Comparison 1. Tramadol versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain	10		Std. Mean Difference (Fixed, 95% CI)	‐0.25 [‐0.32, ‐0.19]
1.1 Tramadol alone	8		Std. Mean Difference (Fixed, 95% CI)	‐0.25 [‐0.32, ‐0.18]
1.2 Tramadol in combination with acetaminophen	2		Std. Mean Difference (Fixed, 95% CI)	‐0.28 [‐0.45, ‐0.12]
2 Physical function	7		Std. Mean Difference (Fixed, 95% CI)	‐0.22 [‐0.30, ‐0.14]
2.1 Tramadol alone	5		Std. Mean Difference (Fixed, 95% CI)	‐0.20 [‐0.29, ‐0.12]
2.2 Tramadol in combination with acetaminophen	2		Std. Mean Difference (Fixed, 95% CI)	‐0.27 [‐0.43, ‐0.11]
3 Number of participants experiencing any adverse events	5	2347	Risk Ratio (IV, Fixed, 95% CI)	1.36 [1.26, 1.48]
3.1 Tramadol alone	4	2039	Risk Ratio (IV, Fixed, 95% CI)	1.34 [1.24, 1.46]
3.2 Tramadol in combination with acetaminophen	1	308	Risk Ratio (IV, Fixed, 95% CI)	1.91 [1.32, 2.76]
4 Number of participants who withdrew due to adverse events	11	5147	Risk Ratio (IV, Fixed, 95% CI)	2.65 [2.20, 3.19]
4.1 Tramadol alone	9	4533	Risk Ratio (IV, Fixed, 95% CI)	2.64 [2.17, 3.20]
4.2 Tramadol in combination with acetaminophen	2	614	Risk Ratio (IV, Fixed, 95% CI)	2.78 [1.50, 5.16]
5 Number of participants experiencing any serious adverse events	8	3627	Risk Ratio (IV, Fixed, 95% CI)	1.78 [1.11, 2.84]
5.1 Tramadol alone	7	3612	Risk Ratio (IV, Fixed, 95% CI)	1.78 [1.11, 2.84]
5.2 Tramadol in combination with acetaminophen	1	15	Risk Ratio (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]