Patients undergoing major amputation for peripheral arterial disease are at high risk for developing major depressive disorder and requiring long-term antidepressants

Objective: Amputation is an undesirable outcome of severe peripheral artery disease (PAD), which affects both the mobility and broader lifestyle of the patient. Prior studies have shown that lower extremity amputation is associated with increased risk of developing depression in the postoperative period. However, these studies are primarily single-center studies, confined to specific populations, or do not include analysis over various timepoints. The objective of this study was to assess the association between lower extremity amputation level, level of amputation, and postoperative development of depression. This information will allow vascular surgeons to identify patients who are at a high risk for the development of depression after amputation and make the necessary psychiatric referrals. Methods: A total of 48,568 adult patients who underwent PAD-related lower extremity amputation were identified from the TriNetX Research database following exclusion of those with preoperative depression or use of antidepressants. Propensity score matching was used to develop comparable major amputation (above- and below-knee amputations) (I) and minor amputation cohorts (toe and foot amputations) (II), yielding two groups each with 14,853 patients. Primary outcomes included postoperative diagnosis of major depressive disorder (MDD), prescription of antidepressants, and mortality. Outcomes were analyzed at 6-month and 1-year timepoints. Results: Analysis at 6 months demonstrated that major amputation was associated with a higher risk of developing MDD (6.3% vs 4.6%; P value < .001) and requiring antidepressants (26.8% vs 15.8%; P value < .001) when compared with minor amputation. At 1 year, the incidence of MDD, antidepressant prescriptions, and mortality was 7.7% vs 6.4% (P < .001), 28.6% vs 18.5% (P < .001), and 20.7% vs 12% (P < .001), respectively. Additionally, the 1-year mortality rate was 10.8% vs 21.5% vs 20.7% for the Minor, Minor Followed by Major, and Major amputation groups, respectively. The incidence of MDD diagnosis and antidepressant prescriptions was 5.8% vs 11.4% vs 7.7% (P < .001) and 16.9% vs 32% vs 28.6% (P < .001), for the Minor, Minor Followed by Major and Major amputation groups, respectively. Conclusions: The prevalence of MDD and antidepressant medication requirements increases over time in the postoperative period for both major and minor amputees. Patients who underwent major amputations and major amputations after minor amputations were more likely to experience postoperative MDD and require antidepressant prescriptions than patients who underwent minor amputation alone. This suggests that vascular surgeons should understand the high incidence of depression in patients undergoing major amputations and should have a low threshold for referral of major amputees to psychiatric experts in the postoperative period.