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

Aims: Antidepressants 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. Methods: This 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. Results: Antidepressant 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) everusers. 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. Conclusion: Caution is advised when administering TCAs and SSRIs in antidepressant -naive T2DM patients to reduce DFU and the consequent amputation risk.