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

CONTEXT: 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. OBJECTIVE: This study aimed to explore the association between antidepressant treatment and advanced diabetic complications and mortality among patients with depression and diabetes mellitus. METHODS: 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. RESULTS: 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. CONCLUSION: 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.