Tramadol Banned by Anti-Doping Agency

By Pat Anson, PNN Editor

When it comes to treating pain, tramadol (Ultram) is widely seen as a weak synthetic opioid that provides little relief to patients with severe or chronic pain.

“I get a lot more relief from aspirin” and “this stuff does nothing but make you dizzy and sleep,” are some of the comments PNN readers have made about tramadol.  

But some professional athletes, particularly those in cycling, have a completely different take on tramadol. They use it as a performance enhancing drug that can help them run, skate or peddle faster, and for longer periods of time. That’s why the World Anti-Doping Agency (WADA) is adding tramadol to its list of prohibited drugs, starting in 2024.

“Tramadol has been on the WADA Monitoring Program for some years. Monitoring data has indicated significant use in sports including cycling, rugby and football,” WADA said in a statement. “Research studies funded by WADA have confirmed the potential for tramadol to enhance physical performance in sports.”

Results from one of those studies, recently published in the Journal of Applied Physiology, confirm many of WADA’s concerns. UK researchers enrolled 27 cyclists in a double-blind randomized study, in which they were given either 100mg tramadol or a placebo before engaging in 30 minutes of high intensity cycling, followed by a 25-mile time trial.

On average, the cyclists who took tramadol were 1.3% faster in the time trial (TT) than those given a placebo. That doesn’t sound like much, but in the highly competitive world of professional cycling, even a few seconds can be the difference between finishing first or second.

Interestingly, the researchers found there were “no differences in pain intensity” between the cyclists on tramadol and those who took the placebo.

“This study demonstrates that highly trained cyclists can maintain a significantly higher power output and complete a competitive TT in a significantly faster time following acute ingestion of 100 mg of fast-acting soluble tramadol. Tramadol reduced the perception of effort for a given power output but had no discernible impact on pain intensity whilst cycling,” wrote lead author Alexis Mauger, PhD, a professor in the School of Sport and Exercise Sciences at the University of Kent.

“The findings from this study suggest that tramadol elicits a significant performance-enhancing effect in highly trained cyclists, such that it can change the outcomes of a race. Given the evidence of the historical prevalence of use of tramadol in sport with the intention of improving performance, and the risks pertaining its use, this study provides strong evidence to justify its inclusion on the 2024 Prohibited Substance List.”

To be clear, no one is taking tramadol away from pain patients. But professional athletes who test positive for tramadol — without a medical reason for taking it — run the risk of suspension or disqualification if their sport follows the WADA guidelines..

Previous studies by Mauger found that acetaminophen (Tylenol) gave a 2% boost in performance for cyclists, suggesting that even a mild analgesic can be helpful in making endurance exercise seem easier. Conversely, it also lends weight to pain sufferers who say tramadol works no better than Tylenol or aspirin.      

“Now we have a conundrum. Tramadol, an opioid painkiller, appears to have had no effect whatsoever on the pain experienced during cycling. On the other hand, it significantly lowered the perception of effort, which in turn…  improved performance,” journalist Alex Hutchinson wrote in Outside. “I’m not sure what to make of this finding, but it reaffirms my sense that we still have a lot to learn about how pain and effort and other related constructs like mental fatigue influence our performance.”

The U.S. Food and Drug Administration classifies tramadol as a Schedule IV controlled substance, meaning it has less potential for abuse and addiction compared to opioids like oxycodone or hydrocodone, which are Schedule II drugs.

In recent years, prescriptions for tramadol have soared in the U.S. because it is considered “safer” than other opioids. In many third world countries, however, tramadol is widely misused. In 2019, Public Citizen filed an unsuccessful petition with the FDA to have tramadol reclassified as a Schedule II drug, saying there was “overwhelming evidence” that tramadol was a public health risk.

Abuse of Rx Opioid Painkillers Unchanged During Pandemic

By Pat Anson, PNN Editor

An alarming spike in U.S. overdose deaths during the COVID-19 pandemic does not appear to be fueled by increased abuse of opioid painkillers, according to a new nationwide analysis of urine drug tests.

The Drug Enforcement Administration approved an exemption last year allowing patients to connect with doctors via telehealth – without a physical examination -- to get prescriptions for opioids and other controlled substances. While the relaxed rules made it easier for patients to get pain medication during the pandemic, they have not resulted in more diversion or abuse of oxycodone and hydrocodone, according to the Millennium Health Signals Report. Urine positivity rates for the two opioids remained flat during 2020.

“Despite the hardships faced during the pandemic, it is encouraging to see that positivity rates for non-prescribed use of hydrocodone and oxycodone have not changed,” said Michael Parr, MD, an addiction treatment specialist and consultant to Millennium.

“Patients requiring opioids for the treatment of pain have faced difficulty obtaining medications, as well as stigma, before the pandemic. Perhaps this data will reassure clinicians who have taken additional steps to safely prescribe these medications during the pandemic.”

