Over-the-counter pain relievers outperform opioids after wisdom tooth extraction

Over-the-counter pain medications work as well or better than opioids after wisdom tooth extraction for both men and women, according to a Rutgers Health-led follow-up to a landmark paper on comparative pain relief.

That first paper on the collective experience of more than 1,800 trial patients found that the combination of ibuprofen and acetaminophen provided better pain relief than hydrocodone with acetaminophen for the first two days after surgery and greater satisfaction over the post-operative period. The new subgroup analysis, published in JAMA Network Open, demonstrated that the results held for both male and female patients.

We wanted to determine whether the pain medication's effects were consistent in males and females separately. And what we found is that in both subgroups (males and females), the non-opioid was superior for that first day and night, and then no worse than the opioid for the rest of the post-op period."

Janine Fredericks Younger, associate professor at Rutgers School of Dental Medicine and lead author of the analysis

The trial that produced both papers, funded by an $11 million grant from the National Institutes of Health, compared patients who received 400 milligrams of ibuprofen (Advil, Motrin) combined with 500 milligrams of acetaminophen (Tylenol) against those who got 5 milligrams of hydrocodone with acetaminophen. 

The gender-specific analysis was particularly important because women consistently report higher pain levels after surgery, raising questions about whether pain medications work differently for each sex. 

"There's obviously different biological mechanisms, different hormones involved," said Cecile Feldman, dean of Rutgers School of Dental Medicine and senior author of both studies. "But results confirm that the analgesic effect for both groups is the same."

The researchers deliberately enrolled equal numbers of men and women from the start, allowing them to conduct robust subgroup analyses. Patients across five universities tracked their pain twice daily for nine days using electronic diaries, rating not just pain but also sleep quality, ability to perform daily activities and overall satisfaction.

On every measure, the over-the-counter combination matched or beat the opioid. Patients taking the non-opioid medications reported better sleep quality and less interference with daily activities. Those who received opioids were twice as likely to call back requesting additional pain medication.

"The results actually came in even stronger than we thought they would," Feldman said. "We expected to find the non-opioid to be non-inferior, so that at least it was no worse than opioids. We were surprised to see that it was actually superior."

Dental procedures are a common entry point for opioid exposure. Dentists wrote more than 8.9 million opioid prescriptions in 2022, ranking among the nation's leading prescribers of the drugs.

"There are studies out there to show that when young people get introduced to opioids, as many have via wisdom tooth extraction, there's an increased likelihood that they'll eventually use them again, and then it can lead to addiction," said Fredericks Younger, noting that opioid overdoses kill more than 80,000 Americans annually.

The research focused on the extraction of impacted wisdom teeth, which requires cutting into gums and sometimes removing bone, making it one of the most painful dental procedures. The Food and Drug Administration uses this as a standard model for testing pain medications because it reliably produces moderate to severe pain for about 48 hours.

Feldman said the results, showing the superiority of the over-the-counter medication to opioids, likely apply to other dental procedures but cannot be automatically generalized to surgeries in other parts of the body. She would like to see similar studies conducted for a range of procedures, particularly those for orthopedic injuries, which frequently result in opioid prescriptions for high school and college athletes.

Despite mounting evidence, many dentists continue writing "just in case" opioid prescriptions for patients who are told to start with over-the-counter medications. The next phase of research will examine why these prescribing patterns persist.

"How can we now, with the evidence and the knowledge that we have, eliminate these prescriptions from being written?" Fredericks Younger said.

The findings align with American Dental Association recommendations to avoid opioids as first-line pain treatment. Feldman said the study's results leave little room for doubt.

"We feel pretty confident in saying that opioids should not be prescribed routinely for dental procedures," she said. "Our non-opioid combination really should be the analgesic choice."

Source:
Journal reference:

Fredericks-Younger, J., et al. (2025). Analgesic Differences in Males and Females After Third Molar Surgery. JAMA Network Open. doi: 10.1001/jamanetworkopen.2025.42467. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2841046

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