There’s a pill in almost every American medicine cabinet. It promises to ease your aches, help you drift off to sleep, and make those restless nights feel a little less cruel. Its name? Tylenol PM. But one doctor is urging people to think twice before popping those tiny blue tablets into their mouths night after night.
Dr. Ethan Melillo, a pharmacist from Rhode Island, doesn’t mince words. He says Tylenol PM is one of the medications he “hates”—a strong sentiment in the world of medicine. But his frustration doesn’t stem from the drug’s effectiveness. Instead, it’s about how it’s being used—and more importantly, how it misleads users into thinking it’s completely safe.
Tylenol PM: A One-Two Punch of Trouble
Tylenol PM isn’t just one drug. It’s a combo—a tag team of two powerful ingredients:
- Acetaminophen, a pain reliever and fever reducer.
- Diphenhydramine, an antihistamine often used to make people drowsy.
At first glance, this combination seems like a clever way to fight off pain and insomnia in one go. But Dr. Melillo warns that the convenience may come at a serious long-term cost.
Let’s Talk About Acetaminophen: The Liver’s Hidden Foe
Acetaminophen (the active ingredient in regular Tylenol) is one of the most commonly used painkillers in the U.S. It’s affordable, easy to get, and gentler on the stomach than alternatives like ibuprofen. But it carries a big catch—especially for your liver.
Here’s what happens behind the scenes when you take acetaminophen: your liver breaks it down, and in the process, it creates a tiny amount of a toxic substance called NAPQI (N-acetyl-p-benzoquinone imine, if you’re feeling brave). Normally, your body handles this easily, using a natural antioxidant called glutathione to clean up the mess.
But if you:
- Take too much acetaminophen in one day,
- Use it regularly over time, or
- Have low levels of glutathione (which can happen if you drink alcohol frequently, are malnourished, or have certain health conditions),
…then your liver may not be able to keep up. That toxic byproduct, NAPQI, starts to build up. It binds to your liver’s cells, damaging them and, in severe cases, triggering liver failure.
Dr. Melillo points out that 4,000 milligrams of acetaminophen per day is the max safe dose for most adults. That’s roughly eight Tylenol PM tablets in 24 hours. It’s surprisingly easy to cross that line—especially since acetaminophen hides in many other over-the-counter meds for cold, flu, or sinus congestion.
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Why So Many Americans Are at Risk
It’s estimated that one in three Americans has some form of liver disease—that’s over 100 million people. Many may not even realize they’re damaging their liver with common medications.
In fact, concerns became so widespread that in 2011, the U.S. Food and Drug Administration (FDA) stepped in. They asked drug manufacturers to limit the amount of acetaminophen in combination products (like Tylenol PM) to no more than 325 mg per tablet.
Why? Because studies showed higher doses didn’t offer much extra pain relief—but they did make liver injury more likely.
And yet, Tylenol PM still contains 500 mg of acetaminophen per pill.
Diphenhydramine: A Sleep Aid With a Cognitive Price Tag
Now, let’s shift to Tylenol PM’s second ingredient: diphenhydramine. You might know it better as Benadryl, a classic allergy med. It’s what gives Tylenol PM its sleep-inducing power. But its drowsy effects come at a cost, especially when used habitually.
Diphenhydramine is an anticholinergic, meaning it blocks the action of a brain chemical called acetylcholine. Acetylcholine is essential for memory, learning, and cognitive function.
Block it too much or for too long, and problems start to surface. One study showed that people who took anticholinergic meds daily for three years or longer had a 54% higher risk of dementia compared to those who used them occasionally.
Other effects of diphenhydramine include:
- Dry mouth
- Dizziness
- Confusion (especially in older adults)
- Urinary retention—a condition that can cause further complications in elderly patients
Dr. Melillo emphasizes that these side effects might sound minor, but they can trigger or worsen age-related health problems, such as falls, dehydration, or delirium.
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Tylenol PM and Risk-Taking Behavior?
Here’s a curveball you might not expect: acetaminophen could also affect your emotions and decision-making.
A 2020 study by Ohio State University asked participants to take either 1,000 mg of acetaminophen or a placebo, then rate how risky certain activities seemed—think skydiving, bungee jumping, or making big career changes.
Surprisingly, those who took acetaminophen saw these activities as less dangerous than those who didn’t. Researchers believe the drug dulls emotional responses, reducing both fear and excitement. Earlier studies even found that acetaminophen can blunt empathy, lowering concern for others’ pain and even reducing joy.
So not only can this common drug affect your liver and memory—it might even change how you perceive the world.
What’s the Alternative?
Dr. Melillo isn’t out to ban Tylenol PM altogether. He acknowledges that it can be helpful in occasional situations. But he’s crystal clear on one thing: it shouldn’t be your nightly go-to.
If you’re having trouble sleeping, he suggests talking to a doctor or pharmacist about:
- Non-habit-forming sleep aids
- Melatonin or other natural supplements
- Sleep hygiene techniques like reducing screen time, avoiding caffeine after noon, and setting a consistent bedtime
- Cognitive behavioral therapy for insomnia (CBT-I), which has been shown to be more effective than meds in the long term
And if pain is keeping you up at night? Try:
- Using acetaminophen sparingly, and only when needed
- Rotating medications instead of using the same one daily
- Exploring non-drug pain management techniques like heat packs, massage, or stretching
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The Bottom Line: Proceed with Caution
Tylenol PM might seem like a simple fix for pain and sleepless nights, but behind the soothing label lies a more complicated story.
The risks—liver damage, memory issues, emotional blunting, and even potential dementia—are real, especially with regular use. That’s why Dr. Melillo urges people to use it only occasionally, and to stay informed about what’s really in the pills they’re taking.
As he puts it:
“If you’re someone who takes this once in a blue moon, then that’s fine—it’s not a big deal. But this should not be your go-to medication for sleep every night… because you’re gonna want to prevent long-term complications.”
Your medicine cabinet might be well-stocked—but your health deserves thoughtful choices. It’s not about fear, it’s about awareness. After all, the best health advice often sounds simple: use with care, read the label, and ask questions.
