Assessment of the efficacy and safety profiles of aspirin and acetaminophen with codeine: results from 2 randomized, controlled trials in individuals with tension-type headache and postoperative dental pain

Clin Ther. 2012 Jan;34(1):138-48. doi: 10.1016/j.clinthera.2011.11.018. Epub 2011 Dec 14.


Background: Aspirin is a widely used NSAID that has been extensively studied in numerous conditions. Nonprescription analgesics, such as aspirin, are frequently used for a wide variety of common ailments, including conditions such as dental pain and tension-type headache.

Objective: We sought to compare the efficacy and safety profiles of aspirin, acetaminophen with codeine, and placebo in the treatment of post-operative dental pain and tension-type headache.

Methods: These were 2 randomized, double-blind, placebo-controlled, single-dose clinical trials that assigned participants (2:2:1) to receive either aspirin (1000 mg), acetaminophen (300 mg) with codeine (30 mg), or placebo. The primary efficacy end point was the sum of pain intensity differences from baseline (SPID) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study. Other common analgesic measures, in addition to safety, were also evaluated.

Results: The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points. Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0-4) (P = 0.028). In the tension-type headache study, aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo for SPID(0-4) and SPID(0-6) (P < 0.001) and for total pain relief (P < 0.001). There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID (P ≥ 0.070), complete relief (P ≥ 0.179), or time to meaningful relief (P ≥ 0.245). Regarding safety, there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies.

Conclusions: These 2 randomized, double-blind, placebo-controlled studies demonstrate that treatment with aspirin (1000 mg) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen (300 mg) with codeine (30 mg) therapy after impacted third molar extraction and in tension- type headache.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / adverse effects
  • Acetaminophen / therapeutic use*
  • Adolescent
  • Adult
  • Aged
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / therapeutic use*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Analysis of Variance
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Codeine / adverse effects
  • Codeine / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain Measurement
  • Pain, Postoperative / diagnosis
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / etiology
  • Tension-Type Headache / diagnosis
  • Tension-Type Headache / drug therapy*
  • Time Factors
  • Tooth Extraction / adverse effects*
  • Treatment Outcome
  • United States
  • Young Adult


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • acetaminophen, codeine drug combination
  • Acetaminophen
  • Aspirin
  • Codeine