Do codeine and caffeine enhance the analgesic effect of aspirin?-A systematic overview

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Abstract
Objective: To assess whether codeine and caffeine enhance the analgesic effect of aspirin in postoperative pain. Method: Systematic overview of the literature and meta‐analysis of published randomized controlled trials (RCTs). Results: Codeine 60 mg leads to a small increase in the analgesic effect of 650 mg of aspirin when total pain relief score (TOTPAE.%) is used as an efficacy end‐point. This increased effect was not seen when sum of pain intensity (SPID%) and proportion of patients responding with moderate to excellent pain relief were used as outcome measures. Caffeine did not enhance the analgesic effect of aspirin. Conclusion: Codeine 60 mg may produce a small increase in the analgesic effect of aspirin 650 mg. However, this effect is not clinically meaningful. Caffeine has no adjuvant analgesic effect. At over‐the‐counter (OTC) doses, caffeine and codeine are not useful in aspirin formulations.