Analgesic benefit of metamizole and ibuprofen vs. either medication alone: a randomized clinical trial

Postoperative pain relief remains a key problem after surgery. Multimodal pain therapy has proven beneficial in alleviating pain to a certain extent. However, when combining non-opioids, the focus has been on NSAIDs and paracetamol, but effects of combined use are only moderate. Metamizole could be a potent adjunct, due to its preclusion in several countries, data on its combined use are sparse, despite its common use in many countries. The aim of this study was to examine whether the combination of metamizole and ibuprofen is superior in relieving postoperative pain to either drug alone.

For this randomized, placebo-controlled, cross-over study, 35 patients undergoing bilateral lower third molar extraction were randomized. Each patient received three applications of 1000 mg metamizole + 400 mg ibuprofen for surgery on one side and either 1000 mg metamizole + placebo or 400 mg ibuprofen + placebo on the other side. Pain ratings, rescue-medication (tramadol), and sleep were assessed for 18 hours.

The combined treatment of metamizole and ibuprofen showed lower mean pain scores over 12 hours than ibuprofen (2.4±1.3 vs 3.8±1.6; P=0.005). Further, combined treatment showed lower mean pain scores over 6 hours than ibuprofen (2.0±1.2 vs. 3.1±1.6; P=0.022) or metamizole alone (2.0±1.2 vs. 3.3±1.7; P=0.015). Consumption of rescue medication was lowest in the combination-group (25% vs. 46%-metamizole; 50%-ibuprofen). The trial was stopped prematurely as the COVID-pandemic halted elective surgeries.

Combined use enables superior pain control compared to ibuprofen after molar extraction and tends to be superior to metamizole alone. The premature study-termination may overestimate this effect.