© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).Peer reviewe

Chilcot, Joseph

Farrington, Ken

Clinical Kidney Journal

English

University of Hertfordshire Research Archive

L E T T E R T O T H E E D I T O RSelf-reported antidepressant use in haemodialysispatients is associated with increased mortalityindependent of concurrent depression severityJoseph Chilcot1 and Ken Farrington2,31Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London,London, UK, 2Renal Unit, Lister Hospital, Stevenage, UK and 3Centre for Health Services and Clinical Research,University of Hertfordshire, Hatfield, UKCorrespondence to: Joseph Chilcot; E-mail: joseph.chilcot@kcl.ac.uk; Twitter handle: @joe_chilcotWe have recently argued the case for empirical studies evaluat-ing the selective withdrawal of antidepressants in patients withadvanced kidney disease [1]. This was in response to a large ret-rospective analysis that found that haemodialysis patients whoinitiated selective serotonin reuptake inhibitors (SSRIs) withhigher QT-prolonging potential (citalopram and escitalopram)had a significantly increased risk of sudden cardiac death {ad-justed hazard ratio [HR] 1.18 [95% confidence interval (CI) 1.05–1.31]} compared with patients who initiated SSRIs with lowerQT-prolonging potential (fluoxetine, fluvoxamine, paroxetineand sertraline) [2]. Furthermore, we highlighted three random-ized placebo-controlled trials of SSRIs in individuals with kidneydisease [3–5] that failed to show evidence of efficacy but indi-cated increased risks of adverse events. We concluded an exis-tent possibility that in some kidney patients, antidepressantsmay be doing more harm than good, therefore consideration ofwithdrawing antidepressants in suitable patients may be appro-priate. A recent review of the evidence base for antidepressantsin the general population reports minimal benefit to the averagepatient with major depressive disorder and concludes‘Antidepressants should not be used for adults with major de-pressive disorder before valid evidence has shown that the po-tential beneficial effects outweigh the harmful effects’ [6].Evidence regarding the association between depressionsymptoms and survival in dialysis patients is unequivocal [7–9].However, what is less clear is the role antidepressants have onsurvival and whether any effect is independent of depressionseverity. Assimon et al.’s [2] analysis, while compelling, does notprovide the mortality risk of being on an antidepressant versusnot. We therefore went back to reanalyse survival data pub-lished previously [7] in order to explore the association betweenantidepressant use and survival from a large sample of haemo-dialysis patients (n¼ 707) in which there were 148 deaths. Ouroriginal analyses demonstrated that depression severity pre-dicted all-cause mortality after controlling for a variety of cova-riates [Beck Depression Inventory-II, HR 1.03 (95% CI 1.01–1.04);Patient Health Questionnaire-9 (PHQ-9), HR 1.04 (95% CI 1.01–1.06)]. Using the same analytical methodology and modeladjustments, we reran the analyses including antidepressantuse within 3 months prior to the study assessment. Seventy-sixpatients reported being on at least one antidepressant (six miss-ing cases). Of those on antidepressants, 36% died during thestudy follow-up compared with 19% of patients not on an anti-depressant. In adjusted analysis that also controlled for depres-sion severity (PHQ-9), antidepressant use was significantlyassociated with mortality, increasing the hazard of death 2-fold[adjusted HR 2.0 (95% CI 1.28–3.26); P¼ 0.003; see Figure 1 for sur-vival plot]. Our previously reported findings from the originalanalysis remained the same, including the significance and ef-fect size of depression severity on mortality. This suggests thatthe association between antidepressant use and mortality inhaemodialysis patients may well be independent of concurrentdepression severity. The estimated absolute risk increase ofdeath for those on an antidepressant was 18%, with a numbersneeded to harm of 5.Received: 9.10.2019; Editorial decision: 14.10.2019VC The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.For commercial re-use, please contact journals.permissions@oup.com1109Clinical Kidney Journal, 2020, vol. 13, no. 6, 1109–1110doi: 10.1093/ckj/sfz160Advance Access Publication Date: 14 November 2019Letter to the EditorDownloaded from https://academic.oup.com/ckj/article/13/6/1109/5625688 by guest on 23 April 2021This exploratory reanalysis is limited by patient self-reported antidepressant use. We did not have data on medica-tion type or regimen, dose or treatment vintage. Accordingly,more robust studies are needed to ascertain more reliable esti-mates from which to establish the absolute mortality risk in-crease of antidepressants in this setting. Nevertheless, we feel itis important to report this exploratory observation, which in ouropinion further supports the call for empirical studies investi-gating the selective withdrawal of antidepressants in patientswith advanced kidney disease.FUNDINGThis article presents independent research funded by theNational Institute for Health Research (NIHR) under itsResearch for Patient Benefit Programme (grant referencenumber PB-PG-1112-29078). The views expressed are thoseof the authors and not necessarily those of the NationalHealth Service, the NIHR or the Department of Health.CONFLICT OF INTEREST STATEMENTNone declared.REFERENCES1. Chilcot J, Farrington K. The case for selective withdrawal ofantidepressants in patients with advanced kidney disease.J Am Soc Nephrol 2019; 30: 1339–13402. Assimon MM, Brookhart MA, Flythe JE. Comparative cardiacsafety of selective serotonin reuptake inhibitors among indi-viduals receiving maintenance hemodialysis. J Am Soc Nephrol2019; 30: 611–6233. Blumenfield M, Levy NB, Spinowitz B et al. Fluoxetine in de-pressed patients on dialysis. Int J Psychiatry Med 1997; 27:71–804. Friedli K, Guirguis A, Almond M et al. Sertraline versus placeboin patients with major depressive disorder and undergoinghaemodialysis (ASSertID): a randomised, controlled feasibil-ity trial. Clin J Am Soc Nephrol 2017; 12: 280–2865. Hedayati SS, Gregg LP, Carmody T et al. Effect of sertraline ondepressive symptoms in patients with chronic kidney diseasewithout dialysis dependence the CAST randomized clinicaltrial. J Am Med Assoc 2017; 318: 1876–18906. Jakobsen JC, Gluud C, Kirsch I. Should antidepressants beused for major depressive disorder? BMJ Evidence Based Med2019; doi: 10.1136/bmjebm-2019-1112387. Chilcot J, Guirguis A, Friedli K et al. Depression symptoms inhaemodialysis patients predict all-cause mortality but notkidney transplantation: a cause-specific outcome analysis.Ann Behav Med 2018; 52: 1–88. Chilcot J, Davenport A, Wellsted D et al. An association be-tween depressive symptoms and survival in incident dialysispatients. Nephrol Dial Transplant 2011; 26: 1628–16349. Farrokhi F, Abedi N, Beyene J et al. Association between de-pression and mortality in patients receiving long-term dialy-sis: a systematic review and meta-analysis. Am J Kidney Dis2014; 63: 623–635P = 0.003FIGURE 1: Adjusted survival plot comparing patients using an antidepressant in the previous 3 months prior to study assessment versus nouse.1110 | J. Chilcot and K. FarringtonDownloaded from https://academic.oup.com/ckj/article/13/6/1109/5625688 by guest on 23 April 2021

