Taken alone, acetaminophen is "not effective at any dose" for relieving pain or improving physical function for patients with osteoarthritis, concludes a large-scale meta-analysis recently published in The Lancet.
Dr. Sven Trelle, of the University of Bern in Switzerland, and colleagues found that acetaminophen - also known as paracetamol - was only marginally better than a placebo for treating symptoms of the degenerative joint disease.
Furthermore, the team found that the non-steroidal anti-inflammatory drug (NSAID) diclofenac was most effective for short-term pain relief from osteoarthritis, though the authors recommend against taking the medication long term due to its side effects.
Osteoarthritis is the most common form of arthritis, affecting an estimated 27 million Americans aged 25 and older, primarily those over the age of 65.
In osteoarthritis, the cartilage of the joints - the connective tissue that covers the end of the bones, acting as a cushion - breaks down, allowing the bones to rub together. This causes inflammation, stiffness and pain.
The hands, spine, knees and hips are the joints most commonly affected by osteoarthritis.
Acetaminophen and NSAIDs are considered a first-line treatment for relieving mild-to-moderate pain among patients with osteoarthritis, though Dr. Trelle and colleagues note that acetaminophen is more widely used in the long term because it poses fewer side effects than NSAIDs.
For their study, the researchers set out to determine which medications are most effective for treating osteoarthritis pain.
Acetaminophen 'showed no clinically important difference'
The researchers analyzed the data of 74 randomized trials conducted between 1980-2015 that included 58,556 patients with osteoarthritis.
Overall, the studies compared the effects of 22 different medications - including acetaminophen and seven different classes of NSAIDs - against a placebo, assessing how they affected patients' pain intensity and physical function at various doses.
All medications at all doses appeared to have beneficial effects in comparison with a placebo.
However, while some doses of paracetamol offered a slight improvement in pain intensity and physical function for patients, the effect did not reach the minimum standards of clinical effectiveness - defined as the smallest change in a treatment outcome that a patient would deem important.
In this study, the clinically important difference was -0.37, while treatment with acetaminophen only reached -0.17.
The NSAID diclofenac at a dose of 150 mg daily, however, was found to be most effective for reducing pain intensity and improving physical function, with a clinically important difference of -0.57. This effect was greater than that offered by maximum doses of other NSAIDs commonly used for the treatment of osteoarthritis, including ibuprofen, celecoxib and naproxen.
Commenting on their results, Dr. Trelle says:
"NSAIDs are usually only used to treat short-term episodes of pain in osteoarthritis, because the side effects are thought to outweigh the benefits when used longer term. Because of this, paracetamol is often prescribed to manage long-term pain instead of NSAIDs.
However, our results suggest that paracetamol at any dose is not effective in managing pain in osteoarthritis, but that certain NSAIDs are effective and can be used intermittently without paracetamol."
He adds that he hopes the findings will "better inform doctors about how to manage pain" in patients with osteoarthritis.
Patients may be 'suffering needlessly'
In an editorial linked to the study, Prof. Nicholas Moore, of the Department of Pharmacology at the University of Bordeaux, France, notes that there were a number of NSAIDs commonly used for the treatment of osteoarthritis that were not included in the meta-analysis, possibly because there have been no recent trials of such drugs or the trials that have been conducted are too small.
"These omissions are unfortunate because these drugs might be as effective but much cheaper than the newest drugs," he says.
Still, he believes the finding that acetaminophen is ineffective for the treatment of osteoarthritis is "remarkable," though perhaps unsurprising.
"Paracetamol has been on the market for as long as most of us remember. Its efficacy has never been properly established or quantified in chronic diseases, and is probably not as great as many would believe. Its safety is also questioned, not just in overdose," he adds.
"Many patients could be suffering needlessly because of perceived NSAIDs risks and paracetamol benefits (which might not be real). Perhaps researchers need to reassess both these perceptions (or misconceptions) and the use of other analgesic options that have been discarded over time, such as dipyrone."