A recent evidence-based analysis published in BMJ Evidence-Based Medicine has raised concerns about the safety profile of tramadol, a widely prescribed opioid analgesic, particularly in comparison with its modest pain-relief benefits. The findings add to a growing body of literature questioning tramadol’s long-standing reputation as a “safer” opioid alternative.
Tramadol is commonly used for moderate to moderately severe pain, especially in postoperative, musculoskeletal, and chronic pain settings. Unlike traditional opioids, tramadol has a dual mechanism of action: it weakly stimulates opioid receptors while also inhibiting the reuptake of serotonin and norepinephrine. This mixed mechanism has often been cited as a reason for its perceived lower abuse potential.
However, researchers note that this same pharmacological complexity may contribute to a broader range of adverse effects, particularly affecting the nervous and cardiovascular systems.
The BMJ Evidence-Based Medicine study reviewed large-scale clinical data comparing tramadol with other commonly used pain medications. The analysis found that tramadol provided minimal additional pain relief for many acute pain conditions while being associated with a higher risk of serious adverse outcomes.
Reported risks included:
Increased incidence of seizures, even at therapeutic doses
Higher rates of hypoglycaemia, particularly in older adults and people with diabetes
Elevated risk of serotonin syndrome, especially when combined with antidepressants
Greater likelihood of cardiovascular events, including arrhythmias
Increased rates of falls, fractures, and hospitalisations
The study also highlighted that tramadol’s metabolism varies significantly between individuals due to genetic differences in liver enzymes, making its effects unpredictable.
One of the notable findings was tramadol’s association with neurological complications. Seizures have been documented even in patients without a prior history of epilepsy. The serotonergic effects of tramadol also raise concerns about interactions with commonly prescribed antidepressants, which may increase the risk of agitation, confusion, and autonomic instability.
Additionally, the study reported a measurable association between tramadol use and episodes of low blood sugar, a complication that can be particularly dangerous in elderly patients.
When compared with non-opioid analgesics and other opioids, tramadol did not demonstrate superior pain control for most short-term pain indications. Despite this, its adverse event profile was found to be comparable or in some cases higher than alternatives.
These findings challenge earlier assumptions that tramadol carries fewer risks than stronger opioids, particularly when prescribed for routine pain management.
The authors of the BMJ analysis emphasised the importance of careful patient selection, dose monitoring, and awareness of drug interactions when prescribing tramadol. They also highlighted the need for clinicians to reassess its role in pain management, especially for populations at higher risk of adverse outcomes.
Tramadol remains widely available in many countries and is often perceived as a relatively benign painkiller. However, emerging evidence suggests that its risk profile warrants closer scrutiny, particularly as healthcare systems seek safer, evidence-based approaches to pain control.
Reference
Jehad Ahmad Barakji et al., “Tramadol versus Placebo for Chronic Pain: A Systematic Review with Meta-Analysis and Trial Sequential Analysis,” BMJ Evidence-Based Medicine, published online September 26, 2025, https://doi.org/10.1136/bmjebm-2025-114101.
(Rh/TL)