Double blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee

J Rheumatol. 2000 Mar;27(3):764-71.


Objective: Pain is the cardinal feature of osteoarthritis (OA), and with advancing disease there is loss of function and increasing pain even at times of joint rest. Few studies have evaluated the role of opioid analgesics in treating the pain of OA.

Methods: This randomized, double blind, parallel group study compared the efficacy and safety of a 12 hourly controlled release codeine formulation (Codeine Contin) with placebo in patients with chronic pain due to OA of the hips and/or knees. The 4 week treatment period, following an analgesic washout phase of 2-7 days, included weekly clinic evaluations, at which the dose was escalated as appropriate, and daily patient diary completion. Pain (daily), stiffness, and physical function (weekly) were assessed using the multidimensional, self-administered WOMAC (visual analog scale version) questionnaire.

Results: Sixty-six eligible patients completed the study. The mean initial and final daily doses of controlled release codeine were 50 mg every 12 h at baseline and 159 mg every 12 h at the final assessment. All variables in the efficacy analysis indicated superiority of controlled release codeine over placebo. The WOMAC pain scale showed an improvement of 44.8% over baseline in the controlled release codeine group compared with 12.3% taking placebo (p = 0.0004). For the WOMAC stiffness and physical function scales the improvements over baseline on controlled release codeine were 47.7% and 49.3%, respectively compared with 17.0% and 17.0%, respectively, with placebo (p = 0.003; p = 0.0007). Controlled release codeine was also significantly better than placebo on measures of sleep quality and requirement for supplemental acetaminophen.

Conclusion: Single entity controlled release codeine is an effective treatment for pain due to OA of the hip or knee.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / therapeutic use
  • Aged
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / therapeutic use
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / therapeutic use
  • Codeine / administration & dosage*
  • Codeine / therapeutic use
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis, Hip / drug therapy*
  • Osteoarthritis, Hip / physiopathology
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Placebos
  • Pliability
  • Sleep / drug effects


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Placebos
  • Acetaminophen
  • Codeine