Risk of Overdose and Adverse Events With Concomitant Opioids and Gabapentinoid Use After Total Joint Arthroplasty

PURPOSE: We evaluated the safety outcomes of opioids alone versus opioids plus low-dose gabapentinoids in patients naïve to both opioids and gabapentinoids, after total joint arthroplasty (TJA) of the knee, hip, or shoulder. METHODS: This was a multicenter, population-based, retrospective cohort study based in a large, integrated health system. It included opioid-naïve and gabapentinoid-naïve patients who underwent TJA between 2018 and 2024. Patients were categorized into two groups: those dispensed opioids and low-dose gabapentinoids or those dispensed opioids alone postoperatively. The primary outcome was opioid-related overdose events. The secondary outcome was adverse events, including falls, fractures, neurologic/cognitive changes, sedation, and delirium. RESULTS: In total, 36,351 consecutive patients comprised the study cohort, including 29,009 (79.8%) in the opioids-alone group and 7,342 (20.2%) in the opioids plus gabapentinoids group. In total, there were 19 (0.05% total cohort) opioid-related overdose events. Fourteen of these (0.05%) were in the opioids-alone group, and five (0.07%) were in the opioids plus gabapentinoids group (P = 0.3). In addition, 233 patients (0.6%) experienced emergency department or hospital admission due to an adverse event, including 200 patients (0.69%) in the opioids-alone group and 33 patients (0.45%) in the opioids plus gabapentinoids group. No statistically significant difference in adverse event risk was identified between groups. CONCLUSION: Concurrent prescriptions for opioids and low-dose gabapentinoids after TJA were not associated with a statistically significant difference in risk of emergency department or hospital readmission due to opioid-related overdose or adverse events compared with opioids alone. However, the rarity of overdose events limits statistical power, and these findings should be interpreted cautiously.