There was an uptick in positivity rates for non-prescribed tramadol, a weaker opioid, particularly in Ohio, Tennessee and Kentucky. Millennium said there were more cases of people with substance use disorders using tramadol as their “drug of preference.”

Millennium researchers also found that positivity rates for non-prescribed gabapentin (Neurontin) showed little change in 2020 – but they remain at levels nearly three times higher than positivity rates for oxycodone, hydrocodone and tramadol. The abuse of non-prescribed gabapentin did rise significantly in Ohio and Virginia.

POSITIVITY RATES FOR NON-PRESCRIBED PAIN MEDICATIONS

SOURCE: MILLENNIUM HEALTH

SOURCE: MILLENNIUM HEALTH

The abuse of gabapentin has been going on for years, but with little public attention. Gabapentin is a non-opioid nerve medication increasingly prescribed for pain, despite the fact many patients say it doesn’t help and has too many side effects. Drug abusers, however, have found that gabapentin can heighten the effect of heroin and other street drugs.

While positivity rates for non-prescribed pain medication were mostly unchanged during the pandemic, they soared for illicit fentanyl and methamphetamine, increasing 78% and 29%, respectively.

After initially increasing in the early stages of the COVID-19 crisis, Millennium found that positivity rates for cocaine and heroin soon returned to pre-pandemic levels.

Another encouraging sign is that positivity rates for carfentanil, a deadly fentanyl analogue, have flatlined to nearly zero. It is unclear why carfentanil abuse has fallen so sharply, but Millennium said it may be because the pandemic has disrupted manufacturing and supply routes from China.     

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.

Tramadol Raises Risk of Low Blood Sugar

By Pat Anson, PNN Editor

Patients who take the opioid tramadol are at greater risk for developing hypoglycemia – a condition caused by very low blood sugar -- than those taking other pain medications, according to researchers at the University of California San Diego.

Prescriptions for tramadol – a synthetic opioid sold under the brand names Ultram and ConZip – have been increasing because it is perceived as a “safer” opioid with less rick of addiction. Tramadol is currently ranked among the top five prescribed opioids in the United States.

As tramadol use has grown, so have documented cases of adverse effects such as dizziness, nausea, headaches and constipation — all common side effects of opioids.

The link to hypoglycemia was discovered by accident when researchers at UCSD’s Skaggs School of Pharmacy and Pharmaceutical Sciences analyzed more than 12 million reports from the FDA’s Adverse Event Reporting System from January 2004 to March 2019.

“The impetus was the recent dramatic surge in tramadol popularity and prescriptions,” said Tigran Makunts, PharmD, first author of the study published in Scientific Reports. “We wanted to have an objective data-driven look at its adverse effects and bumped into a dangerous, unlisted and unexpected hypoglycemia.”

The researchers compared adverse events involving tramadol to those linked to other widely prescribed opioids and non-opioid medications, such serotonin and norepinephrine reuptake inhibitors (Cymbalta, Effexor XR) and NMDA receptors (ketamine and memantine).

Only tramadol produced a significant risk of developing hypoglycemia. There was a 10-fold greater risk of hypoglycemia using tramadol than virtually every other opioid except methadone, which is typically used to treat addiction.

Hypoglycemia is often related to the treatment of diabetes, but can also occur in persons without diabetes. Left untreated, hypoglycemia can lead to serious complications, such as neurocognitive dysfunction, vision loss, greater risk of falls and loss of quality of life.

“The takeaway message is to warn physicians about the likelihood of low blood sugar, in particular if the patient is predisposed to diabetes,” said senior author Ruben Abagyan, PhD, a professor of pharmacy at UCSD.

“It may be beneficial to monitor glucose levels when initiating tramadol or methadone in both diabetic and non-diabetic patients. Alternative opioids or non-opioid pain medications may be safer to use with patients at risk of hypoglycemia or any complications associated with hypoglycemia.”

Tramadol was classified in 2014 by the DEA as a Schedule IV controlled substance, a category that means it has a low potential for abuse. A recent study, however, by Mayo Clinic researchers found that patients who took tramadol for post-surgical pain have a slightly higher risk of prolonged use than those taking oxycodone or other short acting 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.

Study Finds Antidepressants Make Tramadol Less Effective for Pain Relief

By Pat Anson, PNN Editor

Common antidepressants interact with the opioid medication tramadol to make it less effective for pain relief, according to a small new study from University Hospitals (UH) in Cleveland. The findings suggest that some patients who exceed their prescribed dose of tramadol may be under-medicated and are seeking more effective pain relief.

Prescriptions for tramadol – which is sold under the brand names Ultram and ConZip – have increased in recent years because it is widely perceived as a “safer” opioid with less rick of addiction. Many patients, however, say tramadol is not as effective as hydrocodone, oxycodone and other opioids.  

