NSAIDs vs. acetaminophen: What you need to know before your next headache

Fox News

18-06-2025

Most households have a stash of painkillers tucked away for surprise headaches or stubborn cramps.
But some may not realize that all painkillers are not created equal, and they don't all treat the same kind of pain.
Over-the-counter (OTC) pain relievers fall into two main categories, according to MedLine Plus.
The first is NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen and naproxen.
"These reduce both pain and inflammation, but can irritate the stomach if not taken with food," Dr. Jessica Oswald, MD, MPH, an anesthesiologist and pain management specialist at UC San Diego Health, told Fox News Digital.
The other medication, acetaminophen, also helps with pain and fever, but does not reduce inflammation, Oswald noted.
Dr. Min "Frank" Wu, a physician at AdventHealth in Littleton, Colorado, elaborated on how these drugs work differently in the body.
NSAIDs are effective in treating fever and pain relief, the doctor told Fox News Digital.
These medications can alleviate a variety of symptoms related to arthritis, infection, back injury, headaches and muscle strain, along with other acute and chronic conditions that cause pain and inflammation, he said.
"NSAIDs work by inhibiting cyclooxygenase enzymes (COX-1 and COX-2) throughout the body," he noted, which means they inhibit the production of "biological mediators" that cause inflammation and blood clotting.
Acetaminophen, on the other hand, works by "inhibiting COX enzymes and modulating the endocannabinoid system in the central nervous system (brain and spinal cord) to exert its effects," Wu said.
As a pain reliever, acetaminophen is effective for migraines, according to the doctor.
"In combination, acetaminophen/caffeine is recommended as a first-line agent by many European agencies," he noted.
Acetaminophen's effectiveness for arthritic pain, however, is small and not clinically important, according to Wu.
"It has not been shown to be effective for low back pain or radicular (nerve pain) in general," he added.
Wu pointed out that acetaminophen appears to boost the pain-relief properties of other medications.
"The combination of acetaminophen and NSAIDs has been shown to be more effective than either medication alone," Wu said.
Oswald also spoke about this method, which she calls a "multimodal" approach.
"In many cases, combining different types of pain relievers can be more effective than using just one," she told Fox News Digital.
For example, an NSAID like ibuprofen along with acetaminophen and a topical cream "can work together to relieve pain more effectively," Oswald said.
Research has shown that NSAIDs have multiple adverse effects and should be used with caution, both doctors pointed out.
"They have been shown to cause gastrointestinal issues, and in severe cases can cause ulcers and bleeding," Wu noted.
These side effects appear to be dependent on the size of the dose, the doctor added.
"In many cases, combining different types of pain relievers can be more effective than using just one."
There is evidence of increased gastric effects, kidney impairment and heart disease at higher doses. The U.S. Food and Drug Administration (FDA) has also issued warnings about cardiovascular risk.
At high enough doses, it can (less commonly) cause liver damage, which can potentially be fatal, according to Wu.
Oswald recommended that people with certain health conditions — such as kidney problems, heart issues or stomach ulcers — should talk to a doctor before using NSAIDs.
Acetaminophen has been linked to a potential risk of liver injury and allergic reactions, according to the FDA. Rare but serious skin reactions have also been reported.
"Acetaminophen is generally safer for most people, as long as they stay under 3,000 milligrams per day," Oswald added.
After weighing the benefits and risks, the doctor said that people should "absolutely" keep both types of OTC medications on hand at home.
"Having a few different options allows you to manage pain more effectively by targeting it in different ways," she said.
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Ultimately, if pain doesn't improve or keeps coming back, it's best to consult a healthcare professional who can assess the cause and discuss other treatment options, including prescription medications.