Current issues of ACP Journal Club are published in Annals of Internal Medicine


Aspirin plus caffeine was a more effective analgesic for sore throat than aspirin alone

ACP J Club. 1991 Sept-Oct;115:52. doi:10.7326/ACPJC-1991-115-2-052

Source Citation

Schachtel BP, Fillingim JM, Lane AC, Thoden WR, Baybutt RI. Caffeine as an analgesic adjuvant. A double-blind study comparing aspirin with caffeine to aspirin and placebo in patients with sore throat. Arch Intern Med. 1991 April; 151:733-7. [PubMed ID: 2012456]



To investigate the adjuvant analgesic properties of caffeine.


Randomized, double-blind, controlled trial.


A family practice in Savannah, Georgia, USA.


207 adult patients (mean age 30 y) were included who sought treatment for an upper respiratory tract infection with an acute sore throat (with severe pain as measured by the Sore Throat Pain Intensity Scale) and who had objective evidence of tonsillopharyngitis. Exclusion criteria included history of allergic hypersensitivity to aspirin, use of "cold medication" within 8 hours, or consumption of caffeine-containing medication or beverage within 12 hours. 1 patient did not complete treatment because of nausea and vomiting.


Patients were randomly assigned to receive a single dose of 800 mg of aspirin with 64 mg of caffeine (n = 70), 800 mg of aspirin (n = 68), or placebo (n = 69). Assessments were made after 15, 30, 45, 60, 90, and 120 minutes for change in pain, measured on a 6-category scale, and for sore throat pain intensity, relief of pain, how swollen the throat felt, and degree of difficulty in swallowing, all measured using visual analog scales.

Main outcome measure

Change in sore throat pain.

Main results

Aspirin with caffeine was better than aspirin alone for summary measurements of reduction in pain intensity, pain relief, change in pain, change in difficulty swallowing, and change in degree of swollen throat (all comparisons P < 0.05), and both were better than placebo (all comparisons P < 0.01). Increments in overall analgesia for aspirin-caffeine compared with aspirin alone were 44% for reduction in pain intensity, 34% for total pain relief, 34% for change in pain, 33% for change in difficulty swallowing, and 23% for change in swollen throat. Both aspirin regimens were better than placebo for all measurements 30 minutes after treatment and thereafter (P < 0.01). Aspirin with caffeine provided more relief at 15 minutes than did placebo (P < 0.05). Aspirin with caffeine was also better than aspirin alone at 30 minutes (P < 0.05) and thereafter (P < 0.01) on the pain intensity, pain relief, change in pain, and difficulty swallowing scales, and at 90 (P < 0.01) and 120 minutes (P < 0.05) on the swollen throat scale. In 100 patients with oral temperatures > 37°C before treatment, aspirin, with and without caffeine, was equally effective as an antipyretic and was more effective than placebo (P < 0.01).


800 mg of aspirin with 64 mg of caffeine was more effective than 800 mg aspirin alone in reducing sore throat pain, and both were more effective than placebo.

Source of funding: Whitehall Laboratories.

Address for article reprint: Medical Department, Whitehall Laboratories, 685 Third Avenue, New York, NY 10017-4076, USA.


This study showed that aspirin plus caffeine is superior to aspirin alone in providing acute relief of sore throat pain, odynophagia, and a sensation of throat swelling. Symptoms improved on aspirin alone but superior pain relief began at 30 minutes after ingestion and continued for the next 1.25 hours when caffeine was administered with aspirin. The pain relief curves remained close together during the first 45 minutes of the observation period, then splayed apart. These time variable differences serve as an internal control for the validity of the pain evaluation methods used. The use of a randomized, double-blind design was an important methodologic strategy. The benefit derived from the aspirin and caffeine combination was observed across all evaluation measures. The 64-mg dose of caffeine did not appear to have adverse effects. The mechanism of improved analgesia is not defined by the study. Either increased aspirin absorption and bioavailability or some interaction of aspirin and caffeine in the central nervous system may be responsible.

This study provides data that indicate use of preparations containing aspirin and caffeine are likely to provide superior sore throat relief compared with administration of aspirin alone. The results have general applicability to ambulatory medical practice, and the combination of caffeine and aspirin warrants testing in other situations where aspirin is the drug of choice for pain relief.

Stanley L. Wiener, MD
University of IllinoisChicago, Illinois, USA