The quality of evidence is downgraded by study limitations (lack of allocation concealment)
A Cochrane review [Abstract] 1 included 22 studies with a total of 3871 participants randomized to tramadol alone or tramadol in combination with another analgesic and 2625 participants randomized to placebo or active control. Seventeen studies evaluated tramadol alone and five evaluated tramadol plus acetaminophen. Thirteen studies used placebo controls and eleven studies used active controls (two trials had both placebo and active arms). The dose of tramadol ranged from 37.5 mg to 400 mg daily. Most trials were multicenter with a mean duration of two months. Participants were predominantly women with hip or knee osteoarthritis, with a mean age of 63 years and moderate to severe pain.
Tramadol alone and in combination with acetaminophen had no important benefit on pain reduction compared to placebo control (tramadol alone: 4% absolute improvement, 95% CI 3% to 5%; 8 studies, 3972 participants; tramadol in combination with acetaminophen: 4% absolute improvement, 95% CI 2% to 6%; 2 studies, 614 participants).Fifteen out of 100 people in the tramadol group improved by 20% (which corresponded to a clinically important difference in pain) compared to 10/100 in the placebo group (5% absolute improvement). Twelve out of 100 people improved by 20% in the tramadol in combination with acetaminophen group compared to 7/100 in the placebo group (5% absolute improvement).
Tramadol alone and in combination with acetaminophen led to no important benefit in physical function compared to placebo (tramadol alone: 4% absolute improvement, 95% CI 2% to 6%; 5 studies, 2550 participants; tramadol in combination with acetaminophen: 4% absolute improvement, 95% CI 2% to 7%; 2 studies, 614 participants).Twenty‐one out of 100 people in the tramadol group improved by 20% (which corresponded to a clinically important difference in physical function) compared to 16/100 in the placebo group (5% absolute improvement). Fifteen out of 100 people improved by 20% in the tramadol in combination with acetaminophen group compared to 10/100 in the placebo group (5% absolute improvement).
Compared to placebo, there was a greater risk of developing adverse events with tramadol alone (RR 1.34, 95% CI 1.24 to 1.46; 4 studies, 2039 participants) and tramadol in combination with acetaminophen compared to placebo (RR 1.91, 95% CI 1.32 to 2.76; 1 study, 308 participants). This corresponded to a 17% increase (95% CI 12% to 23%) with tramadol alone and 22% increase (95% CI 8% to 41%) with tramadol in combination with acetaminophen.The three most frequent adverse events were nausea, dizziness and tiredness.
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