The world’s most commonly prescribed opioid has been shown to offer limited pain relief benefits while elevating the risk of deadly cardiovascular events.
Tramadol, the most popular opioid painkiller around the world, with the US alone seeing over 16 million prescriptions in 2023, has been prescribed for nearly five decades as a treatment for moderate to severe chronic pain. Doctors have relied on it because of a long-held clinical belief that it has a lower potential for addiction compared to other opioids such as oxycodone and fentanyl.
But researchers in Denmark conducted a sweeping analysis of past clinical trials and concluded that not only does the drug offer clinically insignificant pain relief, but it also increases the overall odds of having any serious adverse event by more than double.
The analysis covered 19 studies that included more than 6,500 people taking either tramadol or a placebo drug. The side effects, in addition to higher odds of experiencing chest pain, coronary artery disease (CAD) and congestive heart failure, also included nausea, dizziness and constipation.
The researchers said: ‘Tramadol may have a slight effect on reducing chronic pain (low certainty of evidence) while likely increasing the risk of both serious… and non- serious adverse events.
‘The potential harms associated with tramadol use for pain management likely outweigh its limited benefits.’
Stopping short of suggesting that regulatory bodies around the world consider revoking the drug’s approval, the researchers urged doctors to ‘reconsider’ prescribing it and substitute it for ‘safer alternatives,’ without offering specifics.
Tramadol can be given both in the hospital and outpatient for someone to take at home. Like any opiate, tramadol carries some risk of addiction. Still, it is generally considered to have a lower addiction potential than stronger opioids like oxycodone, earning it a Schedule IV classification by the DEA for its abuse risk.
No precise data track tramadol use in heart patients, but demographics strongly indicate overlap. Tramadol is commonly prescribed for chronic pain in older adults—the very group at highest risk for cardiovascular disease (stock)
Amid the opioid crisis, physicians find it challenging to identify an opioid that is completely safe for pain relief. They are caught between significant pressure to curb prescriptions and the duty to address genuine patient suffering.
Tramadol is very common in the US, ranking as one of the most prescribed opioid painkillers, often the second or third most common, with millions of prescriptions filled annually, driven partly by its perception as safer and less addictive than other opioids.
But the latest research points to the risks associated with the drug far outweighing the benefits.
The average age of participants was 58 years, placing them squarely in the high-risk demographic for developing these cardiac events.
The study population was already at an age where underlying, undiagnosed CAD or cardiac vulnerability is common, and tramadol may have acted as a triggering or exacerbating factor.
Of the 19 pain studies analyzed, five examined nerve pain, nine focused on osteoarthritis, four looked at chronic low back pain and one studied fibromyalgia.
Researchers systematically extracted all data on serious adverse events reported in those 19 pain trials and grouped them into categories, such as cardiac disorders, neoplasms and gastrointestinal disorders.
The ‘cardiac events’ category was created from individual reports like ‘myocardial infarction,’ (heart attack), ‘chest pain’ and ‘congestive heart failure’ that were documented.
A Danish review found tramadol’s pain relief is negligible while more than doubling the risk of serious side effects (stock)
Compared to placebo, patients taking tramadol had 113 percent higher odds, more than double, of experiencing a serious adverse event of any kind.
The study authors then investigated what types of serious adverse events were driving this overall doubling of risk.
Their analysis showed the increase was ‘mainly driven by a higher proportion of cardiac events and neoplasms [tumors],’ but researchers did not say by how much risk was increased for CAD, chest pain or heart attack.
Over 18 million Americans live with CAD, the most common type of heart disease that results when plaque builds up in the heart’s arteries, narrowing them and reducing blood, oxygen and nutrient supply to the heart muscle.
CAD is a leading cause of chest pain, heart attack, heart failure and death.
There are no exact figures tracking tramadol use among cardiac patients, though the demographics of the study suggest significant overlap. Tramadol is often prescribed to older adults with chronic pain, the same population most likely to have cardiovascular disease.
The researchers argued that many heart disease patients are likely exposed to tramadol, making the drug’s cardiac risks especially concerning. Therefore, doctors should look for safer options in practice, such as non-opioid pain relievers, drug-free therapies like specific physical therapies and cognitive behavioral therapy.
The study was published in the BMJ.
