Perception of Tramadol as "Safer" May be Inaccurate

A recent study from the Mayo Clinic has found that tramadol may not be the safer, low-risk opioid that many consider it.

Investigators found that, despite it being listed as a schedule IV drug in the US, tramadol was linked to a greater risk of prolonged use following surgery than other common opioids.

"This data will force us to reevaluate our postsurgical prescribing guidelines," says lead author Cornelius Thiels, DO, a general surgery resident in Mayo Clinic School of Graduate Medical Education. "And while tramadol may still be an acceptable option for some patients, our data suggests we should be as cautious with tramadol as we are with other short-acting opioids."

Investigators sought to determine the risk of transitioning from acute to prolonged use in opiate-naïve patients treated for postoperative pain using tramadol. They conducted a retrospective analysis of claims data from the Optum Labs Data Warehouse and identified a population of 524,318 for inclusion in their study.

Patients were excluded if they had multiple unrelated procedures on the same day, those with an inpatient stay longer than 7 days, those admitted as an inpatient more than one day before surgery, patients receiving non-cancer surgeries if they had cancer, and any patients receiving hospice services. They also did not include any patients who had a stay in a skilled nursing facility within a day of discharge.

All patients underwent 1 of 20 commonly performed surgeries between Jan. 1, 2009 and June 30, 2018. The surgeries were chosen with the aim of including common inpatient and outpatient procedures form multiple specialties and spanning differing degrees of expected postoperative pain.

Of the 524,318, 444,764 had at least 180 uncensored days of follow-up and 357,884 of them had a discharge prescription for 1 or more opioids. Just 3% (13,519) received tramadol alone and 1.2% (5457) received tramadol with another short-acting opioid. Authors noted that women were more likely to receive tramadol (62.1% of tramadol alone versus 49% of total cohort).

Investigators noted that larger discharge prescriptions were associated with a higher risk of prolonged opioid use across all definitions of prolonged use. Receiving 500 morphine milligram equivalents was associated with nearly 5 times the risk of prolonged opioid use compared with the receipt of 1 to 199 milligram morphine equivalents using the consort definition of prolonged use and more than 6 times the risk of persistent use.

Receipt of tramadol was associated with increased adjusted risk across all definitions of prolonged opioid use. The receipt of tramadol alone was associated with a 6% increase in risk of additional opioid use relative to people receiving other short-acting opioids, a 47% increase in the adjust risk of persistent use, and a 41% increase in the adjusted risk of a CONSORT chronic use episode.

Within their conclusion, authors wrote the study shows that, while tramadol is considered a schedule IV it has a similar or somewhat greater risk of prolonged opioid use after surgery as some schedule II drugs such as hydrocodone and oxycodone. Authors suggest that, the Drug Enforcement Administration and the US Food and Drug Administration should consider rescheduling tramadol to a level that reflects its risks of prolonged use.

"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," says senior author Molly Jeffery, PhD, the scientific director of research for the Mayo Clinic Division of Emergency Medicine.

This study, titled “Chronic use of tramadol after acute pain episode: cohort study,” is published in BMJ.