Mayo Clinic Investigates: Is Tramadol Safe?

According to new research performed by Mayo Clinic, the historically “safer” synthetic Opioid Tramadol poses the same high risk for prolonged use, just like any of the other most common prescription Opioid medications. The Drug Enforcement Administration (DEA) currently classifies Tramadol as a Schedule IV drug, which means it’s considered to have a lower risk of addiction and abuse than Schedule II Opioids, such as Vicodin® and Oxycodone. However, new research that emerged last week from Mayo may result in the re-classification of the drug.

The Study and Results

For years, many have considered Tramadol to be one of the safest Opioids on the market. In clinical trials the drug seemed to offer all the pain-numbing benefits of stronger and more addictive drugs, with the added bonus of producing fewer dependency rates. The majority of these clinical trials examined Tramadol use by injection, rather than the commonly prescribed pill form – which has been proven to be much more potent. Tramadol has since become widely prescribed and accepted by physicians as a safer alternative for pain. Over the past ten years, however, emergency room departments have reported a growing number of visits for Tramadol-related overdoses and withdrawal, prompting some to question the true nature and safety of the drug.

Researchers at Mayo Clinic sought to provide answers by investigating the addictive potential of Tramadol for users. The Mayo team of physicians and researchers used the OptumLabs Data Warehouse to examine the records of 444,764 patients that underwent 20 common surgeries across the U.S. between Jan. 1, 2009, and June 30, 2018.The team found that 357,884 patients of those procedures filled a prescription for Opioids after surgery.

It was found that among those with a prescription:
  • 7% had at least one refill 90-180 days after surgery, which was defined by the team as additional use.
  • 1% refilled their prescription 180-270 days after surgery, which was defined as persistent use.
  • 0.5% had 10 or more prescription fills or 120 or more days’ supply, which was defined as long-term use.

Also, the team notably discovered that patients in all three categories were more likely to have received a prescription for Tramadol.

Senior author Molly Jeffrey, Ph.D., the scientific director of research for the Mayo Clinic Division of Emergency Medicine, draws attention to the contradicting nature of the DEA’s classification of the drug based on the study results.

“We found that people who got Tramadol were just as likely as people who got Hydrocodone or Oxycodone to continue using Opioids past the point where their surgery pain would have been expected to be resolved,” she said. “This doesn’t tie to the idea that Tramadol is less habit forming than other Opioids.”

What This Means for Tramadol and the DEA

The findings of the study suggest that additional dialogue is needed on the drug’s treatment by the DEA. Researchers found that Tramadol use has been increasing over the study period, and at 4%, it was the third most-prescribed Opioid in the study. Hydrocodone was prescribed the most at 51%, followed by Oxycodone at 38%.

Given that Tramadol is not as tightly regulated as other short-acting Opioids, these findings warrant attention.

Despite its reputation as being a “safe pain medication,” Tramadol is still an Opioid and has the potential for abuse and addiction. Researchers are pushing for Tramadol to be reexamined by the DEA and possibly re-classified as a Schedule II drug similar to other Opioids. The Mayo Clinic team also hopes that the results of the study will encourage physicians to reevaluate Tramadol post-surgical prescribing practices and question if patients truly need an Opioid prescription after surgery.

Author: Jena Hilliard – Last Edited: June 17, 2021


Science Daily. (2019). Historically “Safer” Tramadol More Likely Than Other Opioids to Result in Prolonged Use. Retrieved on 20th May 2019 from