Perioperative Antidepressant Use Increases the Risk of Opioid Abuse After Total Joint Arthroplasty

Background: Antidepressants are commonly prescribed in patients undergoing total joint arthroplasty. While depression influences recovery, the association between perioperative antidepressant use and opioid-related outcomes remains unclear. Given the opioid crisis, we examined whether antidepressant exposure around surgery is independently associated with postoperative opioid abuse after total knee (TKA) and hip arthroplasty (THA), along with systemic and prosthetic complications over short-term and long-term follow-up. Methods: We conducted a retrospective cohort study using the TriNetX Research Network (2005-2025). Adults undergoing elective primary TKA or THA were identified using International Classification of Diseases-10/current procedural terminology codes. Patients with antidepressant prescriptions within 3 months before or after surgery were compared with nonusers. Propensity score matching (1:1) balanced demographics, comorbidities, and concurrent medications. Outcomes included opioid abuse diagnoses, opioid prescribing, systemic complications, and prosthetic failures at 90 days and 5 years. Odds ratios (ORs) with 95% CIs were calculated. Results: After matching, 90-day cohorts included 106,516 TKA patients and 46,227 THA patients per group; 5-year cohorts included 44,251 TKA and 16,019 THA patients per group. Despite modest prescribing differences, antidepressant use was associated with higher opioid-abuse diagnoses. At 90 days: TKA 0.10% vs. 0.02% (OR 4.3) and THA 0.12% vs. 0.02% (OR 5.7). At 5 years: TKA 0.74% vs. 0.12% (OR 6.0) and THA 0.42% vs. 0.09% (OR 4.5). Antidepressant users also had increased systemic and prosthetic complications, including prosthetic joint infection, periprosthetic fracture, and revision. Conclusions: Perioperative antidepressant use is independently associated with increased postoperative opioid abuse and higher complication rates after TKA and THA. These findings support preoperative psychiatric screening, medication review, multimodal pain strategies, and closer monitoring to mitigate opioid-related harm in vulnerable arthroplasty patients. Level of evidence: Level III. See Instructions for Authors for a complete description of levels of evidence.