A Cochrane review included 15 studies with a total of 5540 subjects. Tramadol was examined in five trials with 1378 participants, transdermal buprenorphine in two trials with 653 participants and strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol) in six trials with 1887 participants.
Tramadol was found to be better than placebo for pain (SMD -0.55, 95% CI -0.66 to -0.44) and function (SMD -0.18, 95% CI -0.29 to -0.07). Transdermal buprenorphine may make little difference for pain (SMD -2.47, 95%CI -2.69 to -2.25), but no difference compared to placebo for function (SMD -0.14, 95%CI -0.53 to 0.25). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), were better than placebo for pain (SMD -0.43, 95%CI -0.52 to -0.33) and function (SMD -0.26, 95% CI -0.37 to -0.15).
Tramadol was more effective than placebo for pain relief, SMD 0.71 (95% CI 0.39 to 1.02), and improving function measured by the Roland Disability Questionnaire (RDQ, score 0 to 24, 0 = no disability), SMD 0.17 (95% CI 0.04 to 0.30). An SMD of 0.71 suggests that the use of tramadol, on average, reduced patients' pain scores by approximately 10.8 points on a 100-point VAS. The SMD for the RDQ implies that the use of tramadol improved patients' scores by one point compared with the use of placebo. The two most common side effects of tramadol were headaches, RD 9% (95% CI 6% to 12%) and nausea, RD 3% (95% CI 0% to 6%). In the opioid (oxycodone or morphine sustained release) vs. naproxen study, the results were not statistically significant for either pain relief (SMD -0.58; 95% CI -1.42 to 0.26) or improving function (SMD -0.06; 95% CI -0.88 to 0.76).Comment: The level of evidence is downgraded by study quality (inadequate intention-to-treat adherence and study duration) and limited interpretation of functional improvement.