Adverse events of oral analgesics after third molar extraction: A network meta-analysis of randomized controlled...

Choosing analgesics after third molar surgery requires balancing efficacy with safety. This network meta-analysis (NMA) aimed to compare and rank the safety profiles, measured by adverse events (AEs) related to medication use, of various single-dose oral analgesic regimens.

Electronic databases were searched for randomized controlled trials (RCTs) assessing single-dose oral analgesics following third molar surgery. The primary outcome was the incidence of any AE reported before discharge. A frequentist NMA was performed to estimate relative risks (RR) and SUCRA-based probabilistic rankings. The certainty of the evidence was assessed using CINeMA.

Twenty-eight RCTs involving 5306 patients were included. NSAID monotherapy demonstrated a significantly higher risk of AEs compared to other non-opioid analgesics and opioid analgesics alone. Conversely, few significant differences were found between most active drugs and placebo. Probabilistic ranking indicated that both nonsteroidal anti-inflammatory drugs (NSAIDs) and placebo had a higher probability of ranking among the least safe options. Significant global inconsistency was detected across the network, and the certainty of the evidence was generally very low to low.

The safety profile of single-dose analgesics in this model is complex. While pairwise comparisons and rankings suggested that NSAIDs might be associated with a higher frequency of adverse events, these findings are based on very low to low certainty evidence and likely reflect minor, transient events such as nausea. Additionally, the high incidence of events in the placebo group suggests that the nocebo effect plays a predominant role in event perception. Therefore, results regarding the comparative safety of NSAIDs should be interpreted with caution, balancing this potential risk against their superior analgesic efficacy.