Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial

Abstract

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.

Around-the-Clock, Controlled-Release Oxycodone Therapy for Osteoarthritis-Related Pain

“…Results of our studies in patients with moderate to severe osteoarthritis pain support those of previous controlled trials 26,27 demonstrating the analgesic efficacy of CR opioids for treating chronic noncancer pain and pre- vious clinical experience [20][21][22][23][24][25] demonstrating that some patients with noncancer pain benefit from the pain relief offered by opioids without a deterioration in function. Management of chronic osteoarthritis pain requires nonpharmacological and pharmacological approaches.…”

“…One double-blind, 7-day, placebocontrolled crossover study 26 (with subsequent 19-week open evaluation) found that controlled-release (CR) codeine administration reduced pain and pain-related disability in patients with chronic nonmalignant pain, 43.3% of whom had rheumatic pain. Another randomized, double-blind, 9-week crossover study 27 compared CR morphine sulfate therapy with active placebo use in patients with treatment-resistant chronic regional soft tissue or musculoskeletal pain.…”

Attitudes Toward Opioid Use for Chronic Pain: A Canadian Physician Survey

“…pain can reduce pain intensity and improve functioning (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Increased prescribing of opioids between 1990 and 1996 in North America did not result in increased abuse, supporting the idea that it is not exposure to opioids alone that causes addiction but rather a complex interplay of biopsychosocial factors (16).…”

Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects

“…The few studies in our review that collected such data were relatively short for the observation of any endocrinological abnormalities. The only 2 studies 29,32 that reported data on sexual function showed that patients taking opioids actually perceived themselves as doing better in terms of sexual behaviour compared with those in the control groups. Improvement of wellbeing secondary to better pain control may account for this result: the PDI is a patient-rated global rating of function and does not measure variables such as libido, sexual dysfunction or gonadal function, and cannot be used to estimate the risk of hypogonadism.…”