ANALGESIC EFFICACY AND SAFETY OF PARACETAMOL-CODEINE COMBINATIONS VERSUS PARACETAMOL ALONE - A SYSTEMATIC REVIEW

Objectives-To assess whether adding codeine to paracetamol has an addi tive analgesic effect; to assess the safety of paracetamol-codeine com binations versus paracetamol alone. Design-Systematic literature revie w with meta-analysis, methodological quality of published trials being scored by means of 13 predefined criteria. Trials-24 of 29 trials tha t met the inclusion criteria. Models studied in the trials were postsu rgical pain (21), postpartum pain (one), osteoarthritic pain (one), an d experimentally induced pain (one). Interventions-Dosages ranged from 400 to 1000 mg paracetamol and 10 to 60 mg codeine. Main outcome meas ures-The sum pain intensity difference (efficacy analysis) and the pro portion of patients reporting a side effect (safety analysis). Results -Most trials were considered of good to very good quality. Only the si ngle dose studies could be combined for analysis of analgesic efficacy . Pooled efficacy results indicated that codeine added to paracetamol provided a 5% increase in analgesia on the sum pain intensity differen ce. This effect was comparable to the difference in analgesic effect b etween codeine and placebo. The cumulative incidence of side effects w ith each treatment was comparable in the single dose trials. In the mu ltidose studies a significantly higher proportion of side effects occu rred with paracetamol-codeine preparations. Conclusion-The difference in analgesic effect between paracetamol-codeine combinations and parac etamol alone was small but statistically significant. In the multidose studies the proportion of patients reporting a side effect was signif icantly higher with paracetamol-codeine combinations. For occasional p ain relief a paracetamol-codeine combination might be appropriate but repeated use increases the occurrence of side effects.