Self-reported antidepressant use in haemodialysis patients is associated with increased mortality independent of concurrent depression severity

King's Research Portal

                       King’s Research Portal  DOI:10.1093/CKJ/SFZ160Document VersionPublisher's PDF, also known as Version of recordLink to publication record in King's Research PortalCitation for published version (APA):Chilcot, J., & Farrington, K. (2020). Self-reported anti-depressant use in haemodialysis patients is associatedwith increased mortality, independently of concurrent depression severity. Clinical Kidney Journal, 13(6), 1109-1110. https://doi.org/10.1093/CKJ/SFZ160Citing this paperPlease note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this maydiffer from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination,volume/issue, and date of publication details. 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Oct. 2023L E T T E R T O T H E E D I T O RSelf-reported antidepressant use in haemodialysispatients is associated with increased mortalityindependent of concurrent depression severityJoseph Chilcot1 and Ken Farrington2,31Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London,London, UK, 2Renal Unit, Lister Hospital, Stevenage, UK and 3Centre for Health Services and Clinical Research,University of Hertfordshire, Hatfield, UKCorrespondence to: Joseph Chilcot; E-mail: joseph.chilcot@kcl.ac.uk; Twitter handle: @joe_chilcotWe have recently argued the case for empirical studies evaluat-ing the selective withdrawal of antidepressants in patients withadvanced kidney disease [1]. This was in response to a large ret-rospective analysis that found that haemodialysis patients whoinitiated selective serotonin reuptake inhibitors (SSRIs) withhigher QT-prolonging potential (citalopram and escitalopram)had a significantly increased risk of sudden cardiac death {ad-justed hazard ratio [HR] 1.18 [95% confidence interval (CI) 1.05–1.31]} compared with patients who initiated SSRIs with lowerQT-prolonging potential (fluoxetine, fluvoxamine, paroxetineand sertraline) [2]. Furthermore, we highlighted three random-ized placebo-controlled trials of SSRIs in individuals with kidneydisease [3–5] that failed to show evidence of efficacy but indi-cated increased risks of adverse events. We concluded an exis-tent possibility that in some kidney patients, antidepressantsmay be doing more harm than good, therefore consideration ofwithdrawing antidepressants in suitable patients may be appro-priate. A recent review of the evidence base for antidepressantsin the general population reports minimal benefit to the averagepatient with major depressive disorder and concludes‘Antidepressants should not be used for adults with major de-pressive disorder before valid evidence has shown that the po-tential beneficial effects outweigh the harmful effects’ [6].Evidence regarding the association between depressionsymptoms and survival in dialysis patients is unequivocal [7–9].However, what is less clear is the role antidepressants have onsurvival and whether any effect is independent of depressionseverity. Assimon et al.’s [2] analysis, while compelling, does notprovide the mortality risk of being on an antidepressant versusnot. We therefore went back to reanalyse survival data pub-lished previously [7] in order to explore the association betweenantidepressant use and survival from a large sample of haemo-dialysis patients (n¼ 707) in which there were 148 deaths. Ouroriginal analyses demonstrated that depression severity pre-dicted all-cause mortality after controlling for a variety of cova-riates [Beck Depression Inventory-II, HR 1.03 (95% CI 1.01–1.04);Patient Health Questionnaire-9 (PHQ-9), HR 1.04 (95% CI 1.01–1.06)]. Using the same analytical methodology and modeladjustments, we reran the analyses including antidepressantuse within 3 months prior to the study assessment. Seventy-sixpatients reported being on at least one antidepressant (six miss-ing cases). Of those on antidepressants, 36% died during thestudy follow-up compared with 19% of patients not on an anti-depressant. In adjusted analysis that also controlled for depres-sion severity (PHQ-9), antidepressant use was significantlyassociated with mortality, increasing the hazard of