Common opioid is not that effective for easing chronic pain, study finds

By Jacqueline Howard, CNN

(CNN) — Tramadol, a potent synthetic opioid, has been widely used to treat moderate to severe pain, but a new study suggests that the medication’s potential risks outweigh its “limited” benefits for chronic pain and that the use of it should be minimized.

The study, published Tuesday in the journal BMJ Evidence-Based Medicine, found that tramadol may have a “slight effect” on reducing chronic pain, but there appears to be low evidence.

“The findings indicate that the benefits of tramadol are questionable or, at the very least, uncertain. Furthermore, evidence suggests the presence of potentially harmful effects,” Dr. Janus Jakobsen, lead author of the study and a clinical professor at the University of Southern Denmark in Copenhagen, said in an email.

Tramadol can have serious side effects, including cardiac events such as chest pain, heart disease or congestive heart failure, according to the study.

“Therefore, alternative treatment options should be considered before prescribing tramadol,” Jakobsen said. “Patients are advised to consult their physicians to determine the most appropriate treatment for their condition. Such treatments should likely be individualized according to the type of chronic pain experienced.”

Additionally, opioids as a class of drugs can be addictive. It’s estimated that about 60 million people worldwide experience the addictive effects of opioids, and tramadol is often considered safer than other opioids.

Potential harms versus benefits

According to manufacturer records, the new study says, nearly 12 million daily doses of tramadol were consumed worldwide from 1990 to 2009.

The study, conducted by a research team in Denmark, included an analysis of 19 separate clinical trials that evaluated tramadol versus a placebo in treating various types of chronic pain. The trials were published between 1998 and 2024, and collectively they involved more than 6,500 people ages 47 to 69. Some of the trials included in the study were related to osteoarthritis, diabetic nerve pain and chronic low back pain.

“To our knowledge, this is the first systematic review related to the usage of tramadol for any type of chronic pain with a thorough investigation of adverse events,” the researchers wrote in the study.

Their analysis found that tramadol increased the risk of both non-serious and serious adverse events, including nausea, dizziness, constipation, drowsiness, cardiac problems and “neoplasm” events, which are an abnormal and excessive growth of cells and tissue that can form tumors. These neoplasm growths can be either benign or cancerous.

The researchers also found that there was “low-certainty evidence” that tramadol may reduce the intensity of chronic pain below a certain level that they called the “minimal important difference” threshold.

Typically, pain intensity is measured using a visual or numerical scale, such as when patients are asked to rate their pain on a scale from 0 to 10, with 10 being unbearable pain, Jakobsen said. But since each person may have a difference in pain perception, the researchers used a minimal threshold to evaluate a clinical difference in tramadol’s ability to reduce pain versus a placebo, based on the clinical trials they evaluated.

“Although statistical analyses may reveal differences in pain scores between patients, these differences may be so small that they are not perceptible to the patients themselves,” Jakobsen said. “Therefore, it is crucial to predefine a minimal clinically important difference when assessing pain levels to ensure that the results reflect changes that are meaningful to patients.”

In the new study, the researchers chose a “minimal important difference” that was equivalent to one point on the 10-point numerical rating scale. It appeared that the beneficial effect of tramadol on chronic pain was below that “minimal important difference” of one point, on average.

The Association for Accessible Medicines, which represents manufacturers of generic drugs, didn’t immediately respond to CNN’s request for comment on the new study.

“The takeaway finding that tramadol in randomized placebo-controlled trials did not meet their designated threshold of reducing pain scores by one – I am not too surprised by that,” said Dr. Michael Hooten, an anesthesiologist and pain specialist at Mayo Clinic in Rochester, Minnesota, who was not involved in the new study.

“Opioids for longer-term, persistent chronic pain are not the best medications because of tolerance and other factors that may interfere with the long-term trajectory of opioid therapy,” Hooten said. “As a clinically working pain specialist, this review basically confirms many of the clinical factors that I already intuitively know.”

And although the study found that tramadol may have a “slight effect” on reducing chronic pain levels, that comes with the increased risk of concerning cardiac events and other potential side effects.

