Effect of caffeine on acetaminophen analgesia. Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain. Caffeine as an analgesic adjuvant in tension headache. Caffeine as an analgesic adjuvant. A double-blind study comparing aspirin with caffeine to aspirin and placebo in patients with sore throat. Double-blind comparison of an acetaminophen-codeine-caffeine combination in oral surgery pain. A double-blind randomized study of an aspirin/caffeine combination versus acetaminophen/aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain. Aspirin and aspirin-caffeine in postpartum pain relief. The analgesic effects of caffeine in headache. Evaluation of aspirin, caffeine, and their combination in postoperative oral surgery pain.
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. Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin. Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches. In four studies, comprising 1900 patients, the caffeine-containing analgesic consisted of a combination of 500 mg acetaminophen, 500 mg aspirin, and 130 mg caffeine (APAP/ASA/CAF). In two studies, comprising 911 patients, the caffeine-containing analgesic consisted of a combination of 1000 mg acetaminophen and 130 mg caffeine (APAP/CAF). Patients self-medicated for moderate or severe headache pain, and with a self-rating record they rated their pain and its relief hourly for 4 hours. In all six studies, the caffeine-containing analgesics were significantly superior both to placebo and to 1000 mg acetaminophen, and acetaminophen was significantly superior to placebo. The significant analgesic adjuvant effect of caffeine was independent of patients' usual caffeine use or their caffeine consumption in the 4 hours before medication. For each treatment, the pooled analgesic responses for the four studies of APAP/ASA/CAF were virtually superimposable on the responses in the two APAP/CAF studies. The combinations produced more stomach discomfort, nervousness, and dizziness than acetaminophen or placebo. Despite its frequent clinical use in analgesic agents, caffeine has not been accepted unequivocally as an analgesic adjuvant. To evaluate this activity of caffeine, we used new study methods in a randomized controlled trial on patients with acute sore throat due to tonsillopharyngitis. Patients were randomly assigned to receive a single dose of one of three treatments: 800 mg of aspirin with 64 mg of caffeine (n = 70), 800 mg of aspirin (n = 68), or placebo (n = 69). Under double-blind conditions, during a 2-hour evaluation period, patients used different rating scales to assess pain intensity, change in pain, relief, and two qualities of throat pain, how swollen the throat felt, and difficulty swallowing. Aspirin with caffeine and aspirin alone were significantly more effective than placebo for all efficacy measurements from 30 minutes through 2 hours and overall. The aspirin-caffeine combination also showed evidence of activity at 15 minutes on the relief scale. Aspirin with caffeine was more effective than aspirin alone after 30 minutes and over the entire study period. For patients with fever, both active treatments were equally effective antipyretic agents. We conclude, therefore, that 800 mg of aspirin, given alone or with 64 mg of caffeine, is an effective analgesic and antipyretic agent. Because the aspirin-caffeine combination is significantly more effective than aspirin alone as an analgesic, we also conclude that 64 mg of caffeine is an analgesic adjuvant. The purpose of this paper was to evaluate the contribution of low dosages of codeine and caffeine when added to acetaminophen. Subjects were dental outpatients undergoing oral surgery involving bone removal. This was a single-dose, parallel group, double-blind assay evaluting 99 subjects. The treatment groups were acetaminophen 1000 mg, acetaminophen 1000 mg + codeine 16 mg + caffeine 30 mg and placebo. The results demonstrated that both active treatments were superior to placebo. Overall, the combination was slightly better than acetaminophen alone. The advantage of the combination appeared more evident in the "severe" baseline pain group. In a double-blind, randomized controlled trial among 500 post-partum patients experiencing moderate to severe pain, a single oral dose of an aspirin/caffeine combination (800 mg aspirin, 65 mg caffeine) provided significantly more pain relief at 2 hours than did a higher dose of an acetaminophen/aspirin combination (648 mg acetaminophen, 648 mg aspirin) and a higher dose of acetaminophen alone (1000 mg acetaminophen). At 3 and 4 hours, the acetaminophen/aspirin combination as well as the aspirin/caffeine combination were significantly superior to acetaminophen alone. At all times, all three drugs were significantly superior to placebo. There were no clinically significant adverse reactions. These results provide evidence of a potentiating effect of caffeine on aspirin's analgesic potency. In two double-blind randomized, balanced, single oral dose studies with 140 women, a combination of 800 mg aspirin and 64 mg caffeine (aspirin-caffeine) was compared to 650 mg aspirin and to placebo. In patients with moderate to severe uterine or episiotomy pain, there was greater analgesic response with active drugs when the initial pain intensity was more severe. In patients with severe episiotomy pain, aspirin-caffeine was more effective than 650 mg aspirin (p less than 0.05) at the second and third hours. There was no difference between analgesic effects of aspirin and aspirin-caffeine in women with severe uterine pain. Caffeine is frequently added to mild analgesic preparations but its effect when used alone on pain has never been studied in humans. Using a double-blind placebo-controlled multiple crossover design, 53 patients with non-migrainous headaches were given placebo, acetaminophen, 2 doses of caffeine and 2 combinations of caffeine with acetaminophen. Caffeine appeared to have independent analgesic effects that were equivalent to acetaminophen and were still significant when statistical adjustments were made for prior caffeine consumption and caffeine's effects on mood. Three hundred fifty outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments except caffeine were significantly superior to placebo. Pairwise comparisons indicated the aspirin-caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were serious.
The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.