PSY3 OPIOIDS IN NON-MALIGNANT PAIN: ARE THEY EQUIVALENT IN SAFETY PROFILE? A NETWORK META-ANALYSIS

Abstract

Severe non-malignant pain affects a large number of patients. Opioids are an important option for analgesia. However, there is relatively little information about the comparative safety of opioids. We sought to compare the safety and tolerability of commonly used opioids in non-malignant pain through network meta-analyses of randomized controlled trials (RCTs). Medline and Embase were searched from 2000 to 2011 for RCTs comparing commonly used opioids (tramadol, oxycodone, hydrocodone, propoxyphene, codeine) in non-malignant pain. Studies were assessed for inclusion/exclusion based on a prespecified protocol. Two reviewers undertook data extraction independently. Any disagreement was resolved by a third reviewer. A network meta-analysis was used to combine direct and indirect evidence for safety outcomes reported in the trials. Based on the incidence of adverse events (AEs) for each intervention, a probability-based ranking (probability (P) of being worst) was generated using WinBUGS. Of the 1156 studies, 5 RCTs enrolling 1399 patients were eligible for inclusion. The most commonly reported AEs were nausea, vomiting, somnolence, dizziness, headache, constipation and dry mouth. Withdrawals due to AEs were most commonly observed with codeine (P=42%) followed by hydrocodone (P=28%), tramadol (P=19%), and oxycodone (P=10%). The probability of occurrence of nausea and somnolence was the highest with codeine. Dizziness was most frequently associated with oxycodone (P= 53%). However, the incidence of dizziness and headache was the lowest with codeine. Tramadol was observed to be associated with the highest (P=40%) incidence of vomiting, while hydrocodone had the lowest incidence (P=15%). Codeine was observed to have the highest incidence of withdrawals due to AEs. It was observed that the probability of occurrence of any particular AE varied across included opioid analgesics. Codeine was observed to have been more frequently associated with nausea/somnolence while tramadol and oxycodone had the highest incidence of vomiting and dizziness respectively.