Is the combination of ibuprofen and caffeine effective for the treatment of a tension-type headache?

BACKGROUND: Studies have shown the effectiveness of the addition of caffeine to ibuprofen for acute pain. However, this combination for use in tension-type headaches has been less well studied because of insensitive methods for evaluating this type of headache pain. The purpose of this study was to evaluate the efficacy of ibuprofen plus caffeine for the treatment of tension-type headaches and to establish a sensitive method to compare the combination versus either agent alone.

POPULATION STUDIED: This multicenter study reported on 301 evaluable patients with a history of tension-type headaches as defined by the International Headache Society.¹ The mean age of the patients was 37 years. Patients were included who had 3 to 15 tension-type headaches every month for the past year and were responsive to over-the-counter analgesics at least 75% of the time. Patients who also suffered from migraines were able to participate if the type of headache pain could be differentiated by the quality of the pain or associated symptoms. Patients were excluded if they were allergic to the study drugs or had a comorbid illness that could potentially affect the pharmacokinetics of the study medication.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind parallel single-dose placebo-controlled trial comparing ibuprofen (400 mg) plus caffeine (200 mg), ibuprofen (400 mg), caffeine (200 mg), or placebo. Patients were instructed to take the study medication to treat a tension-type headache of at least moderate severity. They rated baseline pain intensity (4-point scale) and pain intensity and pain relief (5-point scale) at several time points over the next 6 hours. Patients were also given 2 stopwatches and were instructed to start both of them when the dose of medication was taken, to stop one at the onset of perceptible headache improvement, and to stop the second one after achieving meaningful headache improvement.

OUTCOMES MEASURED: Pain reduction, pain relief, and onset of relief measured as time to first perceptible relief and time to meaningful relief were the primary outcomes.

RESULTS: Pain reduction and pain relief were significantly greater for the combination of ibuprofen plus caffeine compared with placebo or either agent alone. The median time to perceptible and meaningful headache improvement was faster for patients treated with ibuprofen plus caffeine compared with ibuprofen alone or placebo (P <.05), though it was not different from caffeine alone. However, 80% of patients receiving ibuprofen plus caffeine experienced a meaningful improvement in headache compared with 67%, 61%, and 56% receiving ibuprofen alone, caffeine alone, or placebo, respectively. The percentage of patients achieving complete relief did not differ between the groups, perhaps because of the small sample size. Overall evaluations of the study medication were higher for the combination than for either agent alone or placebo (P=.007). The most common adverse effects reported were nervousness, nausea, and dizziness and occurred primarily in patients receiving either caffeine alone or ibuprofen plus caffeine.