Forty RCTs containing 75 placebo comparisons and 10 head-to-head comparisons were included.
There were 58 comparisons of ibuprofen versus placebo, involving 4,832 patients.
There were 11 comparisons of ibuprofen and codeine versus placebo, involving 699 patients.
There were 6 comparisons of ibuprofen and caffeine versus placebo, involving 415 patients.
There were 6 comparisons of ibuprofen and codeine versus ibuprofen, involving 414 patients.
There were 4 comparisons of ibuprofen and codeine versus ibuprofen and caffeine, involving 331 patients.
Efficacy of ibuprofen.
Ibuprofen was effective in dental pain, episiotomy pain and other post-operative pain at all the doses administered. Detailed results were presented for the trials of dental pain.
For ibuprofen compared with placebo:
the difference in the percentage total pain-relief score was 27.52 (95% CI: 24.76, 34.32);
the difference in the percentage sum of pain intensity was 21.59 (95% CI: 19.05, 24.12); and
the number-needed-to-treat for one more patient to obtain moderate-to-excellent pain relief was 2.44 (95% CI: 2.19, 2.77).
There was a dose-response relationship over the range 50 to 400 mg.
Additive effects of codeine and caffeine.
When pooling across all types of pain, the difference in percentage total pain-relief score was 8.48 (95% CI: 0.95,16.01) for ibuprofen (400 mg) plus codeine (60 mg), compared with ibuprofen (400 mg) alone.
Indirect comparisons of the addition of codeine were not statistically significant.
The additive effect of caffeine was inconsistent.
Adverse effects.
Patients were more likely to experience drowsiness with both ibuprofen (400 mg) alone and the ibuprofen-codeine combination than with placebo; the relative risks were 2.33 (95% CI: 1.27, 4.27) and 3.74 (95% CI: 1.03, 13.56), respectively.