Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
A single dose of codeine 60 mg provides poor analgesia in adults having acute moderate to severe pain.
For acute moderate to severe postoperative pain in adults, is a single dose of codeine 60 mg an effective and safe analgesic as compared to placebo?
The authors conducted a high-quality systematic review of studies to November 2009, utilizing four electronic databases. A defined protocol was followed with two independent authors assessing trial quality and extracting data. Efficacy was assessed using the number of participants achieving at least 50 percent pain relief across four to six hours, and the number requiring rescue medication over a specified time period. Numbers needed to treat (NNT) were calculated with 95 percent confidence intervals. Time to use of rescue medication was sought as a measure of duration of analgesia. Information on adverse events and withdrawals was also collected.
Thirty-five studies evaluated codeine 60 mg (1,223 participants), codeine 90 mg (27 participants), and placebo (1,252 participants). Combining all types of surgery in 33 studies of 2,411 participants, codeine 60 mg had an NNT of 12 (8.4 to 18) for 50 percent pain relief over four to six hours. Following dental surgery, the NNT was 21(12 to 96) in 15 studies of 1,146 participants. The mean time of recue medication was 2.7 hours with codeine and 2.0 hours with placebo. More participants experienced adverse events with codeine 60 mg than placebo, although the difference was not significant and none were serious. Higher doses of codeine (90 mg) were not evaluated due to insufficient data.
Although single-dose codeine 60 mg provides good analgesia to some patients, especially after dental surgery, it does not compare favorably with commonly used alternatives such as acetaminophen, nonsteroidal anti-inflammatory agents (NSAIDs) and their combinations with codeine.
Source of Funding:
Oxford Pain Research funds, UK, NHS Cochrane Collaboration Programme Grant Scheme, UK, NIHR Biomedical Research Centre Programme, UK.
Importance and Context:
Codeine, a controlled drug in the USA which may be over-the-counter in parts of the world, is administered intramuscularly or by mouth, usually in combination with acetaminophen. Codeine, like all opioids, may impair mental or physical abilities required for performance, such as driving. Common adverse effects observed with codeine are drowsiness, constipation and nausea, which may limit its usefulness. Codeine has dose-related adverse effect of respiratory depression. In severe pain, large amounts of codeine are required and repeated administration can cause dependence and tolerance. Evaluation of the analgesic efficacy and safety of codeine for acute pain relief is needed especially for dental surgery procedures.
Strengths and Weaknesses of the Systematic Review:
This high-quality systematic review included a comprehensive search, defined inclusion and exclusion criteria and no language restrictions. The authors manually searched the reference lists of retrieved studies. They did not search abstracts, conference proceedings and grey literature, nor did they contact manufacturers. Two authors independently assessed trial quality and extracted data with disagreements resolved by consensus or by a third author. They followed QUORUM guidelines for data analysis and standard heterogeneity tests. The authors declared receiving contributions for lectures, consultations and research with unnamed pharmaceutical companies, charities, government and industry sources unrelated to this work.
Strengths and Weaknesses of the Evidence:
The included studies, most of which were high quality, were randomized, double-blinded, but small. Twelve studies did not present a sound description of the methods of randomization and double blinding. Two studies inadequately reported data on withdrawals and exclusions. The authors did not assess studies for risk of bias based on randomization, allocation and blinding. Additionally, they were unable to assess the efficacy of multiple doses. Large, long-term epidemiological studies would provide a more accurate assessment of adverse effects due to the problematic reporting during single dosing.
Implications for Dental Practice:
A single dose of codeine 60 mg is a poor analgesic to relieve moderate to severe pain from dental procedures. Based on the available data, only one out of 21 subjects received adequate analgesia using this dosage. Codeine combined with acetaminophen, a Schedule Class III drug, has considerably enhanced analgesia when compared to codeine, a Schedule Class II drug. Nonsteroidal anti-inflammatory agents or even acetaminophen alone are superior to codeine.(1) Non-prescription NSAIDs have the advantages of superior pain relief after dental procedures, lower cost, and no mental impairment.
1. Ong CK, Lirk P, Tan CH, Seymour RA. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin Med Res 2007;5(1):19–34.