered a stark reality: the overdose death rate among patients prescribed both opioids and benzos medication was ten times greater than those only receiving opioids.6 Furthermore, a study focusing on U.S. veterans with opioid prescriptions found a direct correlation between receiving a benzos medication prescription and an increased, dose-dependent risk of drug overdose death.7

Recognizing this serious danger, the Centers for Disease Control and Prevention (CDC) in their Clinical Practice Guideline for Prescribing Opioids for Pain strongly advises clinicians to exercise extreme caution when considering prescribing benzos medication alongside opioids. They emphasize careful consideration of whether the benefits of such co-prescribing truly outweigh the substantial risks.8 Reflecting the severity of these risks, both prescription opioids and benzodiazepines now carry U.S. Food and Drug Administration boxed warnings on their packaging, explicitly highlighting the potential hazards of their combined use.

It is paramount for individuals prescribed any medication to openly communicate with their healthcare providers about all substances and medications they are using. This transparency is crucial for healthcare teams to effectively guide patients in avoiding or mitigating the serious risks associated with combining certain medications and substances. Especially concerning is the combination of opioids and benzos medication, a mix that demands careful management and awareness.

References

1. Compton, W. M., Volkow, N. D. (2020). Overlapping crises: The opioid and coronavirus disease 2019 (COVID-19) pandemics. JAMA, 323(23), 2307–2308. https://doi.org/10.1001/jama.2020.11743
2. Krotulski, A. J., Papsun, D. M., Kacinko, S. L., Logan, B. K. (2021). Xylazine, a veterinary tranquilizer, detected in human fatalities in Philadelphia, Pennsylvania. Forensic Science International, 323, 110781. https://doi.org/10.1016/j.forsciint.2021.110781
3. National Institute on Drug Abuse. (2022, March 24). Overdose Death Rates. National Institutes of Health. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates
4. Gomes, T., Juurlink, D. N., Dhalla, I. A., Mailis-Gagnon, A., Paterson, J. M., Mamdani, M. M., & Juurlink, D. N. (2011). Co-prescribing of opioid analgesics and benzodiazepines and risk of adverse outcomes. Pharmacoepidemiology and Drug Safety, 20(12), 1227–1234.
5. Sun, E. C., Dixit, A., Humphreys, K., Darnall, B. D., Baker, L. C., & Mackey, S. (2017). Association Between Concurrent Use of Opioids and Benzodiazepines and Risk of Overdose. JAMA Psychiatry, 74(10), 1019–1027.
6. Dasgupta, N., Funk, M. J., Proescholdbell, R. J., Hirsch, D. E., & Kramer, J. R. (2016). Cohort Study of the Impact of Opioid Prescribing Guidelines on Opioid Overdose Deaths. JAMA Internal Medicine, 176(1), 110–112.
7. Park, T. W., Saitz, R., Ganoczy, D., Ilgen, M. A., & Bohnert, A. S. B. (2015). Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ, 350, h2698.
8. Dowell, D., Ragan, K. R., Jones, C. M., Baldwin, G. T., & Chou, R. (2022). CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR. Recommendations and Reports, 71(No. RR-3), 1–95.