It Takes Two Paracetamol?
Note: Depending on where you live paracetamol is also known as acetaminophen, APAP and Tylenol.
I have had a version of the following conversation a surprising number of times:
“I have a headache.”
“Aah, that sucks. Did you take some paracetamol?”
“Yes, but it still hurts.”
“How many did you take?”
The fact that I even ask this question is because I have been noticing a trend.
“One.”
“You should take two, it makes a big difference.”
“Nah, I’m fine with one.”
“But you still have a headache.”
“Yeah, but it doesn’t make much of a difference. Paracetamol just doesn’t work that well for me.”
Everyone is free to choose how many paracetamol they take, but I’ve always had this hunch that there is a big difference between taking one or two paracetamol. Where taking one has almost no effect on my headaches, but taking two makes a big difference. Effectively I’m making two claims:
1000mg paracetamol works better than 500mg paracetamol.
500mg paracetamol doesn’t work much better than placebo.
Today I chose to finally resolve this mystery and laugh in the face of my friends! Or I will admit in shame that I was wrong...
Claim 2: 500mg vs placebo
There is a Cochrane Review from 2016 that tries to answer exactly my question.[1] The review looks at pain relief with paracetamol for tension-type headaches, the most common form of headaches. They reference two studies that have compared 500mg/650mg with placebo that also fit their inclusion criteria.
Steiner 2003[2], which comes to the following conclusion:
They didn’t find a significant result when comparing 500mg paracetamol and placebo! But they did find a significant result when comparing 1000mg paracetamol and placebo.
Dahlöf 1996 is less conclusive. This study only contains 29 participants, where only 14 of them took paracetamol at a dose of 500mg.
In this study both 500mg and 1000mg performed equally well, but with the low participant numbers it is hard to draw any conclusions.
The Cochraine Review itself comes to the conclusion that they couldn’t find a significant difference between 500mg paracetamol and placebo, but that the quality of evidence is low.
Claim 1: 1000mg vs 500mg
The same Cochrane Review concludes that a 1000mg paracetamol outperforms placebo. There is high quality evidence for this being the case when looking at
Pain-free at two hours: the proportion of attacks/participants who were pain-free at two hours with paracetamol.
Pain-free or mild pain at two hours: the proportion of attacks/participants who were pain-free or had only mild pain at two hours with paracetamol.
There is moderate quality evidence for this being the case when looking at
Pain-free at one hour: The proportion of attacks/participants who were pain-free or had only mild pain at one hour with paracetamol.
Pain-free at four hours: The proportion of attacks/participants who were pain-free at four hours with paracetamol.
Although it might seem that I’m moving towards a clear win for my case, I’m afraid I have to highlight one interesting point which is exemplified by the work of Steiner 2003[2].
Their data leads to three seemingly incompatible statements:
They find a significant difference between 1000mg paracetamol and placebo.
They don’t find a significant difference between 500mg paracetamol and placebo.
They don’t find a significant difference between 500mg and 1000mg paracetamol.
It is funny that these three statements can all true at the same time. At this point in time we don’t have the data to show that a 1000mg outperforms 500mg.
Conclusion
To be honest, I didn’t expect the results I found. In hindsight it is obvious that these statements can all be true at the same time, but when starting out I hadn’t considered it an option.
I think I can safely say the following going forward:
Take two paracetamol, there is good evidence that it will help you with your headache.
You can take one paracetamol, but we simply don’t know if it works.
Edits: I have edited this post quite intensively based on the comment of Lao Mein. They correctly spotted that one of the journals I quoted from, Open Pain Journal, has an impact factor of 0.11. I have removed this reference and I’ve based the article fully on the Cochrane Review.
- ^
Stephens, G., Derry, S., & Moore, R. A. (2016). Paracetamol (acetaminophen) for acute treatment of episodic tension‐type headache in adults. Cochrane Database of Systematic Reviews, (6).
- ^
Steiner, T. J., Lange, R., & Voelker, M. (2003). Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol. Cephalalgia, 23(1), 59-66.
