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Reader question on OTC pain relievers generates thorough, evidence-based response


Welcome to Dear Julia, a weekly column where readers can submit everyday health questions on anything from the science of hangovers to the mysteries of back pain. Julia Belluz will sift through the research and consult with experts in the field to figure out how science can help us live happier and healthier lives.

Have a question? Use our submission form or ask @juliaoftoronto on Twitter.

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 asurgery, a cut, or a burn, but his message was simple: Ibuprofen seems to work best, followed by acetaminophen, and then aspirin.

lowback pain jb


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.


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.)


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. There’s also some evidence that NSAIDS may increase the risk of psychosis and cognitive impairment in the elderly, so doctors may avoid prescribing them for older 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.

Send your questions to Julia via the submission form or @juliaoftoronto on Twitter. Read more about Dear Julia here.


5 Star


Should you take Tylenol, Advil, or aspirin for pain? Here's what the evidence says.

Our Review Summary

IbuprofenIn this installment of “Dear Julia,” Vox health reporter Julia Belluz takes on a reader question about pain medications. The reader wants to know which over-the-counter (OTC) pain reliever is the best for treating pain – Tylenol, Advil or aspirin. The story presents evidence from high-quality studies and opinions from three pain experts. The story carefully explains that it’s not appropriate to state unequivocally that one beats the other because it’s not a one-size-fits all situation. In general, though, ibuprofen (name brand Advil) is more effective and safer than acetaminophen (Tylenol) and aspirin in beating minor pain.

The “Dear Julia” column, which debuted earlier this month, promises to answer “everyday health questions on anything from the science of hangovers to the mysteries of back pain.” The column is off to an auspicious start, and we look forward to more of its practical, evidence-based responses. You can submit a question for the column here.


Why This Matters

Americans spent $4.4 billion on OTC analgesics in 2014, according to the Consumer Healthcare Products Association. Despite wide use and efforts by public health efforts to inform consumers about safety issues, there’s still a lot of confusion about which medication works best for different ailments. As the article points out, acetaminophen is the most popular selling OTC pain reliever but not always the most effective or safest.


Does the story adequately discuss the costs of the intervention?

Not Applicable

The story doesn’t mention costs but since these over-the-counter medications have been widely available for a long time it doesn’t seem like an important omission. Because aspirin has been available the longest and is manufactured by literally hundreds of companies, it is by far the cheaper of the three.

Does the story adequately quantify the benefits of the treatment/test/product/procedure?


The article takes a close look at the drawbacks and benefits of each drug. For example, while the experts said acetaminophen is less effective than ibuprofen in treating pain (and carries more risks than the others), it is beneficial in treating fever, especially in children age three and up. Ibuprofen is deemed less toxic for pain relief but it carries the risk of bleeding in the gastrointestinal tract and kidney damage. There’s also a reasonable amount of quantification provided by an expert source, Dr. Andrew Moore, who says: “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.” The story would have been even stronger had it provided links or additional details regarding where this expert obtained his estimates.

Does the story adequately explain/quantify the harms of the intervention?


The story comprehensively describes the harms from each drug based on different uses and patient populations. We especially liked this quote: Don’t believe that just because something is over-the-counter, it’s safe.”

Does the story seem to grasp the quality of the evidence?


The story cites and links to reliable evidence sources, including a systematic review of randomized controlled trials on back pain published in the BMJ.

Does the story commit disease-mongering?


There are no examples of disease mongering in the story.

Does the story use independent sources and identify conflicts of interest?


Sourcing is a very strong component of the article. The story quotes three pain experts from three different institutions as sources. No conflicts of interest were apparent.

Does the story compare the new approach with existing alternatives?


The main premise of the story was comparing which pain medication was the best for different types of pain. The comparisons are covered in depth with perspectives from three sources.

Does the story establish the availability of the treatment/test/product/procedure?


It’s obvious from the story that all of the medications profiled have been widely available without a prescription for many decades. Aspirin, a modified version of salicyclic acid, was created by a Bayer chemist in 1897; acetaminophen followed in 1956; and ibuprofen in 1962.

Does the story establish the true novelty of the approach?


The story establishes that it’s responding to a reader question about three well-known and widely used medications. It also notes the gap between public perception about these drugs and what pain researchers think of them.

Does the story appear to rely solely or largely on a news release?


Since this article was prompted by a reader question and includes comments from three expert sources, we are confident it isn’t based on a news release.

Total Score: 9 of 9 Satisfactory

Comments (2)

Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.

Mark Schoene

August 31, 2015 at 8:44 am

Don’t think the VOX article deserves such a high score. It contains some factual errors. And the message that ibuprofen is the “go-to” drug for treating minor pain is certainly open to question (at least in the back pain area)—and conflicts with the recommendations in many evidence-based guidelines.

The article mischaracterized the BMJ review (Machado, 2015) it used as one of its evidence anchors. “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.”, according to the VOX article.

The evidence on acetaminophen for back pain in that review pertains only to acute back pain (coming largely from a single RCT), not chronic. The only RCT to ever look at acetaminophen for chronic back pain (Wetzel, 2014) was included in that review—but has been retracted. (

The vast majority of international guidelines on low back pain don’t recommend NSAIDs, or ibuprofen in particular, as the analgesic(s) of first choice for low back pain. Most recommend acetaminophen because of its safety profile. (Koes, Eur Spine J. 2010 Dec; 19(12): 2075–2094.)

The 2007 American College of Physicians/American Pain Society review (Chou, Annals of Int Med, 2007) on medications for low back pain offered what might be the best conclusion about choice of analgesics for pain: “Evidence is insufficient to identify one medication as offering a clear overall net advantage because of complex tradeoffs between benefits and harms. Individual patients are likely to differ in how they weigh potential benefits, harms, and costs of various medications.”

Mark Schoene
Editor, BackLetter
Consumer Representative, Cochrane Back and Neck


    Julia Belluz

    September 2, 2015 at 8:08 am

    Mark, thank you for your comments. Yes, that the BMJ review mainly looked at evidence for acute low back pain, but the evidence on these drugs for chronic pain is limited and some of the guidelines you cite are out of date and not reflective of the latest research. I ran your comments by the researchers I spoke to as well as Roger Chou (who you cite here) and they agreed the conclusions I drew were correct based on the latest research — that ibuprofen appears to be more effective. Still, I have added some notes in the piece that should clarify that limitation on the BMJ study. In any case, thank you for taking the time to comment and feel free to email me if you have any further remarks.