Affiliation:
1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
2. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
3. Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom
Abstract
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.
Funder
the Strategic Research Area Neuroscience at Karolinska Institutet
Vetenskapsrådet
Center for Innovative Medicine
Hjärt-Lungfonden
Loo och Hans Ostermans Stiftelse för Medicinsk Forskning
Stiftelsen Stig och Gunborg Westman
Martin Rinds Stiftelse
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Transplantation,Nephrology,Critical Care and Intensive Care Medicine,Epidemiology