A comprehensive new analysis published in BMJ Evidence-Based Medicine challenges the widespread use of tramadol for chronic pain management, revealing that the opioid provides minimal therapeutic benefit while significantly increasing the risk of serious cardiovascular complications. The Danish-led study examined 19 clinical trials involving 6,506 patients and found that tramadol's pain-relieving effects fall below clinically meaningful thresholds.
Limited Pain Relief Despite Widespread Use
The research comes at a critical time when 51.6 million American adults—roughly one in five—live with chronic pain, according to the Centers for Disease Control and Prevention. For 17.1 million of them, the condition severely disrupts work and daily activities. Despite this massive patient population, doctors wrote 16 million prescriptions for tramadol in 2023 alone, making it one of the most commonly prescribed pain medications.
Dr. Janus Jakobsen, lead author and clinical professor at the University of Southern Denmark in Copenhagen, explained the study's significance: "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."
The pooled analysis examined trials published between 1998 and 2024, focusing on patients with various chronic pain conditions including fibromyalgia, osteoarthritis, diabetic nerve pain, and chronic low back pain. Participants averaged 58 years of age and received treatment for periods ranging from two to 16 weeks.
Cardiovascular Risks Outweigh Benefits
The study's most alarming finding was tramadol's association with serious adverse events. Statistical analysis showed users had twice the odds of suffering drug-related harms compared to those receiving placebo during follow-up periods of seven to 16 weeks. This increased risk was primarily driven by cardiac events, including chest pain, coronary artery disease, and congestive heart failure.
"The potential harms associated with tramadol use for pain management likely outweigh its limited benefits," the research team concluded. The drug also appeared to raise the risk of milder side effects such as nausea, dizziness, constipation, and sleepiness.
Dr. Michael Hooten, an anesthesiologist and pain specialist at Mayo Clinic who was not involved in the study, provided clinical context: "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."
Challenging the "Safer Opioid" Narrative
Tramadol has long been marketed as a safer alternative to stronger opioids, with less stringent regulatory oversight and a reputation for causing fewer side effects and carrying lower addiction risk. However, the new analysis suggests this perception may be unfounded.
"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," Jakobsen noted. The study found that nearly 12 million daily doses of tramadol were consumed worldwide from 1990 to 2009, according to manufacturer records.
Dr. Jason Chang, assistant professor and interventional spine expert at Columbia University's Vagelos College of Physicians and Surgeons, emphasized the need for more targeted use: "Tramadol is not a magic bullet—on average, it provides only modest pain relief, and it carries real risks. 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."
Implications for Clinical Practice
The research team acknowledged a high risk of bias in the study outcomes but suggested that positive effects of tramadol were likely overstated while negative effects were probably downplayed. All included trials except two were assessed as having high risk of bias, potentially presenting an overly favorable view of tramadol's efficacy.
Dr. Erika Schwartz, a New York-based internist, provided a stark clinical perspective: "I do not prescribe tramadol for chronic pain. Period. The risks are clear from this study. 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."
Broader Context of the Opioid Crisis
These findings emerge against the backdrop of America's ongoing opioid epidemic, which has claimed hundreds of thousands of lives since the late 1990s. The study authors noted that opioid-related overdose deaths increased from 49,860 in 2019 to 81,806 in 2022, with studies showing that up to 12% of people treated with opioids for chronic pain develop addiction or misuse patterns.
"Given these trends and the present findings, the use of tramadol and other opioids should be minimized to the greatest extent possible," the researchers concluded.
The study's limitations include varying follow-up periods across trials and grouping of diverse pain conditions, which may obscure differences in tramadol's effectiveness for specific diagnoses. Additionally, the research only compared tramadol to placebo rather than other active treatments, leaving questions about its relative effectiveness compared to alternatives like NSAIDs or neuropathic medications.
As the medical community grapples with these findings, the research underscores the urgent need for evidence-based approaches to chronic pain management that prioritize patient safety while addressing the complex needs of millions suffering from persistent pain conditions.
