Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain

H. S. Dhaliwal, Paul Sloan, William W. Arkinstall, Michael P. Thirlwell, Najib Babul, Zoltan Harsanyi, Andrew C. Darke

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Codeine is widely used in combination with acetaminophen and aspirin for the management of mild to moderate pain. However, there are few controlled clinical trials of single-entity codeine in chronic cancer pain. The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release codeine given every 12 hr in patients with cancer pain. Thirty-five patients with chronic cancer pain were randomized in a double-blind crossover study to controlled-release (CR) codeine or placebo, for 7 days each. Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale (VAS) and a five-point categorical scale, and the use of "rescue" acetaminophen-plus-codeine (300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients completed the study (17 male, 13 female; mean age, 64.4 ± 9.8 years) with a mean daily CR codeine dose of 277 ± 77 mg (range, 200-400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (22 ± 0.8 mm versus 36 ± 20 mm, P = 0.0001), categorical pain intensity scores (1.2 ± 0.8 versus 1.8 ± 0.8, P = 0.0001), and pain scores when assessed by day of treatment and by time of day. Daily "rescue" analgesic consumption was significantly lower on CR codeine, compared to placebo treatment (2.2 ± 2.3 versus 4.6 ± 2.8 tablets per day, P = 0.0001). Both patients and investigators preferred CR codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7%, P = 0.0160, respectively). These data indicate that CR codeine, given every 12 hr results in significant reductions in pain intensity and the use of "rescue" acetaminophen-plus-codeine in patients with cancer pain. CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action, which allows patients uninterrupted sleep and improved compliance.

Original languageEnglish
Pages (from-to)612-623
Number of pages12
JournalJournal of Pain and Symptom Management
Issue number8
StatePublished - Nov 1995

Bibliographical note

Funding Information:
We acknowledge Drs. Pauline Lavoie, Neii Hagen, and Oscar Wong for participation in the stud),; John Ketflewell and Dr. Elke Clarke for study monitoring; Rebecca Strange for online literature searches and information retrieval; and Dr. T.N. Krishnamurthy for pharmaceutical assistance. Supported by a research grant from Purdue Frederick, Pickering, Ontario


  • Codeine
  • cancer pain
  • clinical efficacy
  • clinical trial
  • controlled-release
  • drug safety
  • drug treatment
  • opioid use

ASJC Scopus subject areas

  • General Nursing
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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