Opioids and Benzodiazepines: How Their Combination Can Stop Your Breathing

When you take opioids and benzodiazepines together, your breathing can slow down-so much that it stops. This isn’t a rare accident. It’s a predictable, well-documented danger that kills hundreds of Americans every week. The FDA first sounded the alarm in 2016, then strengthened its warning in 2019. By then, data showed that people taking both drugs were 10 times more likely to die from an overdose than those taking opioids alone. And yet, even today, this deadly mix is still prescribed far too often.

Why This Combination Is So Dangerous

Opioids like oxycodone, hydrocodone, and fentanyl work by binding to receptors in your brainstem that control breathing. Benzodiazepines like alprazolam, lorazepam, and diazepam boost the effect of GABA, a calming neurotransmitter that also slows down brain activity, including the signals that tell you to breathe. Alone, each drug can suppress breathing. Together, they don’t just add up-they multiply.

A 2021 review in the Annals of Palliative Medicine found that when people took both drugs, their blood oxygen levels dropped below 90% in 85% of cases. With opioids alone, that number was only 45%. That’s not a small difference. It’s the gap between feeling drowsy and slipping into respiratory arrest.

The danger doesn’t stop at brain chemistry. Some opioids, like fentanyl and methadone, are broken down by the same liver enzyme (CYP3A4) that processes certain benzodiazepines. When you take them together, the benzodiazepine can block that enzyme, causing opioids to build up in your blood. You might be taking what your doctor calls a "normal" dose-but your body is getting a much stronger, longer-lasting hit than intended.

Who’s Most at Risk

Older adults are especially vulnerable. The American Geriatrics Society lists this combination as a "potentially inappropriate" medication for people over 65. Why? Because aging slows how the body processes drugs, reduces lung capacity, and increases the chance of falls-especially when you’re sedated. A 70-year-old on oxycodone for back pain and lorazepam for anxiety isn’t just at risk for an overdose. They’re at risk for choking on their own saliva, falling, breaking a hip, and never recovering.

People with sleep apnea are also in extreme danger. Both opioids and benzodiazepines relax the muscles in your throat, making airway blockages worse. One study showed that patients with sleep apnea who took both drugs had up to 15 times more breathing pauses per hour than those taking either drug alone.

Even people who’ve been on opioids for years aren’t safe. Many assume they’ve built up a tolerance-that their bodies can handle more. But tolerance to the pain-relieving effects doesn’t protect you from the breathing suppression caused by benzodiazepines. A person who’s been on high-dose opioids for years can still die from a single dose of alprazolam if they’re not careful.

What Happens During an Overdose

An overdose from this combination doesn’t always look like a movie scene. There’s no dramatic collapse. Often, it starts quietly: extreme drowsiness, slurred speech, confusion, slow breathing. The person might seem like they’re just "really tired." But their body is shutting down from the inside.

Oxygen levels drop. Carbon dioxide builds up. The brain stops sending signals to breathe. Within minutes, the person slips into unconsciousness. If they’re alone-sleeping, watching TV, lying down-they may not be found in time. Emergency responders often arrive to find someone with shallow, irregular breaths, blue lips, and no response to pain.

In 2020, 16% of all opioid-related overdose deaths in the U.S. involved benzodiazepines. That’s about 220 people every day. Many of them were prescribed both drugs by the same doctor. Some were taking them as directed. Others were using them as they were told to.

What Doctors Are Supposed to Do

The FDA says this combination should only be used when no other options exist. Even then, they recommend starting with the lowest possible dose of both drugs and monitoring closely. If a patient is already on an opioid and needs a benzodiazepine, the doctor should lower the opioid dose first. If a patient is on a benzodiazepine and needs an opioid, the opioid should be started at half the usual dose.

The CDC’s 2022 guidelines say clearly: "Avoid prescribing benzodiazepines concurrently with opioids whenever possible." Many hospitals now use electronic alerts in their systems to flag when a doctor tries to write a prescription for both. One study showed these alerts cut dangerous co-prescribing by nearly 30%.

But warnings don’t always reach the right people. A 2021 study of Medicare patients found that 15% of those on long-term opioids were also getting benzodiazepines. That’s millions of people. And 4.3% of them were on high-risk combinations-extended-release opioids with long-acting benzos-exactly the kind that stay in the system the longest and carry the highest danger.

What You Should Do If You’re Taking Both

If you’re on opioids and benzodiazepines together, don’t panic. But do act.

First, talk to your doctor. Ask: "Is this combination absolutely necessary? Are there safer alternatives?" There are non-addictive pain relievers like gabapentin or physical therapy for chronic pain. For anxiety, cognitive behavioral therapy (CBT) or SSRIs often work better than benzodiazepines in the long run.

If you can’t stop one of the drugs right away, don’t quit cold turkey. Stopping benzodiazepines suddenly can cause seizures. Stopping opioids suddenly can trigger severe withdrawal-sweating, vomiting, rapid heartbeat, insomnia. Both require a slow, supervised taper.

Keep naloxone on hand. Naloxone (Narcan) can reverse an opioid overdose, but it doesn’t work on benzodiazepines. Still, if opioids are part of the mix, naloxone could save your life. Make sure someone you live with knows how to use it.

Never drink alcohol or take other sedatives-sleep aids, muscle relaxers, even some over-the-counter cold medicines-while on this combination. Each one adds another layer of risk.

What to Watch For

Know the warning signs:

• Unusual drowsiness-even after a full night’s sleep
• Difficulty staying awake during conversations
• Shallow or slow breathing (fewer than 10 breaths per minute)
• Blue lips or fingertips
• Confusion, slurred speech, or inability to wake up

If you or someone you know shows these signs, call 911 immediately. Don’t wait. Don’t try to "sleep it off." Breathing can stop without warning.

The Bigger Picture

This isn’t just about bad prescriptions. It’s about a system that often treats pain and anxiety as separate problems-when they’re often connected. A person with chronic pain might develop anxiety. A person with anxiety might turn to opioids for sleep. The medical system sometimes responds by prescribing both drugs, without fully understanding the risk.

Research is now focused on finding safer alternatives. New pain medications are being developed that don’t affect breathing. Better screening tools are being tested to identify who’s most vulnerable. And more doctors are learning to treat the root causes-instead of just the symptoms.

But until then, the message is clear: combining opioids and benzodiazepines is one of the most dangerous things you can do to your body. It doesn’t just increase risk. It multiplies it. And the cost is measured in lives.

What Comes Next

If you’re on both drugs, the next step isn’t to panic-it’s to plan. Schedule a conversation with your doctor. Bring a list of everything you take, including supplements and over-the-counter meds. Ask about non-drug treatments. Ask about tapering. Ask about naloxone. You have the right to understand your risks-and to make safer choices.

This isn’t just about avoiding an overdose. It’s about reclaiming your health. You don’t have to live with constant sedation. There are better ways to manage pain and anxiety. They take more time, sometimes more effort-but they don’t put your life on the line every day.