The association of comorbid depression with mortality and amputation risk in patients with chronic limb-threatening ischemia.

ABSTRACT

OBJECTIVE: There is increasing evidence that depression is a risk factor for worse outcomes in patients with peripheral artery disease. The association of depression in patients with chronic limb-threatening ischemia (CLTI) is not well described, nor is the impact of medical treatment for depression in this patient population. The objective of this study was to investigate the prevalence of depression in patients with CLTI, its association on major amputation and all-cause mortality, and whether medical antidepressant treatment is associated with improvement in these outcomes in patients with depression. METHODS: A retrospective review of all adult patients (≥18 years old) diagnosed with CLTI from January 1, 2007, to December 31, 2018, at a single academic medical center was performed. Collected data included patient demographics, comorbidities, and diagnosis of depression within 6 months of initial CLTI diagnosis. We also collected data on use of antidepressant medications. Outcomes evaluated were need for major lower extremity amputation and all-cause mortality. Multivariable logistic regression models estimated the adjusted effects of comorbid depression and antidepressant medication use on major amputation and all-cause mortality. Kaplan-Meier survival curves illustrated the probabilities of survival and limb salvage over time, stratified by diagnosis of comorbid depression. Multivariable Cox proportional hazards models estimated the adjusted effects of comorbid depression on time to major amputation and all-cause mortality, and the adjusted effect of antidepressant treatment on time to all-cause mortality. RESULTS: A total of 2987 patients with CLTI were identified. Mean age was 68.6 years (standard deviation, 12.9 years); 56.5% were male, and 43.5% were female. Comorbid depression within 6 months of CLTI diagnosis was present in 7.1% of the cohort (212 patients). In multivariable analysis, comorbid depression was associated with a 68% increase in the odds of major amputation (adjusted odds ratio [aOR], 1.68; 95% confidence interval [CI], 1.19-2.37; P < .01), a 164% increase in the odds of all-cause mortality among patients not taking antidepressants (aOR, 2.64; 95% CI, 1.31-5.32; P = .03), and only a 6% increase in the odds of all-cause mortality among patients taking antidepressants (aOR, 1.06; 95% CI, 0.72-1.55; P = .99). The effect of comorbid depression on mortality varied significantly by whether or not the patient was taking an antidepressant medication (P = .02). CONCLUSIONS: Comorbid depression in the patient population with CLTI is associated with a worse prognosis for major lower extremity amputation overall, and a worse prognosis for all-cause mortality among patients not taking an antidepressant. Furthermore, antidepressant treatment in the presence of comorbid depression in this patient population is associated with an improvement in the odds of all-cause mortality, illustrating the potential importance of medical management of depression.