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.