A widely prescribed pain reliever drug for chronic pain may have limited benefits and serious health risks, researchers warn. Tramadol, a powerful opioid, may increase the risk of serious side effects, including heart disease, and the dangers associated with its use may outweigh the benefits, according to a large review.
A drug widely used to treat pain may be more dangerous than previously thought. Tramadol, a powerful opioid pain reliever commonly prescribed for chronic pain, provides only modest pain relief, and the risks associated with its use likely outweigh the benefits, according to a large review of existing studies. The findings come from a combined review of available research, published online in the journal BMJ Evidence-Based Medicine and cited by SciTechDaily.
Researchers warn that tramadol treatment is associated with a higher likelihood of serious side effects, including cardiovascular disease. Based on these results, they recommend reducing the use of this drug.
An opioid perceived as ‘safer’
Tramadol is a dual-acting opioid used to manage moderate to severe pain, both acute and chronic. For this reason, it appears in several clinical guidelines as a treatment option for pain, the study authors explain.
In recent years, the prescription of tramadol has increased significantly, especially in the United States, where it has become one of the most widely used opioids. This increase may reflect the widespread perception that tramadol has fewer side effects and less potential for addiction compared to other short-acting analgesics.
Although the drug has been looked at in other systematic reviews, the researchers point out that until now there has been no comprehensive evaluation that considers both its effectiveness and safety for a wide range of chronic pain conditions.
What the study analysis shows
To fill this information gap, the research team searched medical databases for randomized clinical trials published up to February 2025 that compared tramadol with placebo among patients with chronic pain, including cancer-related pain.
In total, 19 clinical trials with 6,506 participants were included. Five studies looked at neuropathic pain, nine focused on osteoarthritis, four looked at chronic low back pain, and one looked at .
The average age of the participants was 58 years, with values ranging from 47 to 69 years. Most studies used tramadol in tablet form; only one study included a topical cream. The duration of treatment varied between two and 16 weeks, and the follow-up period between three and 15 weeks.
The combined analysis of the results showed that although tramadol reduces pain, the effect is small and below the threshold considered clinically relevant.
Double risk of serious adverse effects
Eight of the studies reviewed reported the occurrence of serious adverse effects with follow-up periods of between seven and 16 weeks. Statistical analysis indicates a doubling of the risk of such effects in patients treated with tramadol compared to placebo.
The increase in risk was mainly driven by a greater number of “cardiac events”such as chest pain, coronary heart disease and congestive heart failure.
Tramadol use has also been associated with an increased risk of certain types of cancer, but the follow-up period was short, making this result “questionable”, according to the researchers.
Analysis of all studies also showed an increased risk of milder side effects such as nausea, dizziness, constipation and drowsiness.
The authors acknowledge that the results are at high risk of methodological errors, but point out that this makes it more likely that the benefits of tramadol are overestimated and the harmful effects are underestimated.
The broader context of the opioid crisis
The researchers place these findings in an alarming global context. “Aapproximately 60 million people worldwide experience the addictive effects of opioids. In 2019, drug use was responsible for approximately 600,000 deaths, nearly 80% of which were associated with opioids, and approximately 25% were caused by opioid overdoses“, show the authors.
They add: “In the United States, the no deaths caused by opioid overdoses increased from 49,860 in 2019 to 81,806 in 2022. Given these trends and the results of the present study, the use of tramadol and other opioids should be reduced as much as possible.”
The researchers’ conclusion is clear: “Tramadol may have a mild effect in reducing chronic pain (low certainty of evidence), but is likely to increase the risk of both serious adverse events (moderate certainty of evidence) and non-serious adverse events (very low certainty of evidence). Potential harmful effects associated with tramadol use for pain management most likely outweigh its limited benefits.”
The cited study is titled “Tramadol versus placebo in chronic pain: a systematic review with meta-analysis and sequential analysis of studies” and was published on October 7, 2025 in BMJ Evidence-Based Medicine.
