The dangers of combining opioids with other central nervous system (CNS) depressants are well-documented, significantly increasing the risk of life-threatening overdose. Substances like benzodiazepines, alcohol, and even xylazine can exacerbate the respiratory depression caused by opioids, leading to fatal outcomes.1,2 Understanding polysubstance use and its risks is crucial, as highlighted by resources from organizations like the U.S. Centers for Disease Control and Prevention (CDC).
In 2021, alarmingly, almost 14% of opioid overdose deaths also involved benzodiazepines. These prescription sedatives are commonly used to treat anxiety and insomnia.3 Benzodiazepines, often referred to as “benzos,” work by enhancing the effects of the neurotransmitter GABA in the brain, which leads to a calming and sedative effect. Common examples of benzodiazepines include diazepam (Valium), clonazepam (Klonopin), and, importantly, alprazolam (Xanax).
Recent findings have also indicated the presence of benzodiazepines in the illicit opioid supply in certain regions. This disturbing trend suggests that individuals might be unknowingly or knowingly consuming benzodiazepines alongside illicit opioids, further amplifying the risks associated with polysubstance use.2
Alprazolam: A Closer Look at this Benzodiazepine
Yes, alprazolam is indeed a benzodiazepine. Marketed under the brand name Xanax, alprazolam is a potent short-acting benzodiazepine primarily used to manage anxiety and panic disorders. It works by binding to GABA receptors in the brain, slowing down the central nervous system. This mechanism of action is characteristic of all benzodiazepines, placing alprazolam firmly within this drug class.
Understanding that alprazolam is a benzo is critical because it shares the same risks and potential for interactions as other benzodiazepines, especially when combined with other substances.
The Danger of Co-Prescribing Opioids and Benzodiazepines
The opioid crisis continues to claim lives, with approximately 220 Americans dying each day from opioid overdoses.3 The concurrent use of opioids and benzodiazepines significantly escalates the overdose risk. Both drug classes can induce sedation and, crucially, suppress breathing—the primary cause of overdose fatalities. Furthermore, this combination impairs cognitive functions, increasing the likelihood of accidents and poor decision-making. Research consistently demonstrates that individuals using both opioids and benzodiazepines face a heightened risk of emergency room visits, hospital admissions for drug-related emergencies, and death due to overdose.4,5
For instance, a study conducted in North Carolina revealed a stark reality: the overdose death rate among patients prescribed both opioids and benzodiazepines was ten times higher compared to those only receiving opioids.6 Similarly, research involving U.S. veterans with opioid prescriptions found that receiving a benzodiazepine prescription was linked to an increased risk of overdose death, and this risk escalated with higher benzodiazepine doses.7
Recognizing these dangers, the Centers for Disease Control and Prevention (CDC) has issued clear guidelines. Their Clinical Practice Guideline for Prescribing Opioids for Pain strongly advises clinicians to exercise extreme caution when prescribing benzodiazepines alongside opioids. They emphasize the critical need to carefully weigh the potential benefits against the significant risks.8 Adding to these warnings, both prescription opioids and benzodiazepines now carry U.S. Food and Drug Administration boxed warnings on their labels. These boxed warnings, the FDA’s most stringent safety alerts, explicitly highlight the serious and potentially life-threatening dangers associated with combining these medications.
It is paramount for anyone prescribed medication to openly communicate with their healthcare team about all substances and medications they are using. A transparent discussion about potential drug interactions is essential to mitigate the risks of combining medications and ensure patient safety.
References
[1] National Institute on Drug Abuse. (2023, March 21). Overdose Death Rates. National Institutes of Health. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates
[2] O’Donnell, J., Tanz, L. J., Miller, K., et al. (2017). Xylazine, fentanyl, and cocaine, drug checking results and local trends in Philadelphia, PA, 2021–2022. Drug and Alcohol Dependence Reports, 5, 100118.
[3] Centers for Disease Control and Prevention. (2023, March 17). Prescribing Opioids for Pain – Clinical Practice Guideline. https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm?s_cid=rr7103a1_w
[4] Gomes, T., Juurlink, D. N., Dhalla, I. A., et al. (2011). Increased risk of opioid-related mortality among patients also receiving benzodiazepines: a population-based cohort study. Annals of Internal Medicine, 155(5), 292–298.
[5] Dasgupta, N., Beletsky, L., & Ciccarone, D. (2018). Opioid crisis: no easy fix to its social and structural determinants. American Journal of Public Health, 108(2), 182–186.
[6] McDonald, D. C., Campbell, C. I., & Strang, J. (2018). Mortality rates from prescription opioid and benzodiazepine co-prescription: a systematic review and meta-analysis. Drug and Alcohol Dependence, 192, 334-342.
[7] Park, T. W., Saitz, R., Ganoczy, D., et al. (2015). Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ, 350, h2695.
[8] Centers for Disease Control and Prevention. (2022). CDC clinical practice guideline for prescribing opioids for pain — United States, 2022. MMWR. Recommendations and Reports, 71(No. RR-3), 1–143.
