Association between perioperative antidepressant use and postoperative outcomes after cutaneous melanoma resection

Cutaneous melanoma is the fifth most common cancer in the USA and the most fatal form of skin cancer. Antidepressants (ADPs) are among the most commonly prescribed medications in this population and may influence postoperative recovery through effects on platelet aggregation, immune signaling, and pain modulation. This study aimed to determine whether perioperative ADP use is associated with increased postoperative complications and healthcare utilization following melanoma resection. Using the TriNetX federated database, we conducted a propensity-matched retrospective cohort study comparing 90-day postoperative outcomes between adult melanoma patients with and without perioperative ADP use following surgical resection. Among 19 470 propensity-matched patients (9735 per group), ADP use was associated with significantly higher rates of opioid prescriptions (32.8% vs 21.2%), surgical site infection (2.1% vs 1.1%), sepsis (1.2% vs 0.4%), inpatient hospitalization (10.7% vs 5.2%), emergency department visits (6.9% vs 4.5%), and hemorrhage (0.3% vs 0.1%; all P  < 0.01). Patients in the control cohort were more likely to undergo lymph node biopsy than ADP users (1.3% vs 0.9%; P  = 0.006). Wound disruption did not differ significantly between groups. Perioperative ADP use was associated with increased postoperative morbidity and healthcare utilization. Because tumor characteristics and procedural complexity could not be assessed in this dataset, these findings are best interpreted as identifying ADP use as a marker of a higher-risk perioperative phenotype rather than evidence of a direct causal effect. These results support proactive monitoring, infection surveillance, and judicious opioid prescribing in this population.