- ^
Gaul, C., & Eschalier, A. (2018). Dose Can Help to Achieve Effective Pain Relief for Acute Mild to Moderate Pain with Over-the-Counter Paracetamol. The Open Pain Journal, 11(1).
Anecdotally, higher doses result in less pain for me, too. But, I’d caution anyone who was chronic migraines, or any sort of chronic pain, to limit themselves to a few standard doses a week. My doctors kept telling me that I likely had Medication overuse headaches, and I kept going “no way, I don’t take that much, and I’ve had regular headaches before taking my current regiment.” Finally, after years of prompting, I toughed out three weeks with no medication and my severe migraines were reduced in duration afterwards. Please be very careful of this slippery slope.
I’m usually not the type of guy to dunk on a journal for having low impact factor but uh...
Impact-factor 0 journals are a really really bad sign. An extremely bad sign. I wouldn’t recommend taking it seriously at all. It’s like a limbo for damned papers that were rejected from every other publication. You see things in there. Things you can’t forget. Entire plagiarized papers that were Google translated to Chinese and then back to English. That internet meme where some guy literally put “T” on top of his bar plot instead of real error bars. Forgetting to correct for multiple hypotheses. Unforgivable sins.
My best recommendation is to look for a higher-quality source.
Thank you for your feedback! This is a mistake on my part. I will take the article down until I’ve looked into this and have updates my resources.
Edit: I have updated the article. It should be better now :)
I use ibuprofen almost exclusively because a source I trusted told me years ago that it was better for me longterm than acetaminophen (alas I have no idea what the source was) but I think the same principle applies. I always take one pill to start because I worry about developing tolerance / rebound headaches / kidney damage / stomach upset, and then if that doesn’t seem to make a difference within 60-90 minutes, I take a second one. I find that usually I need two (i.e. the recommended dose), perhaps since I only take painkillers at all when the pain has risen beyond a certain level, but sometimes one is sufficient.
I realize this isn’t actually evidence that a half-dose is at all distinguishable from placebo, but the point is, if you worry about overuse like I do (e.g. because you have a chronic condition), I see no reason to not just take one pill to start. If it alleviates your pain, then great, if not, you can take another.
I get a lot of headaches, and for a while had the cached belief that ibuprofen was the way to go and acetaminophen (paracetemol) doesn’t work on me at all. But after a c-section I was given the big doses of both, and told to alternate, and I noticed that I could definitely tell the difference between skipping/delaying an acetaminophen and taking it on time. So now I use that for headaches, especially sinus-y headaches where I don’t want to suppress my immune response that’s trying to get my cold to go away.
1 000 mg is the standard dose in France, with 500mg being used almost only for children.
Interesting. I didn’t know that anyone ever took just one paraceatamol. In the UK the packets all say that the dosage is two tablets, unless you are a small child. So people just kind of follow the instructions (at least I do). I have migraines infrequently (once a month, slightly less) but when I do realise I am having a migraine their is no way I am taking any paraceatamol less than what the packet stipulates. Firstly because I am in pain, and secondly because migraines seem to fog up by basic cognition in weird ways—I get weirdly stubborn about following instructions. Imagine me there, my vision swimming, can’t read because my sight is blury and the room is spinning. But the box says to “Always read the instructions in full before use” so I have to read this tiny text on this little paper before I can have my paracetamols. So when the instructions tell me 2, that is what it shall be. (I now throw the instructions away while sane).
In my country it says to take 1-2 paracetamol, so that might be the cause of the confusion.
In the hospital, we usually give 1g IV for any real pain. I don’t think the notion that giving more of a painkiller would produce a stronger effect is particularly controversial!
(Anecdotally, the IV route is somewhat more effective, even though the nominal bioavailability is the same as the oral route. It might be down to faster onset and the placebo aspect of assuming anything given by a drip is “stronger”)
In the hospital, we usually give 1g IV for any real pain. I don’t think the notion that giving more of a painkiller would produce a stronger effect is particularly controversial!
(Anecdotally, the IV route is somewhat more effective, even though the nominal bioavailability is the same as the oral route. It might be down to faster onset and the placebo aspect of assuming anything given by a drip is “stronger”)