Opioids and Benzodiazepines: The Deadly Breathing Risk When Taken Together

When opioids and benzodiazepines are taken together, the risk of stopping breathing doesn’t just go up-it explodes. This isn’t a theoretical concern. It’s a leading cause of accidental death in the U.S., and it’s happening to people who thought they were following their doctor’s orders.

Why This Combination Is So Dangerous

Opioids like oxycodone, hydrocodone, and fentanyl slow breathing by targeting mu-opioid receptors in the brainstem. Benzodiazepines like alprazolam, lorazepam, and diazepam do something similar but through a different pathway-they boost GABA, the brain’s main calming chemical. Alone, each drug can suppress breathing. Together, they don’t just add up-they multiply. The result? A deep, silent shutdown of the respiratory system that can happen without warning.

Studies show the overdose death rate for people taking both drugs is 10 times higher than for those taking opioids alone. In 2020, benzodiazepines were involved in 16% of all opioid-related overdose deaths, according to the CDC. That’s about 220 Americans dying every day from opioids, and nearly one in six of those deaths included a benzodiazepine.

What makes this even more terrifying is that people often don’t feel it coming. Someone might take their usual dose of oxycodone for back pain and a lorazepam for anxiety, and feel fine during the day. But at night, when they’re asleep, their breathing slows to dangerous levels. Oxygen drops. Carbon dioxide builds up. And because the brain’s alarm system is also suppressed, they don’t wake up.

How the Body Fails: The Science Behind the Collapse

The danger isn’t just about sedation. It’s about the body’s ability to respond to low oxygen and high carbon dioxide. Normally, when your blood oxygen drops, your brain tells you to breathe harder. But both opioids and benzodiazepines blunt that reflex.

One study found that 85% of people who took both drugs together had oxygen saturation fall below 90%-a level considered unsafe. Only 45% of those taking opioids alone hit that threshold. Even more alarming, some patients showed normal oxygen levels during brief clinical checks but collapsed hours later while sleeping.

There’s also a hidden chemical trap. Some opioids, like fentanyl and methadone, are broken down by the liver enzyme CYP3A4. Certain benzodiazepines, especially alprazolam, block that same enzyme. That means the opioid sticks around longer, building up in the bloodstream. A dose that was safe yesterday becomes lethal today.

Who’s at Highest Risk?

This isn’t just a problem for people who misuse drugs. It’s happening to older adults, chronic pain patients, and people with anxiety or PTSD who are prescribed both medications by different doctors.

The American Geriatrics Society lists this combination as potentially inappropriate for older adults because of the combined risks of falls, confusion, and breathing failure. In one study, nearly 15% of Medicare patients on long-term opioids were also getting benzodiazepines. That’s over a million people in the U.S. alone.

Even people who’ve been on opioids for years aren’t safe. Chronic opioid use builds tolerance to pain relief and euphoria-but not to respiratory depression. That means someone who’s been on high-dose oxycodone for years might still die from a low dose of diazepam.

What Doctors Are Told to Do

The FDA issued a formal warning in 2016 and strengthened it in 2019. Their message is clear: Don’t prescribe these together unless absolutely necessary. And even then, only under strict conditions.

The FDA says:

• Only use this combination if no other treatment works.
• Start with the lowest possible dose of the benzodiazepine.
• Monitor closely for drowsiness and slow breathing.
• Avoid opioid cough medicines entirely in patients taking benzodiazepines.

The CDC’s 2022 prescribing guidelines go even further: Avoid prescribing benzodiazepines with opioids whenever possible. Many hospitals now use electronic alerts to flag dangerous combinations before a prescription is filled. One study showed these alerts cut inappropriate co-prescribing by nearly 30%.

What Patients Need to Know

If you’re taking an opioid for pain and a benzodiazepine for sleep or anxiety, you need to talk to your doctor today. Don’t wait for a crisis.

Ask:

• Is this combination absolutely necessary?
• Are there safer alternatives for my anxiety or insomnia?
• What signs should I watch for that mean I’m in danger?
• Should my family or caregiver have naloxone on hand?

Naloxone can reverse an opioid overdose-but it doesn’t work on benzodiazepines. That means if you’re taking both, naloxone might not be enough. You need someone who knows how to recognize slow breathing and can call 911 immediately.

The Withdrawal Danger

Stopping either drug suddenly can be deadly. Opioid withdrawal causes intense flu-like symptoms, anxiety, and insomnia. Benzodiazepine withdrawal can trigger seizures, hallucinations, and even death.

That’s why quitting either drug cold turkey is never safe-especially if you’re on both. Tapering must be done slowly, under medical supervision. A doctor might reduce the benzodiazepine first, then the opioid, or vice versa, depending on your situation. There’s no one-size-fits-all plan.

What’s Being Done to Fix This?

The CDC awarded a $2.5 million research grant to UC Davis in 2022 to study this exact problem. Scientists are looking at who’s most vulnerable, why doctors keep prescribing this combo, and how to predict who’s at highest risk.

Some researchers are testing new pain medications that don’t affect breathing. Others are building AI tools that analyze a patient’s medical history to flag dangerous drug mixes before they’re prescribed.

In hospice care, where the goal is comfort not longevity, this combination may still be used. But even there, doctors are being more careful. They use lower doses, monitor constantly, and never give it to someone who isn’t already under palliative care.

Real Signs You’re in Danger

If you or someone you care for is taking both drugs, watch for these warning signs:

• Extreme drowsiness, even after a full night’s sleep
• Slurred speech or confusion
• Slow, shallow, or irregular breathing
• Blue lips or fingertips
• Difficulty waking up
• Unresponsiveness to loud noises or shaking

If you see any of these, call 911 immediately. Don’t wait. Don’t assume they’ll wake up on their own. This isn’t a case of being "too tired." This is respiratory failure.

What to Do If You’re Currently Taking Both

Don’t panic. Don’t quit cold turkey. Do this:

1. Make a list of every medication you’re taking, including over-the-counter drugs and supplements.
2. Schedule an appointment with your primary doctor or pain specialist.
3. Ask: "Is this combination still necessary? Are there safer options?"
4. If you’re told to taper, follow the plan exactly. Don’t skip doses or speed it up.
5. Teach a family member or friend how to recognize the signs of overdose and how to use naloxone.

Many people feel guilty or ashamed about taking these medications. But the problem isn’t you. It’s a system that allowed dangerous combinations to become common. You’re not failing-you’re taking the right step by asking questions.