Tramadol Treatment Risks Outweigh Pain Relief Effect According to Results of a Meta-Analysis

Treatment with tramadol, an opioid pain medication and serotonin-norepinephrine reuptake inhibitor (SNRI), was found to provide only slight pain relief with a low certainty of evidence in adults with chronic pain, while substantially increasing risk of serious and nonserious adverse events (AEs). In an article published in BMJ Evidence-Based Medicine, the study authors conclude that the limited benefits of tramadol are likely outweighed by its potential harms as a treatment for people with chronic pain. 

In this systematic review, researchers analyzed 19 randomized placebo-controlled trials, which included a total of 6506 participants with various chronic pain conditions including osteoarthritis, neuropathic pain, fibromyalgia, and chronic low back pain. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane risk-of-bias guidelines, using trial sequential and Grading Recommendations Assessment Development Evaluation (GRADE) analyses to assess both efficacy and safety outcomes.

Key findings from the study include the following:

• Tramadol treatment was associated with a reduction in chronic pain (numerical rating scale mean difference, -0.93 points; 97.5% CI -1.26 to -0.60; P<.0001), but the effect size was below the minimal clinically important difference of 1.0.
• Tramadol treatment was associated with serious AEs primarily due to increased cardiac events and new neoplasms (odds ratio [OR], 2.12; 95% CI, 1.29 to 3.51; P=.001).
• Common nonserious adverse events included:
• Nausea
• Dizziness
• Constipation
• Somnolence
• Fatigue
• Dry mouth
• Insomnia

Researchers rated the evidence for pain reduction as low certainty, while the risk of serious AEs carried moderate certainty. Overall, the authors recommended reconsidering tramadol’s role in chronic pain management in favor of safer, evidence-based alternatives.

Source: Barakji JA, Maagaard M, Petersen JJ, et al. Tramadol versus placebo for chronic pain: a systematic review with meta-analysis and trial sequential analysis. BMJ Evidence-Based Medicine. 2025;0(0):1-10. doi: 10.1136/bmjebm-2025-114101.