UH researchers reviewed the prescription records of 152 patients who received tramadol for at least 24 hours.

Those patients who were also taking the antidepressants Prozac (fluoxetine), Paxil (paroxetine) or Wellbutrin (bupropion) required three times more tramadol per day to control their breakthrough pain, compared to patients not taking the antidepressants.

Previous studies on healthy volunteers have shown effects on blood levels when combining tramadol with those particular antidepressants. However, this was the first study to document the effects of this interaction in a real-world setting with pain patients.

"We knew that there was a theoretical problem, but we didn't know what it meant as far as what's happening to pain control for patients," said Derek Frost, PharmD, a UH pharmacist and lead author of the study, which was published in the journal Pharmacotherapy.

Frost says millions of Americans may be suffering the ill effects of this drug-to-drug interaction.

"Tramadol relies on activation of the CYP2D6 enzyme to give you that pain control," Frost said. "This enzyme can be inhibited by medications that are strong CYP2D6 inhibitors, such as fluoxetine, paroxetine and bupropion.

“Many chronic pain patients are taking antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), which many of these CYP2D6 inhibitors fit into. There are a lot of patients who experience both, unfortunately. The likelihood that somebody on one of these offending agents and tramadol is relatively high."

Frost says the problem has a relatively easy fix.

"We have a lot of other antidepressants available that are in the same class of medication that don't inhibit this particular enzyme, such as Zoloft (sertraline), (Celexa) citalopram and Lexapro (escitalopram)," he said. "You also have other options for pain control - non-opioid medications such as NSAIDs. If we need to use opioids, a scheduled morphine or a scheduled oxycodone would avoid this interaction."

Tramadol is a synthetic opioid that was rescheduled by the Drug Enforcement Administration in 2014 as a Schedule IV controlled substance, a category that means it has a low potential for abuse. That same year, hydrocodone was rescheduled as a Schedule II drug, meaning it has a high potential for abuse. Many patients who were taking hydrocodone were switched to tramadol as a result of the rescheduling.

Is Tramadol Just as Addictive as Other Opioids?

By Pat Anson, PNN Editor

Patients recovering from surgery who take the opioid tramadol have a slightly higher risk of prolonged use than those receiving oxycodone or other short acting opioids, according to a large Mayo Clinic study.

Prescriptions for tramadol – which is sold under the brand names Ultram and ConZip – have been increasing because it is widely perceived as a “safer” opioid with less rick of addiction. The new study, published in The BMJ, appears to debunk that claim, at least for surgery patients.

Mayo Clinic researchers looked at health data for over 350,000 patients who were prescribed opioids after undergoing 20 common surgeries in the U.S. between 2009 and 2018. A little over 7% of the patients were still refilling opioid prescriptions 90-180 days later. When the researchers dug a little deeper into the data, they found that patients taking tramadol had a 6 percent higher risk of prolonged use compared to other 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. "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."

Tramadol is a synthetic opioid that was classified as a Schedule IV controlled substance by the Drug Enforcement Administration in 2014, a category that means it has a low potential for abuse. That same year, hydrocodone was rescheduled as a Schedule II drug, meaning it has a high potential for abuse.

Many patients who were taking hydrocodone were switched to tramadol as a result of the rescheduling.

Over half (53%) of the patients in the Mayo Clinic study were prescribed hydrocodone, about a third (37.5%) received oxycodone (also a Schedule II drug) , and only 4% received tramadol.

"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," said senior author Molly Jeffery, PhD, the scientific director of research for the Mayo Clinic Division of Emergency Medicine. "This doesn't tie to the idea that tramadol is less habit forming than other opioids."

Jeffery and his colleagues say the DEA and FDA should consider reclassifying tramadol to a level that better reflects the risk of prolonged use.

"Given that tramadol is not as tightly regulated as other short-acting opioids, these findings warrant attention," said Thiels.

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.

Tramadol was classified as a Schedule 3 drug in the United Kingdom in 2014. It is an unscheduled drug in Canada, but Health Canada is currently reviewing its status.

FDA Bans Use of Codeine and Tramadol in Children

By Pat Anson, Editor

The U.S. Food and Drug Administration is tightening restrictions on the use of codeine and tramadol in young children.

The agency says the opioid medications carry "serious risks" for children under the age of 12, including slowed or difficult breathing and possibly even death. The FDA is also recommending against the use of codeine and tramadol by breastfeeding mothers due to possible harm to their infants.

Codeine is approved to treat mild pain and cough, while tramadol is used to treat moderate pain. Codeine is usually combined with other medicines, such as acetaminophen, in prescription pain medication, as well as in some over-the-counter (OTC) cough and cold remedies. The FDA action only applies to prescription codeine.

