Benzodiazepines and Opioids: The Deadly Respiratory Risk
Jan, 2 2026
Drug Combination Risk Calculator
Based on CDC data: Patients taking both opioids and benzodiazepines are 10 times more likely to die from an overdose than those taking opioids alone.
This calculator uses clinical guidelines to estimate your risk level based on medication dosages. Always consult your doctor for personalized medical advice.
Example: 30mg oxycodone = 30 morphine equivalents
Example: 2mg alprazolam = 10 diazepam equivalents
When you take an opioid for pain and a benzodiazepine for anxiety, you might think you’re managing two separate problems. But what you’re really doing is putting your breathing at serious risk. The combination doesn’t just add danger-it multiplies it. This isn’t theoretical. It’s killing people right now.
Why This Combination Kills
Opioids slow your breathing by targeting specific brainstem areas that control how often you inhale and exhale. They stretch out the exhale, delay the next inhale, and eventually, if the dose is high enough, they stop breathing altogether. Benzodiazepines don’t work the same way, but they make it worse. They flood your nervous system with calming signals through GABA receptors, quieting everything-including the parts of your brain that keep you alive when you’re asleep or sedated. Together, they don’t just add up. They lock into each other’s pathways. Opioids hit the Kölliker-Fuse and preBötzinger Complex-key areas for rhythm control. Benzodiazepines amplify inhibition across those same zones. The result? A 78% drop in minute ventilation, according to a 2018 study. That’s not just sleepy. That’s life-threatening.The Numbers Don’t Lie
In 2019, benzodiazepines showed up in 17% of opioid overdose deaths involving prescription opioids-and in 22.5% of deaths tied to illicit opioids like heroin or fentanyl. By 2020, that number stayed stubbornly high: 17% of opioid-related fatalities still involved benzodiazepines. The CDC found that people taking both drugs are 10 times more likely to die from an overdose than those taking opioids alone. The worst part? These deaths aren’t random. They cluster in people aged 45 to 64, often those prescribed both drugs for chronic pain and anxiety. Many didn’t know the danger. Others were told the doses were “safe” because they were low. But safety isn’t about dose alone. It’s about the interaction. Even small amounts of both can be deadly when combined.What the Experts Say
The FDA slapped a black box warning on these drugs in 2016-the strongest warning they can give. It says: “Concomitant use can cause respiratory depression, sedation, coma, and death.” The American Society of Anesthesiologists says the same thing: avoid combining them whenever possible. Dr. Nora Volkow, head of the National Institute on Drug Abuse, put it bluntly: “The combination of opioids and benzodiazepines is particularly dangerous because both types of drugs can cause sedation and suppress breathing, and their combined effects can be lethal.” A 2020 review in the British Journal of Pharmacology called the effect “supra-additive”-meaning the danger isn’t just double. It’s exponential. One drug depresses breathing. The other shuts down the backup systems. The body doesn’t have a failsafe.
Why Naloxone Isn’t Enough
If someone overdoses on opioids, naloxone can reverse it. Fast. Effective. Life-saving. But if benzodiazepines are in the system, naloxone won’t touch them. It doesn’t block GABA receptors. It doesn’t fix the breathing suppression caused by Xanax, Valium, or Klonopin. That means even if you give naloxone and the person wakes up, they might still stop breathing again-because the benzodiazepine is still active. Emergency responders now carry naloxone, but they’re also trained to watch for signs of benzodiazepine involvement. And they’re seeing more cases where multiple doses of naloxone are needed, not because of high opioid doses, but because the benzodiazepine keeps pulling the person back under.What Doctors Are Doing Differently
After the 2016 FDA warning, concurrent prescribing dropped by 14.5% nationally. That’s progress. But 8.7% of long-term opioid patients are still getting benzodiazepines. Why? Because anxiety is real. Pain is real. And sometimes, doctors feel trapped. The CDC’s 2016 guidelines say: avoid combining them. If you absolutely must, use the lowest possible dose for the shortest time. But alternatives exist. For anxiety, SSRIs like sertraline or buspirone work without suppressing breathing. For muscle spasms or insomnia, non-benzodiazepine options like gabapentin or melatonin can be safer. For pain, non-opioid treatments-physical therapy, NSAIDs, nerve blocks, cognitive behavioral therapy-can reduce or eliminate the need for opioids altogether. Many clinics now screen for anxiety before prescribing opioids. If someone’s on both, they’re flagged for review.