Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study

Abstract

This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients.

Opioid Therapy for Chronic Nonmalignant Pain

“…These studies, which have usually assayed codeine or a similar drug in arthritic patients, yielded mixed results and have questionable relevance to long term treatment (81)(82)(83). None has identified a problem with aberrant drug-related behaviours during this brief period of treatment.…”

The DIRE Score: Predicting Outcomes of Opioid Prescribing for Chronic Pain

“…12,35,36,43,44,45,47 This concept was a natural outgrowth of the use of opioids for acute and cancer pain. Subsequent data from multiple case series 17,24,27,42,50,51 and randomized controlled trials 3,5,7,8,13,15,16,19,20,25,26,28,29,30,34,37,39,40,41,48 have supported the use of opioids for this problem; and established medical bodies have developed guidelines supporting opioid use. 4,11,21 In recent years, however, the acceptance of the use of opioids for chronic noncancer pain has been tempered by increasing fears of misuse and safety issues.…”

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

“…However, when sensitivity analysis was conducted based on the type of opioids, the strong opioids (oxycodone, morphine) were significantly more effective than other drugs for pain relief (SMD -0.34, 95% CI -0.67 to -0.01). One trial 16 not included in the meta-analysis showed that the addition of codeine to a regimen of acetaminophen was superior to acetaminophen alone at 7 days of follow-up, but not afterward.…”