Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: a meta-analysis

Eur J Clin Pharmacol. 1998 Jan;53(5):303-11. doi: 10.1007/s002280050383.


Objective: To estimate the analgesic effect of ibuprofen and to test whether codeine and caffeine enhance its effect on post-surgical pain.

Method: Systematic overview of the literature and meta-analysis of published randomised, controlled trials.

Results: Ibuprofen is effective in dental pain, episiotomy pain and other post-operative pain. There is a dose response relationship over the range 50-400 mg. The difference in total pain-relief score relative to placebo was 19-31%. On average, patients were over three times more likely to obtain moderate to excellent pain relief with ibuprofen than with placebo (response-rate ratio = 3.45) and the number needed to treat was 2.44. Codeine 60 mg enhanced the analgesic effect of ibuprofen 400 mg by about 8% in the total pain-relief scale, but it also increased its adverse effects. The additive effect of caffeine was inconsistent.

Conclusion: Ibuprofen is an effective analgesic in post-operative pain. Codeine 60 mg adds to the analgesic effect of ibuprofen 400 mg. Any additive caffeine effect requires validation.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Anesthetics, Combined / adverse effects
  • Anesthetics, Combined / therapeutic use*
  • Caffeine / administration & dosage
  • Codeine / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Ibuprofen / administration & dosage
  • Pain, Postoperative / drug therapy*
  • Randomized Controlled Trials as Topic
  • Sleep Stages


  • Anesthetics, Combined
  • Caffeine
  • Codeine
  • Ibuprofen