by Julia Belluz     August 18, 2015   @juliaoftoronto    julia.belluz@voxmedia.com

What’s the difference between Tylenol, Advil, and aspirin? Which is the best to take for pain?

I used to take acetaminophen (usually referred to by its brand name, Tylenol) for the occasional headache or sore muscle, mostly because that’s what we used in my house growing up. I didn’t think much about whether it was more or less effective than any other type of over-the-counter pain reliever, and I suspect the same is true for many folks. Acetaminophen, after all, is the most popular over-the-counter painkiller worldwide.

So I was surprised when I found out there’s a huge gap between how pain researchers think about this drug and how the public does. More specifically, every researcher I contacted for this piece said some variation of what Andrew Moore, a pain researcher at Oxford University, told me: Tylenol doesn’t actually work that well for pain. To be more exact, “I can’t imagine why anybody would take acetaminophen,” he said.

Moore has done a number of systematic reviews on over-the-counter pain medications, looking at all the available evidence to figure out which ones work best for various problems. I asked him to describe the overall success rates for the most common three: acetaminophen (like Tylenol), ibuprofen (like Advil), and aspirin.

Like all good evidence-based medicine thinkers, he was able to provide a very practical answer: “If you’re talking about aspirin in doses of 500 to 1,000 mg or two tablets, 30 percent of people get relief from acute pain. For acetaminophen at doses of 500 to 1,000 mg, about 40 percent have a success. For ibuprofen, in its normal formulation at something around 400 mg or two tablets, about 50 percent have success.”

Now, Moore was referring here to acute pain that strikes after a specific event, like a surgery, a cut, or a burn, but his message was simple: Ibuprofen seems to work best, followed by acetaminophen, and then aspirin.

For ongoing (or chronic) pain — a sore lower back, say, or the kind of degenerative arthritis that typically develops with age — ibuprofen still outperforms acetaminophen. In fact, study after study has shown that acetaminophen on its own just doesn’t work that well for most people to treat this kind of pain, either.

“WE FOUND THAT [TYLENOL] IS INEFFECTIVE ON BOTH PAIN AND DISABILITY OUTCOMES FOR LOW BACK PAIN”

A 2015 systematic review of high-quality evidence, published in the BMJ, found that acetaminophen didn’t seem to help most sufferers of chronic low back pain, and that it barely alleviates pain in people with osteoarthritis. As the researchers wrote, “We found that [acetaminophen] is ineffective on both pain and disability outcomes for low back pain in the immediate and short term and is not clinically superior to placebo on both pain and disability outcomes for osteoarthritis.”

They also noted that patients on acetaminophen “are nearly four times more likely to have abnormal results on liver function tests compared with those taking oral placebo.”

Other studies, like this well-designed randomized control trial of people with knee pain, have similar conclusions: Acetaminophen doesn’t perform as well as ibuprofen, and it’s linked to higher rates of liver problems.

So what about the occasional headache? What works best for that?

It turns out this is another fascinating problem area for pain researchers. Moore has looked at all the evidence for what he calls “infrequent tension headaches” and found “it is surprising how poor [the research] is and how little it tells us.” Either the outcomes in studies are badly defined, the studies have too few participants to say anything concrete, or many people in the studies actually seem to have chronic headaches as opposed to the ordinary ones they’re allegedly studying.

“Most people would say, if you look at the data, take an ibuprofen tablet,” Moore said. “Acetaminophen is just not a very good analgesic [pain reliever], yet it’s the go-to drug because it’s thought to be safe.”

And that’s where things get even more interesting: Acetaminophen isn’t actually that safe.

“We always thought [acetaminophen] was safe, but there are increasing signals of accidental overdose in people who are regularly using it for chronic pain, and some liver toxicity,” explained the University of Leeds’s Philip Conaghan, who has studied adverse events data related to this popular drug.

Between 1998 and 2003, acetaminophen was the leading cause of acute liver failure in the US. There are also hundreds of related deaths every year — though keep in mind that millions of people take drugs with acetaminophen, so these more extreme side effects are rare (especially if you’re only taking them in small doses occasionally). Still, for the drug’s minimal pain-killing benefits, the risks may not be worth it.

“Don’t believe that just because something is over-the-counter, it’s safe,” Conaghan added. (He advised people to see their doctor if they’re taking any of these painkillers for more than a few days — particularly if they’re on other drugs already.)

“[TYLENOL] IS AN OLD DRUG, OBSOLETE, AND SHOULD BE AVOIDED ALTOGETHER”

Kay Brune, a professor of pharmacology and toxicology at Germany’s Friedrich-Alexander University who has also studied the toxicity of painkillers, was even more direct in his thoughts on acetaminophen: “It’s an old drug, obsolete, and should be avoided altogether.”

Aspirin is safer than acetaminophen, he said, though to be used as a pain reliever it requires much higher doses — which can have side effects like stomach upset. Aspirin also interferes with blood coagulation for days after taking it. “If you take one gram of aspirin,” Brune explained, “you’re at risk of bleeding for another four days.” This is why aspirin has its place as a protective agent against strokes and heart attacks for people at a higher risk.

Ibuprofen doesn’t have these two problems — it’s less toxic than the others in the doses that give people pain relief. But it has other side effects. “Ibuprofen puts people at risk of bleeds in the gastrointestinal tract and kidney damage — so it’s not free of risk,” said Brune. Using it in high doses also seems to raise blood pressure, and increase the risk of heart attack and stroke — one reason the Food and Drug Administration recently warned people should only use ibuprofen (and other “Nonsteroidal anti-inflammatory drugs” or “NSAIDS” like naproxen) for short periods of time and in small amounts.

I asked Brune about what he’d suggest for the occasional headache or sore muscle. “Taking 400 mg of ibuprofen won’t cause measurable harm,” he answered. “Of all drugs we have available, for most indications, it’s also the most effective one.”

If the research community seems to have sided with ibuprofen for pain, is acetaminophen good for anything?

Patients with kidney and cardiovascular problems may need to avoid NSAIDS like ibuprofen, so doctors could suggest Tylenol here even though it probably won’t provide as much pain relief. NSAIDS can also cause psychosis and cognitive impairment, so doctors may avoid prescribing them for elderly patients.

Fever is another area where acetaminophen can help, said Moore. According to one systematic review, acetaminophen seems to be safe for treating very young kids with fever, and you can give children as young as 3 months old acetaminophen, whereas you need to wait until kids are at least 6 months old to safely treat them with ibuprofen. (Aspirin is not recommended for anyone under 18 years old since it can cause a potentially fatal condition called Reye syndrome.) This may help to explain the popularity of drugs like Tylenol for kids.

But a final caveat here: If your child is older than 6 months, it’s not all that clear that acetaminophen outperforms ibuprofen for reducing fevers, and the same is true for adults. So keep that in mind when you’re rethinking your medicine cabinet.