Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial.
Treatment decisions for the use of opioid analgesics in chronic non-malignant pain are based primarily on survey data, as evidence from well-controlled clinical trials has been lacking. Forty-six patients with chronic non-malignant pain were enrolled in a randomized, double-blind, placebo-controlled evaluation of controlled-release (CR) codeine. Following a 3-7-day diary familiarization period, patients were randomly assigned to 7 days of treatment each with CR codeine q12h or placebo. The CR codeine dose was determined from the consumption of acetaminophen+codeine in the 7 days preceding the study. During both phases, breakthrough pain was treated with acetaminophen+codeine every 4 h as required. Pain intensity was assessed at 08:00 h and 20:00 h using a visual analogue scale (VAS) and a 5-point categorical scale, and rescue analgesic consumption was recorded at the time of use. Thirty patients (17 female, 13 male; mean age: 55.1 +/- 13.4 years) completed the study and were treated with a mean daily CR codeine dose of 273 +/- 78 mg (range: 200-400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (35 +/- 18 vs. 49 +/- 16, P = 0.0001), categorical pain intensity scores (1.7 +/- 0.6 vs. 2.2 +/- 0.6, P = 0.0001), and in pain scores by day of treatment and by time of day. Daily rescue analgesic consumption was significantly lower on CR codeine, relative to placebo treatment (3.6 +/- 3.5 vs. 6.1 +/- 3.2 tablets/day, P = 0.0001). There was also a significant reduction in the Pain Disability Index (PDI) on CR codeine, compared to placebo (25.0 +/- 7.7 vs. 35.1 +/- 8.2, P = 0.0001). Patients' and investigators' blinded treatment preference was significantly in favor of CR codeine, relative to placebo (73% vs. 10%, P = 0.0160 and 80% vs. 7%, P = 0.0014, respectively). The incidence of nausea was significantly higher on CR codeine than on placebo (32.6% vs. 11.9%, P = 0.013). Ninety-three percent of patients completing the study requested long-term, open-label treatment with CR codeine. Pain intensity scores at the completion of 19 weeks of long-term evaluation were comparable to those during the double-blind CR codeine treatment. We conclude that treatment with CR codeine results in reduced pain and pain-related disability in patients with chronic non-malignant pain.
Arkinstall
William
W
Allergy and Respiratory Medicine Clinic and Kelowna General Hospital, Kelowna, British Columbia V1Y 9L8, Canada Department of Anaesthesia, Toronto Hospital, Toronto General Division Toronto M5G 2C4, Canada Department of Scientific Affairs, Purdue Frederick, Pickering, Ontario L1W 3W8, Canada.
Sandler
Alan
A
Goughnour
Barry
B
Babul
Najib
N
Harsanyi
Zoltan
Z
Darke
Andrew C
AC
D000082:Acetaminophen / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D000704:Analysis of Variance; D002908:Chronic Disease; D003061:Codeine / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy*; D010919:Placebos
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D010919:Placebos; D000082:Acetaminophen; D003061:Codeine