We read with interest “Comparative cardiac safety of selective serotonin reuptake inhibitors among individuals receiving maintenance hemodialysis” by Assimon et al.1 This large retrospective analysis found that patients on hemodialysis who initiated selective serotonin reuptake inhibitors (SSRIs) with higher QT-prolonging potential (citalopram and escitalopram) had a significantly increased risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31) compared with patients who initiated SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, and sertraline). Given the lack of evidence regarding the efficacy of SSRIs for major depressive disorder in patients with advanced kidney disease and the prevalence of premature cardiovascular mortality in this setting, the findings of Assimon et al.1 raise important questions about the use of these agents in this context.
Depression is a common comorbidity among patients with advanced kidney disease,2 although diagnosis is complicated by the overlap of clinical features of these two conditions. Notwithstanding this, depression in this setting is associated with adverse clinical outcomes, including increased mortality risk.3 It is far from clear, however, whether the association is independent of antidepressant use. Three randomized, placebo-controlled trials of SSRIs in individuals with kidney disease4–6 have failed to provide evidence of benefit while signposting increased risks of adverse events (reviewed in ref. 7). A recent randomized trial comparing sertraline with cognitive behavioral therapy in patients on dialysis showed a modest difference in favor of sertraline,8 although there was no control group.
We appreciate that additional randomized, controlled trials are needed in this area and that the study of Assimon et al.1 is not able to provide evidence for the absolute mortality risk associated with antidepressant use. However, we feel that there is a real possibility that, in some patients at least, these agents may be doing more harm than good. Hence, it may be appropriate to consider whether withdrawing antidepressants in suitable patients may be the appropriate strategy. Withdrawal could mean withdrawing one agent and switching to another, withdrawing and switching to a psychological treatment, or stopping all together. Antidepressant withdrawal requires careful risk assessment, patient education and counseling, and a considered tapering regimen to mitigate symptoms of withdrawal.9 We believe that there is a strong case for empirical studies of antidepressant withdrawal in suitable patients with advanced kidney disease.
1. Assimon MM, Brookhart MA, Flythe JE: Comparative cardiac safety of selective serotonin reuptake inhibitors among individuals receiving maintenance hemodialysis. J Am Soc Nephrol 30: 611–623, 2019
2. Palmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al.: Prevalence of depression in chronic kidney disease: Systematic review and meta-analysis of observational studies. Kidney Int 84: 179–191, 2013
3. Chilcot J, Guirguis A, Friedli K, Almond M, Day C, Da Silva-Gane M, et al.: Depression symptoms in haemodialysis patients predict all-cause mortality but not kidney transplantation: A cause-specific outcome analysis. Ann Behav Med 52: 1–8, 2018
4. Blumenfield M, Levy NB, Spinowitz B, Charytan C, Beasley CM Jr, Dubey AK, et al.: Fluoxetine in depressed patients on dialysis. Int J Psychiatry Med 27: 71–80, 1997
5. Friedli K, Guirguis A, Almond M, Day C, Chilcot J, Da Silva-Gane M, et al.: Sertraline versus placebo in patients with major depressive disorder undergoing hemodialysis: A randomized, controlled feasibility trial. Clin J Am Soc Nephrol 12: 280–286, 2017
6. Hedayati SS, Gregg LP, Carmody T, Jain N, Toups M, Rush AJ, et al.: Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: The CAST randomized clinical trial. JAMA 318: 1876–1890, 2017
7. Chilcot J, Hudson JL: Is successful treatment of depression in dialysis patients an achievable goal? Semin Dial 32: 210–214, 2018
8. Mehrotra R, Cukor D, Unruh M, Rue T, Heagerty P, Cohen SD, et al.: Comparative efficacy of therapies for treatment of depression for patients undergoing maintenance hemodialysis: A randomized clinical trial. Ann Intern Med 170: 369–379, 2019
9. Horowitz MA, Taylor D: Tapering of SSRI treatment to mitigate withdrawal symptoms [published online ahead of print March 5, 2019]. Lancet Psychiatry doi:10.1016/S2215-0366(19)30032-X