Little Evidence to Support Rescheduling of Tramadol

By Roger Chriss, PNN Columnist

The consumer watchdog group Public Citizen has petitioned the FDA and DEA to “upschedule” the opioid painkiller tramadol. The DEA set tramadol as a Schedule IV drug in 2014, and the petition urges moving it to a more restrictive Schedule II, on the same risk level as hydrocodone and oxycodone.

The petition claims that tramadol is “an increasingly overprescribed, addictive, potentially deadly narcotic.” But the basis for this claim and the assumption that upscheduling will help are problematic.

The CDC reports that there were approximately 1,250 fatal overdoses involving tramadol in 2017, the most recent year for which data is available. Like most fatal overdoses, tramadol deaths often involve multiple drugs, so it’s hard to draw any conclusions from those deaths.

Tramadol is complex, with a highly variable patient response. Some patients have such a strong negative reaction to the drug that they refuse to take it again. Others find it too sedating at high doses or too weak to provide adequate pain relief. Abuse, addiction and overdose can also occur with tramadol.

Recently Harvard Health looked at a JAMA study on the risks of using tramadol versus other pain relievers. Tramadol was found to have a higher risk of death than anti-inflammatory medications such as naproxen (Aleve), while people treated with codeine had a similar level of risk.

“However, because of the study’s design, the researchers could not determine whether tramadol treatment actually caused the higher rates of death. In fact, the patients for whom tramadol is prescribed could make it look riskier than it truly is,” said Robert Shmerling, MD, an editor at Harvard Health.

Unintended Effects of Upscheduling

Understanding the effects of upscheduling is tricky. In 2014 the DEA reclassified hydrocodone (Vicodin) from Schedule III to the more restrictive Schedule II. The reclassification accelerated a trend that was already underway – hydrocodone prescriptions had been falling since 2011.

But there were unintended consequences to upscheduling. A recent University of Texas study found that decreases in hydrocodone prescribing after its rescheduling “were larger in patients being treated for cancer.”

Anotherr study found that upscheduling led to a substantial decrease in hydrocodone prescribing in hospital emergency departments, but that was offset by an increase in prescriptions for codeine and anti-inflammatory drugs.

Upscheduling hydrocodone has also had a negligible effect on overdoses, which are largely caused by illicit fentanyl, heroin and other street drugs, as well as non-opioid medications such as Xanax.

Similarly, predicting the impact of new prescription opioids is difficult. Breathless warnings about the opioid Zohydro, which was approved as a Schedule II drug in 2014, proved false. “There was no great surge of overdoses” after Zohydro was introduced, as Chris MacGreal wrote in his book “American Overdose.”

Fears about opioids are also delaying the introduction of safer medications. The experimental opioid NKTR-181 has less abuse potential than traditional opioids, but its approval is uncertain because the FDA has stopped all advisory committee meetings on opioid analgesics.

Public Citizen ignores all this. It also fails to mention other actions the FDA could pursue, from making naloxone into an over-the-counter drug to improving access to medication-assisted therapy for opioid use disorder. There’s no petition to have the DEA “nix the wavier” for buprenorphine (Suboxone) to make it more widely available or to have the federal government promote the Pain Management Best Practices Inter-Agency Task Force report.

Finally, there’s no call to monitor outcomes. As PNN has reported, opioid tapering has had tragic unintended consequences. And a new Cochrane review on the effects of educational and regulatory efforts targeting prescribers was unable to draw any conclusions “because the evidence is of very low certainty.” The authors could find only two relevant studies that assessed prescribing policies adopted in the 1990’s.

There are good reasons to be cautious about tramadol. But there are probably better ways than upscheduling to reduce risks and improve outcomes. As a result, Public Citizen's petition seems quite narrow and unlikely to help with the overdose crisis.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

This column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Petition Urges DEA to Reschedule Tramadol

By Pat Anson, PNN Editor

In 2014, the U.S. Drug Enforcement Administration reclassified the opioid hydrocodone as a Schedule II controlled substance, citing evidence that the painkiller has a high potential for abuse and addiction. The change made it harder to obtain the drug and led to a sharp decline in hydrocodone prescriptions.

That same year, the opioid tramadol was classified for the first time as a Schedule IV drug – a less restrictive category that means it has low potential for abuse and addiction. Prescriptions for tramadol surged.

Five years later, a consumer watchdog group is saying that was a mistake. Public Citizen has filed a petition with the FDA and DEA asking that tramadol be reclassified as a Schedule II drug, on the same risk level as hydrocodone, oxycodone, morphine and fentanyl. The petition claims there is “overwhelming evidence” that tramadol is a public health risk, particularly for people who rapidly metabolize the drug.

“New evidence has accumulated showing that tramadol is an increasingly overprescribed, addictive, potentially deadly narcotic that should be rescheduled to Schedule II,” the petition states. “Tramadol’s current placement in Schedule IV has generated a false perception of the drug’s safety profile — particularly with respect to its potential for abuse, dependence, and addiction — among both prescribers and patients, which has contributed to the large increase in its prescribing following the DEA’s 2014 rescheduling of hydrocodone.”

Tramadol is considered a “weak” opioid because it does not bind directly to opioid receptors in the brain like hydrocodone and other opioids do. Many patients say tramadol gives them little or no pain relief, but it’s often the only opioid their doctor is willing to prescribe.

Tramadol is the active ingredient in several brand name painkillers such as Ultram, Ultracet, Ryzolt and Rybix. About 32 million prescriptions for tramadol were filled last year in the U.S.

“The failure to designate tramadol as a controlled substance when it was initially approved by the FDA and the subsequent placement of the drug in a less restrictive category has promoted the false belief that the drug must have a much better safety profile than other opioids,” Dr. Michael Carome, director of Public Citizen’s Health Research Group, said in a statement.

“The dangerous misperception of tramadol’s safety has led to reckless overprescribing of the drug during the past several years of the opioid epidemic.”

According to government health surveys, tramadol was misused by about 1.5 million people in 2018 – exceeding the number of people that misused morphine and some other Schedule II opioids.

In 2017, the FDA banned the use of tramadol in children under the age of 12, citing a handful of cases where children died or had serious breathing problems after using the drug.

A recent study by the Mayo Clinic found that patients given tramadol after surgery have a slightly higher risk of prolonged use than those receiving oxycodone or other short acting opioids.

Tramadol was classified as a Schedule 3 drug in the United Kingdom in 2014. It is still an unscheduled drug in Canada, although Health Canada has proposed classifying it as a Schedule I controlled drug.

Tramadol is widely abused in West, Central and North Africa.