Codeine for Pain Related to Osteoarthritis of the Knee and Hip: A Review of Clinical Effectiveness

Key Message

Two systematic reviews with meta-analyses and three randomized controlled trials were identified regarding the clinical effectiveness of codeine with or without acetaminophen or ibuprofen for patients with pain related to osteoarthritis of the knee or hip. While one systematic review did not contain primary studies relevant to this report, one systematic review contained three randomized controlled trials relevant to this report. Although pooled results from one systematic review with meta-analysis suggested that, compared to placebo or no codeine, codeine has a moderate benefit for pain and function in patients with osteoarthritis pain of the knee or hip, codeine resulted in a significantly higher risk for withdrawal due to adverse events. Furthermore, findings from one randomized controlled trial suggested a significantly reduced need for rescue pain medications in the codeine controlled-released versus control group, while two randomized controlled trials did not detect significant differences between codeine plus acetaminophen or ibuprofen versus control groups for this outcome. Finally, findings from all three randomized controlled trials suggested higher rates of adverse events (e.g., nausea, constipation) in codeine versus control groups, with significant differences detected in two randomized controlled trials. Although the systematic reviews were generally well-conducted, the limitations of the included literature (e.g., respiratory depression incidence not reported in systematic reviews and primary studies, co-authors from the drug manufacturer in one primary study, short follow-up durations for all three primary studies) should be considered when interpreting these results. Furthermore, there was a lack of recently conducted primary studies published after 2000, as well as studies comparing codeine with or without acetaminophen or ibuprofen with different opioids or non-steroidal anti-inflammatory drugs other than ibuprofen. Finally, there was a limited quantity of evidence for each of the specific codeine combinations (i.e., codeine alone, codeine plus acetaminophen, codeine plus ibuprofen).