“From my perspective, I don’t use a lot of tramadol, because I know there’s going to be a lot of adverse effects. I know the pain-reducing effects are going to be minimal. So that’s not necessarily a drug that I go to,” Hooten said. “That represents my personal, anecdotal clinical practice – if you talk to another pain expert or pain specialist, they’re going to have maybe a completely different opinion. It’s really complex.”

‘Tramadol is not a magic bullet’

The new study could be overestimating tramadol’s benefits, Jakobsen said.

“All included trials, except for two, were assessed as having a high risk of bias. This increases the likelihood that our findings may overestimate the beneficial effects and underestimate the harmful effects of tramadol, potentially presenting an overly favorable view of its efficacy,” Jakobsen said.

“Tramadol remains widely prescribed for the management of chronic pain and is often regarded as safer than other opioids, but without evidence to support this,” he said. “The use of tramadol and other opioids should be minimized as much as possible. Our study provides evidence in support of this recommendation.”

One limitation of the new study is that the amount of time patients were followed varied across the trials, which it makes unclear what the drug’s long-term risks versus benefits may be.

“Most of the included trials were short-term – majority 12 weeks or less – so we can’t draw firm conclusions about long-term safety or sustained benefit,” Dr. Jason Chang, assistant professor and interventional spine and musculoskeletal medicine expert at Columbia University’s Vagelos College of Physicians and Surgeons, said in an email.

“The review also grouped together a wide range of pain conditions, which may obscure differences in how tramadol works for specific diagnoses,” said Chang, who wasn’t involved with the new research. “Finally, the study only compared tramadol to placebo – not to other active treatments – so we don’t know how it stacks up against alternatives like NSAIDs or neuropathic medications.”

NSAIDs are non-steroidal anti-inflammatory drugs, such as ibuprofen and aspirin. Some physicians may prescribe tramadol to people who may not be able to take NSAIDs, for instance due to an underlying health condition or other medications they are taking.

“Tramadol is not a magic bullet – on average, it provides only modest pain relief, and it carries real risks, including nausea, dizziness, constipation, and, in rare cases, more serious complications like cardiac events or seizures,” Chang said.

“It can be useful for select patients who can’t take NSAIDs or need short-term help to restore function, but it should be prescribed with clear functional goals, for limited durations, and with close monitoring for side effects,” he said. “The conversation shouldn’t be about banning tramadol, but about using it smarter – short courses, careful patient selection, and always as part of a plan that prioritizes mobility, function, and quality of life.”

The new research findings were no surprise to Dr. Erika Schwartz, a New York-based internist and author of the book “Don’t Let Your Doctor Kill You.”

“This study confirms what I’ve observed in clinical practice for years – tramadol has been marketed as this ‘safer opioid’ alternative, but the reality is far more complicated,” Schwartz, who was not involved in the research, said in an email.

If someone is prescribed tramadol, Schwartz said, they should ask their provider these questions: Why are they getting this drug? What alternatives exist? Has anyone actually investigated what’s causing their chronic pain in the first place?

It’s estimated that 1 in 5 adults live with chronic pain in the United States, said CNN Chief Medical Correspondent Dr. Sanjay Gupta, author of the book “It Doesn’t Have to Hurt: Your Smart Guide to a Pain-Free Life.”

“About a third of them are restricted in what they can do and how to live. But there are alternatives to medication. We can reduce and even possibly eliminate pain by using our own body’s and mind’s capacity to manage it,” Gupta said. “Options can include meditation and yoga, massage and acupuncture. Even emphasizing eating anti-inflammatory foods like whole grains and leafy greens can help mitigate how our bodies react.”

Nonopioid therapies for pain management may also includer ice or heat, elevation, rest and quality sleep, or physical therapy and exercise. Medications may include NSAIDs, acetaminophen or other non-opioid drugs.

“I do not prescribe tramadol for chronic pain. Period. The risks are clear from this study,” Schwartz said. “The real tragedy is that millions of patients have been prescribed tramadol when what they needed was someone to investigate the actual cause of their pain. We’ve traded real solutions for prescription pads, and patients are suffering for it.”

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