Effect of caffeine on acetaminophen analgesia

Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping, episiotomy, and third molar extraction. In the dental study, 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine. In the three postpartum studies, 1345 patients received one, two, or three tablets of acetaminophen, the combination, or a placebo. The mean scores for the summary variable percent sum of the pain intensity differences (% SPID) were higher in all for the combination than for acetaminophen alone, and in two studies the null hypothesis of no differences was rejected. The relative potency estimates for % SPID were 1.9, 1.8, and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95% confidence interval of 1.1 to 3.1. The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption. Onset of analgesia was also faster with the combination. We conclude that caffeine enhances the analgesic efficacy of acetaminophen.