A comprehensive review of clinical trials indicates that tramadol, a widely prescribed opioid for chronic pain, offers only slight relief that may not be noticeable to many patients. However, it significantly increases the risk of serious side effects, particularly heart-related issues. Researchers recommend minimizing its use due to these concerns.
Tramadol has gained popularity as a seemingly safer alternative to other opioids for managing moderate to severe chronic pain, appearing in several clinical guidelines. Prescriptions have surged in the United States, fueled by perceptions of lower addiction risk and fewer side effects compared to short-acting opioids.
To evaluate its true efficacy and safety, researchers conducted a systematic review and meta-analysis of randomized clinical trials published up to February 2025. They analyzed 19 trials involving 6,506 participants, averaging 58 years old, with conditions including neuropathic pain, osteoarthritis, chronic low back pain, and fibromyalgia. Treatments, mostly tablets, lasted 2 to 16 weeks, with follow-ups up to 15 weeks.
The combined results showed tramadol reduces pain modestly, falling short of clinically meaningful improvements. Eight trials monitoring side effects over 7 to 16 weeks revealed roughly double the risk of serious harms versus placebo, driven by cardiac events such as chest pain, coronary artery disease, and congestive heart failure. It also linked to higher incidences of nausea, dizziness, constipation, and sleepiness. A potential cancer risk was noted, though deemed unreliable due to brief follow-up periods.
The study, published in BMJ Evidence-Based Medicine, highlights biases in prior research that may overstate benefits and understate harms. In the broader opioid crisis context, about 60 million people worldwide face addiction, with 600,000 drug-related deaths in 2019—nearly 80% opioid-linked and 25% from overdoses. U.S. opioid overdose deaths rose from 49,860 in 2019 to 81,806 in 2022.
"Tramadol may have a slight effect on reducing chronic pain (low certainty of evidence) while likely increasing the risk of both serious (moderate certainty of evidence) and non-serious adverse events (very low certainty of evidence)," the authors conclude. "The potential harms associated with tramadol use for pain management likely outweigh its limited benefits." They urge reducing opioid prescriptions, including tramadol, as much as possible.
