Comparative Safety of Antidepressants in Adults with CKD

Background Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains unclear.Methods We identified adults with CKD stages G3-5 (eGFR <60 ml/min per 1.73 m2 not treated with dialysis) and incident depression diagnosis during 2007-2019 from the Stockholm Creatinine Measurements project. Using the target trial emulation framework, we compared the following treatment strategies: (1) initiating versus not initiating antidepressants, (2) initiating mirtazapine versus selective serotonin reuptake inhibitors (SSRIs), and (3) initiating SSRIs with a lower dose versus a standard dose.Results Of 7798 eligible individuals, 5743 (74%) initiated antidepressant treatment. Compared with noninitiation, initiation of antidepressants was associated with higher hazards of short-term outcomes, including hip fracture (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.88 to 1.74) and upper gastrointestinal bleeding (HR, 1.38; 95% CI, 0.82 to 2.31), although not statistically significant. Initiation of antidepressants was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular event, CKD progression, and suicidal behavior. Compared with SSRIs, initiation of mirtazapine was associated with a lower hazard of upper gastrointestinal bleeding (HR, 0.52; 95% CI, 0.29 to 0.96), but a higher hazard of mortality (HR, 1.11; 95% CI, 1.00 to 1.22). Compared with the standard dose, initiation of SSRIs with a lower dose was associated with nonstatistically significantly lower hazards of upper gastrointestinal bleeding (HR, 0.68; 95% CI, 0.35 to 1.34) and CKD progression (HR, 0.80; 95% CI, 0.63 to 1.02), but a higher hazard of cardiac arrest (HR, 2.34; 95% CI, 1.02 to 5.40).Conclusions Antidepressant treatment was associated with short-term adverse outcomes but not long-term outcomes in people with CKD and depression.