Associations Between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus

Comorbid depression in patients with diabetes deteriorates the prognosis. Antidepressants might attenuate the adverse effects of depression; however, they are associated with cardiometabolic adverse effects.This study aimed to explore the association between antidepressant treatment and advanced diabetic complications and mortality among patients with depression and diabetes mellitus.We conducted a nationwide retrospective cohort study of 36 276 patients with depression and newly treated diabetes mellitus using Taiwan's universal health insurance database. Antidepressant treatment patterns within a 6-month window were classified into none, poor, partial, and regular use, and we accounted for time-dependent variables in the Cox proportional hazards regression analysis with adjustment for time-dependent comorbidity and concomitant use of medications. Different classes of antidepressants were compared. Macro- and microvascular complications, as well as all-cause mortality, were the main outcomes. Benzodiazepines were chosen as negative control exposure.Compared with poor use of antidepressants, regular use was associated with a 0.92-fold decreased risk of macrovascular complications and a 0.86-fold decreased risk of all-cause mortality but not associated with microvascular complications. Regular use of selective serotonin reuptake inhibitors was associated with a 0.83- and 0.75-fold decreased risk of macrovascular complications and all-cause mortality, respectively. Regular use of tricyclic or tetracyclic antidepressants was associated with a 0.78-fold decreased risk of all-cause mortality. Regular use of benzodiazepine showed no association with diabetic outcomes.Regular antidepressant use was associated with lower risk of advanced diabetic complications compared with poor adherence. Clinicians should emphasize antidepressant treatment adherence among patients with depression and diabetes mellitus.