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The following is a summary of the “Patients Undergoing Major Amputation for Peripheral Arterial Disease Are at High Risk for Developing Major Depressive Disorder and Requiring Long-Term Antidepressants,” published in the March 2025 issue of the Journal of Vascular Surgery by Lavanga et al.

Lower extremity amputation is a significant and often unavoidable consequence of advanced peripheral artery disease (PAD), profoundly affecting patients’ mobility, quality of life, and psychological well-being. Prior research has suggested an increased risk of depression following amputation; however, existing studies are often limited by single-center data, restricted populations, or a lack of long-term analysis. 

This study aimed to evaluate the association between amputation level and the subsequent development of major depressive disorder (MDD), providing insight into patients with high risk who may benefit from early psychiatric intervention. A retrospective analysis was conducted using the TriNetX Research database, identifying 48,568 adult patients who underwent PAD-related lower extremity amputation. Patients with preoperative depression or prior antidepressant use were excluded. Propensity score matching was employed to create two balanced cohorts: a major amputation group (above- and below-knee amputations) and a minor amputation group (toe and foot amputations), each consisting of 14,853 patients. 

Primary outcomes included the postoperative diagnosis of MDD, prescription of antidepressants, and mortality, analyzed at 6-month and 1-year time points. At 6 months, patients undergoing major amputation exhibited a significantly higher risk of developing MDD (6.3% vs. 4.6%, p < 0.001) and requiring antidepressant prescriptions (26.8% vs. 15.8%, p < 0.001) compared to those undergoing minor amputations. At 1 year, major amputees continued to show increased incidence of MDD (7.7% vs. 6.4%, p < 0.001), greater antidepressant use (28.6% vs. 18.5%, p < 0.001), and higher mortality (20.7% vs. 12%, p < 0.001). Further subgroup analysis revealed that patients who underwent a minor amputation followed by a subsequent major amputation experienced the highest rates of MDD (11.4%) and antidepressant use (32%) at 1 year, compared to those who underwent only minor (5.8% and 16.9%) or only major amputations (7.7% and 28.6%) (p < 0.001). The 1-year mortality rates were 10.8% for minor amputees, 21.5% for patients with a minor amputation followed by a major amputation, and 20.7% for major amputees. 

These findings indicate that patients undergoing major amputations, particularly those requiring major surgery after an initial minor amputation, face a significantly elevated risk of postoperative depression and antidepressant use. Given the progressive increase in MDD prevalence and medication use over time, vascular surgeons should be proactive in identifying patients at risk and facilitating early psychiatric referrals to optimize postoperative mental health outcomes.

Source: jvascsurg.org/article/S0741-5214(25)00617-2/abstract