"We know that some children who received codeine or tramadol have experienced life-threatening respiratory depression and death because they metabolize these medicines much faster than usual, casing dangerously high levels of active drug in their bodies," said Doug Throckmorton, MD, deputy director for regulatory programs, at the FDA Center for Drug Evaluation and Research.

"This is especially concerning in children under 12 years of age and adolescents who are obese or have conditions that may increase the risk of breathing problems, like obstructive sleep apnea or lung disease. Respiratory depression can also occur in nursing babies, when mothers who are ultra-rapid metabolizers take these types of medicines and pass it along to their children through their breast milk."

In a review of adverse event reports from 1969 to 2015, the FDA said it identified 64 cases of serious breathing problems, including 24 deaths, with codeine-containing medicines in children younger than 18. The agency also identified nine cases of serious breathing problems, including three deaths, with the use of tramadol by children.

The majority of serious side effects with both codeine and tramadol occurred in children younger than 12, and some cases occurred after a single dose.

The FDA is requiring drug makers to add a tougher warning to the labels of codeine and tramadol products, alerting healthcare providers and parents that codeine should not be used to treat pain or cough and tramadol should not be used to treat pain in children younger than 12.

The new labeling also cautions against their use in adolescents between 12 and 18 who are obese or have conditions such as obstructive sleep apnea or severe lung disease. Breastfeeding mothers will also be warned not to use the medications.

The FDA said it is considering additional regulatory action for the OTC codeine products that are available in some states. It is also considering an FDA Advisory Committee meeting to discuss the role of prescription opioid cough-and-cold medicines, including codeine, to treat cough in children.

The agency did not recommend or suggest any alternatives to codeine and tramadol to treat childrens' cough or pain. OTC medicines such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) also have risks and side effects.

"We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe," said Throckmorton.

In 2015, the FDA approved the use of OxyContin in children ages 11 to 16  who are in severe pain, a move widely panned by addiction treatment activists who claimed kids would get easily hooked on the painkiller. 

Tramadol ER Visits Soar as Prescriptions Rise

By Pat Anson, Editor

Emergency room visits in the U.S. involving tramadol have nearly tripled in the last decade, coinciding with a sharp increase in the number of prescriptions for the opioid pain reliever.

According to a report by the Substance Abuse and Mental Health Services Administration (SAMHSA), emergency room visits involving adverse reactions to tramadol rose from 10,901 visits in 2005 to 27,421 visits in 2011. A second SAMHSA report  found a similar increase in the number of ER visits related to the abuse or misuse of tramadol. The vast majority of patients were treated and released.

Ironically, tramadol is considered less risky than other opioid painkillers and doctors have been increasingly prescribing it. The IMS Institute recently reported the number of tramadol prescriptions in the U.S. nearly doubled from 28 million in 2010 to over 44.2 million in 2014.

Tramadol is the active ingredient in brand name pain relievers such as Ultram, Ultracet, Ryzolt and Rybix.

“Tramadol is not abused as much as most pain medication, but it is often overtaken in an effort to obtain additional pain relief.  Like with all pain medication, excessive amounts can cause serious harm,” said Lynn Webster, MD, past president of the American Academy of Pain Medicine and vice president of scientific affairs at PRA Health Sciences.

50mgtramadolhclakyma.jpg

Webster predicted that tramadol would be prescribed even more often when hydrocodone was reclassified in 2014 by the Drug Enforcement Administration from a Schedule III drug to a more restrictive Schedule II medication. Tramadol is a Schedule IV drug, meaning it has less potential for abuse than other narcotic pain relievers.

“In the past several years there has been tremendous pressure to reduce prescribing strong opioids. Tramadol has been used in place of other opioids. But it is not without risks as well,” said Webster in an email to Pain News Network.

“The rise in problems associated with tramadol underscores the larger problem of an unmet need to effectively treat pain. Most people, including policymakers, don't realize how many people are desperate to have their pain treated.”

About two-thirds of the ER visits related to misuse or abuse involved tramadol that was taken with other opioid pain relievers or anti-anxiety drugs (benzodiazepines). When tramadol is combined with other drugs that depress the central nervous system its sedative effects can be enhanced, causing seizures and a potentially fatal drug reaction known as serotonin syndrome.

Women were far more likely to have a tramadol-related trip to the ER than men, according to SAMHSA.

The greatest increase in tramadol-related misuse or abuse occurred in patients aged 55 and older. A SAMHSA spokesman said the higher number of older adults was not surprising because seniors are more likely to combine tramadol with other medication.

"Tramadol and other pain relievers can help to alleviate pain, but they must be used carefully and in close consultation with a physician," said SAMHSA Chief Medical Officer Elinore McCance-Katz, MD. "Like all medications tramadol can cause adverse reactions, which can be even more severe if the drug is misused. We must all work to lower the risks of taking prescription drugs.”