Clinical Question

Does adding caffeine to analgesic medications provide additional pain relief?

Evidence-Based Answer

Overall, there appears to be a small but clinically significant benefit to adding caffeine to analgesic therapy for various types of acute pain. More research is needed to determine the optimal dosing. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Caffeine is used throughout the world for its psychoactive stimulant properties. Although caffeine was likely first added to analgesics to offset their sedating properties, it has more recently been thought to have a synergistic effect on pain relief when used with analgesics.¹

This Cochrane review included 19 randomized, controlled, double-blind studies with a total of 7,238 participants, and examined the effectiveness of caffeine as an adjuvant drug for the treatment of pain. The review addressed oral caffeine in the setting of different types of acute pain, with different types of medications, and at various doses.

Most of the studies examined the effectiveness of adding caffeine to analgesic medications for postpartum pain after episiotomy, postoperative dental pain, headache, and dysmenorrhea. For all conditions, the outcome of interest was the number of participants achieving at least 50 percent of the maximum possible pain relief during the study. In the four studies that involved postpartum pain, the number needed to treat (NNT) for one additional patient to have pain relief by adding caffeine was 16. Among the five studies that evaluated postoperative dental pain, the NNT was 13. In the four studies that involved headache pain, the NNT was 14. Finally, in a single study of dysmenorrhea pain, investigators saw an absolute difference of 4 percent with an NNT of 25 in favor of adjuvant caffeine therapy.

All of the studies examined the effectiveness of caffeine when added to acetaminophen or various nonsteroidal anti-inflammatory drugs, regardless of the patient's type of pain. Eight studies that evaluated acetaminophen therapy with and without caffeine showed an NNT of 15 in favor of combining acetaminophen with caffeine. Four studies compared ibuprofen therapy with and without caffeine, resulting in an NNT of nine in favor of adding caffeine. One study that involved 91 patients showed an absolute difference of 14 percent and an NNT of seven in favor of using caffeine with diclofenac (Voltaren). Studies examining the use of caffeine with aspirin and tolfenamic acid (not available in the United States) showed no significant differences.

Studies were grouped according to doses of caffeine used: 65 mg or less, 70 to 150 mg, and more than 150 mg. Five studies, all examining postoperative pain, used 65 mg or less of caffeine and found no significant differences between treatment groups. (Most over-the-counter analgesics with caffeine that are sold in the United States contain 65 mg of caffeine or less.²) In the 12 studies that used 70- to 150-mg doses of caffeine, the NNT for adding caffeine to benefit one additional person was 14. Lastly, in the six studies that used a caffeine dose of more than 150 mg, the NNT was 10. However, because lower doses of caffeine were typically given with lower doses of analgesics, it is unclear whether higher doses of caffeine would be more effective.