Nonopioid vs opioid analgesics after impacted third-molar extractions: The Opioid Analgesic Reduction Study randomized clinical trial

Abstract

Background: Opioids are still being prescribed to manage acute postsurgical pain. Unnecessary opioid prescriptions can lead to addiction and death, as unused tablets are easily diverted.

Methods: To determine whether combination nonopioid analgesics are at least as good as opioid analgesics, a multisite, double-blind, randomized, stratified, noninferiority comparative effectiveness trial was conducted, which examined patient-centered outcomes after impacted mandibular third-molar extraction surgery. Participants were randomized to receive 5 mg of hydrocodone with 300 mg of acetaminophen (opioid) or 400 mg of ibuprofen and 500 mg of acetaminophen (nonopioid). After an initial dose, analgesic was taken every 4 through 6 hours as needed for pain.

Results: In this randomized multisite clinical trial (n = 1,815 adults), those not taking opioids experienced significantly less pain (numeric rating scale ranging from 0 [no pain] through 10 [worst pain imaginable]) for first day and night (mean difference, -0.70; 95% CI, -0.94 to -0.45; P < .001) and second day and night (mean difference, -0.28; 95% CI, -0.52 to -0.04; P = .015), and experienced no more pain than participants taking opioids over the entire postoperative period (mean difference, -0.20; 98.75% CI, -0.45 to 0.05; P = .172). Participants not taking opioids had higher overall satisfaction at the postoperative visit (85.3% extremely satisfied or satisfied vs 78.9%; 95% CI, 1.21 to 1.98; P = .006).

Conclusions: The ibuprofen and acetaminophen combination managed pain better for the first 2 days and led to greater satisfaction over the entire postoperative period than hydrocodone with acetaminophen. At no time did hydrocodone outperform the nonopioid.

Practical implications: Routine opioid prescribing after dental surgery is not supported. The results of this study confirmed the American Dental Association's recommendations that ibuprofen and acetaminophen in combination should be the first-line therapy for acute pain management. This clinical trial was registered at ClinicalTrials.gov. The registration number is NCT04452344.

Keywords: Pain management; addiction; ibuprofen and acetaminophen; impacted mandibular third-molar extraction; nonopioids; opioids.