Association between antidepressants and the risk of diabetic foot ulcers and amputation in antidepressant-naïve type 2 diabetes mellitus patients: A nested case-control study

Abstract

AimsAntidepressants are widely used by individuals with type 2 diabetes mellitus (T2DM). This study aimed to explore the correlation between antidepressant use, considering specific antidepressant subclasses or cumulative doses, and diabetic foot ulcer (DFU) risk. MethodsThis nested case-control study was conducted using a representative population-based Korean cohort database from 2002 to 2019. Participants with DFUs were matched with participants without DFUs based on age, sex, date of T2DM diagnosis, and follow-up duration. In total, 791 DFUs and 3900 controls were included. The association between antidepressant use or cumulative dose of each antidepressant subclass, DFU risk and amputation risk was examined using a conditional logistic regression model. ResultsAntidepressant ever-use was associated with an increased incidence of DFUs compared with non-use. Furthermore, an increase in DFU risk was evident with increasing cumulative antidepressant dosage, particularly among tricyclic antidepressant (TCA) ever-users and selective serotonin reuptake inhibitors (SSRIs) ever-users. Additionally, antidepressant ever-users displayed a higher risk of DFUs requiring amputation, which was consistently observed when the cumulative dosages of overall antidepressants and TCAs were considered. ConclusionCaution is advised when administering TCAs and SSRIs in antidepressant-naïve T2DM patients to reduce DFU and the consequent amputation risk.