death 2-fold[adjusted HR 2.0 (95% CI 1.28–3.26); P¼ 0.003; see Figure 1 for sur-vival plot]. Our previously reported findings from the originalanalysis remained the same, including the significance and ef-fect size of depression severity on mortality. This suggests thatthe association between antidepressant use and mortality inhaemodialysis patients may well be independent of concurrentdepression severity. The estimated absolute risk increase ofdeath for those on an antidepressant was 18%, with a numbersneeded to harm of 5.Received: 9.10.2019; Editorial decision: 14.10.2019VC The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.For commercial re-use, please contact journals.permissions@oup.com1Clinical Kidney Journal, 2019, 1–2doi: 10.1093/ckj/sfz160Letter to the EditorDownloaded from https://academic.oup.com/ckj/advance-article-abstract/doi/10.1093/ckj/sfz160/5625688 by guest on 15 November 2019This exploratory reanalysis is limited by patient self-reported antidepressant use. We did not have data on medica-tion type or regimen, dose or treatment vintage. Accordingly,more robust studies are needed to ascertain more reliable esti-mates from which to establish the absolute mortality risk in-crease of antidepressants in this setting. Nevertheless, we feel itis important to report this exploratory observation, which in ouropinion further supports the call for empirical studies investi-gating the selective withdrawal of antidepressants in patientswith advanced kidney disease.FUNDINGThis article presents independent research funded by theNational Institute for Health Research (NIHR) under itsResearch for Patient Benefit Programme (grant referencenumber PB-PG-1112-29078). The views expressed are thoseof the authors and not necessarily those of the NationalHealth Service, the NIHR or the Department of Health.CONFLICT OF INTEREST STATEMENTNone declared.REFERENCES1. Chilcot J, Farrington K. The case for selective withdrawal ofantidepressants in patients with advanced kidney disease.J Am Soc Nephrol 2019; 30: 1339–13402. Assimon MM, Brookhart MA, Flythe JE. Comparative cardiacsafety of selective serotonin reuptake inhibitors among indi-viduals receiving maintenance hemodialysis. J Am Soc Nephrol2019; 30: 611–6233. Blumenfield M, Levy NB, Spinowitz B et al. Fluoxetine in de-pressed patients on dialysis. Int J Psychiatry Med 1997; 27:71–804. Friedli K, Guirguis A, Almond M et al. Sertraline versus placeboin patients with major depressive disorder and undergoinghaemodialysis (ASSertID): a randomised, controlled feasibil-ity trial. Clin J Am Soc Nephrol 2017; 12: 280–2865. Hedayati SS, Gregg LP, Carmody T et al. Effect of sertraline ondepressive symptoms in patients with chronic kidney diseasewithout dialysis dependence the CAST randomized clinicaltrial. J Am Med Assoc 2017; 318: 1876–18906. Jakobsen JC, Gluud C, Kirsch I. Should antidepressants beused for major depressive disorder? BMJ Evidence Based Med2019; doi: 10.1136/bmjebm-2019-1112387. Chilcot J, Guirguis A, Friedli K et al. Depression symptoms inhaemodialysis patients predict all-cause mortality but notkidney transplantation: a cause-specific outcome analysis.Ann Behav Med 2018; 52: 1–88. Chilcot J, Davenport A, Wellsted D et al. An association be-tween depressive symptoms and survival in incident dialysispatients. Nephrol Dial Transplant 2011; 26: 1628–16349. Farrokhi F, Abedi N, Beyene J et al. Association between de-pression and mortality in patients receiving long-term dialy-sis: a systematic review and meta-analysis. Am J Kidney Dis2014; 63: 623–635P = 0.003FIGURE 1: Adjusted survival plot comparing patients using an antidepressant in the previous 3 months prior to study assessment versus nouse.2 | J. Chilcot and K. FarringtonDownloaded from https://academic.oup.com/ckj/advance-article-abstract/doi/10.1093/ckj/sfz160/5625688 by guest on 15 November 2019

Self-reported anti-depressant use in haemodialysis patients is associated with increased mortality, independently of concurrent depression severity

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Self-reported antidepressant use in haemodialysis patients is associated with increased mortality independent of concurrent depression severity

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