Diphenhydramine Overdose: Signs, Risks, and Emergency Treatment

Most people think of diphenhydramine as a harmless sleep aid or allergy pill. You grab a Benadryl when you can’t sleep, or when your skin itches, or when you’re stuck in a car on a long road trip. It’s cheap. It’s over-the-counter. It’s everywhere. But take too much-just a few extra pills-and what starts as a sleepy pill can turn into a medical emergency that lands you in the ER with seizures, a racing heart, or even cardiac arrest.

What Happens When You Take Too Much Diphenhydramine?

Diphenhydramine is a first-generation antihistamine. At normal doses-25 to 50 mg every 4 to 6 hours-it blocks histamine to calm allergies and dries up runny noses. But it also blocks another key chemical in your brain: acetylcholine. That’s why it makes you drowsy. At high doses, this anticholinergic effect goes off the rails.

When someone takes more than 5 mg per kilogram of body weight (about 350 mg for a 150-pound person), symptoms start showing up. Above 20 mg/kg (around 1,400 mg), things turn dangerous. This isn’t rare. In 2022, U.S. poison centers logged over 12,000 cases of diphenhydramine overdose. About 30% of those were intentional, mostly among teens and young adults drawn in by dangerous social media challenges.

The classic signs are easy to remember with the rhyme: Dry as a bone, red as a beet, blind as a bat, mad as a hatter, hot as hades, full as a flask.

• Dry as a bone: No saliva, no sweat. Your mouth feels like cotton. Your skin is dry and warm.
• Red as a beet: Your face and chest flush red. It looks like a bad sunburn.
• Blind as a bat: Your pupils are huge, fixed, and unresponsive to light. You can’t focus. Everything is blurry.
• Mad as a hatter: Confusion, hallucinations, paranoia. People see things that aren’t there. They think they’re being chased or that their skin is crawling.
• Hot as hades: Body temperature spikes. Over 104°F (40°C) is common. This isn’t just feeling warm-it’s a medical emergency.
• Full as a flask: You can’t pee. Your bladder swells. Catheters are often needed.

Why the Heart Is at Risk

Here’s what most people don’t know: diphenhydramine doesn’t just mess with your brain. It acts like a tricyclic antidepressant in overdose-blocking sodium channels in your heart muscle. That’s why an EKG is critical.

On an EKG, you’ll look for two red flags:

• QRS widening: Normal is under 100 milliseconds. Over 100 ms means your heart’s electrical signal is slowing down. This raises the risk of dangerous arrhythmias.
• QTc prolongation: Normal is under 450 ms for men, 470 ms for women. When it stretches past 500 ms, your heart can flip into torsades de pointes-a life-threatening rhythm that can lead to sudden death.

These changes don’t always show up right away. They can sneak in 2 to 4 hours after ingestion. That’s why even if you feel okay after taking a big dose, you still need to be monitored for hours.

Cardiac arrest from diphenhydramine is rare-but it happens. And when it does, standard CPR often isn’t enough. Doctors may need to use sodium bicarbonate to reverse the sodium channel block, or even ECMO-a machine that takes over heart and lung function.

What Happens in the Emergency Room?

If you or someone else overdoses, call poison control immediately: 1-800-222-1222. Don’t wait for symptoms. Don’t try to induce vomiting. Get help fast.

In the ER, the first thing they do is check your ABCs: airway, breathing, circulation. Then they run tests:

• Continuous heart monitor (to catch arrhythmias)
• ECG (to check QRS and QTc)
• Basic metabolic panel (to see kidney and electrolyte status)
• Creatine phosphokinase (CPK) to check for muscle breakdown
• Acetaminophen level (because Tylenol PM contains both diphenhydramine and acetaminophen)

Here’s the key: blood levels of diphenhydramine don’t help doctors decide what to do. You can have a high level and be fine, or a low level and be crashing. Symptoms guide treatment-not numbers on a lab report.

How Doctors Treat It

Treatment is all about managing symptoms. There’s no antidote, but there are tools.

For agitation and seizures: Benzodiazepines like lorazepam or diazepam are first-line. They calm the brain and stop seizures. These are safe and effective.

For hallucinations and severe delirium: Physostigmine is the most powerful tool. It reverses the anticholinergic effects by boosting acetylcholine in the brain. Studies show it works better than sedatives-87% of patients improve with physostigmine, compared to only 24% with benzodiazepines alone. It’s not used if the patient has heart block or seizures, but when safe, it can clear confusion in minutes.

For QRS widening: Sodium bicarbonate. A bolus of 1-2 mEq/kg, then a drip. This helps the heart conduct electricity properly again.

For QTc prolongation: Magnesium sulfate. A 2-gram IV push can stabilize the heart rhythm.

For high fever: Cooling blankets, ice packs, fans. Fever above 102.2°F (39°C) can damage organs. You can’t just give Tylenol-it won’t work. The brain’s thermostat is broken.

For urinary retention: A catheter. This isn’t optional. A bloated bladder can rupture. About 35-40% of moderate to severe cases need one.

And yes-some ERs now use intravenous lipid emulsion (like Intralipid) for severe cardiovascular collapse. It’s not standard yet, but it’s been used successfully in cases where everything else failed.

Who’s at Risk-and Why It’s Getting Worse

Children under 6 often overdose accidentally. They find the bottle, think it’s candy. But the biggest surge is in teens and young adults.

Since 2018, intentional overdoses in the 13-19 age group have tripled. Why? TikTok, Reddit, YouTube. There are videos showing people taking 10, 20, even 30 pills to get “high.” One Reddit user wrote: “Took 600 mg thinking I could get high. Woke up in the ER with a catheter.”

They don’t realize they’re not getting a buzz-they’re poisoning their brain and heart. The hallucinations aren’t fun. They’re terrifying. The paralysis isn’t a trip-it’s a medical crisis.

The American Academy of Pediatrics launched the “Don’t Take the Benadryl Challenge” campaign. The FDA issued warnings. But the videos keep coming.

Recovery and Long-Term Effects

If you survive the acute phase, recovery can still be rough. Most people feel groggy for 24 to 48 hours. Confusion lingers. Some report memory gaps. Urinary retention can take days to resolve. In rare cases, rhabdomyolysis (muscle breakdown) leads to kidney damage requiring dialysis.

One ER doctor in Chicago treated 12 overdose cases this year. All recovered. But she says: “Every single one said they thought it was safe because it’s OTC. That’s the tragedy.”

Observation time matters. Even if you seem fine after 4 hours, if your heart was abnormal or you had hallucinations, you need at least 6 hours of monitoring. Discharge too early, and you could crash later.

What You Should Know

Diphenhydramine isn’t harmless. It’s a powerful drug with a narrow safety margin. What’s safe in one pill becomes deadly in five.

Here’s what to do:

• Never take more than the label says.
• Don’t combine it with alcohol, sleeping pills, or other sedatives.
• Keep it locked up if you have kids or teens at home.
• If you suspect an overdose-call poison control now. Don’t wait for symptoms.
• Know the signs: dry mouth, flushed skin, dilated pupils, confusion, fast heart rate, high fever.
• Don’t assume it’s “just a sleep aid.” It can kill.

Over-the-counter doesn’t mean risk-free. In the right dose, diphenhydramine helps. In the wrong dose, it destroys. And the line between the two is thinner than most people think.