Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis

Abstract

Background Individuals receiving maintenance hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascular disease burden and high level of polypharmacy, as well as recurrent exposure to electrolyte shifts during dialysis. Electrophysiologic data indicate that among the selective serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. However, the relative cardiac safety of SSRIs in the hemodialysis population is unknown. Methods In this retrospective cohort study, we used data from a cohort of Medicare beneficiaries receiving hemodialysis included in the US Renal Data System registry (2007-2014). We used a new-user design to compare the 1-year risk of sudden cardiac death among hemodialysis patients initiating SSRIs with a higher potential for prolonging the QT interval (citalopram, escitalopram) versus the risk among those initiating SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, sertraline). We estimated adjusted hazard ratios using inverse probability of treatment weighted survival models. Nonsudden cardiac death was treated as a competing event. Results The study included 30,932 (47.1%) hemodialysis patients who initiated SSRIs with higher QTprolonging potential and 34,722 (52.9%) who initiated SSRIs with lower QT-prolonging potential. Initiation of an SSRI with higher versus lower QT-prolonging potential was associated with higher risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31). This association was more pronounced among elderly individuals, females, patients with conduction disorders, and those treated with other non-SSRI QT-prolonging medications. Conclusions The heterogeneous QT-prolonging potential of SSRIs may differentially affect cardiac outcomes in the hemodialysis population.

Antidepressant Usage in Haemodialysis Patients: Evidence of Sub‐Optimal Practice Patterns

“…CKD is also associated with accelerated heart disease (Bansal 2017) and many antidepressants are potentially cardiotoxic (Assimon et al . 2019). Polypharmacy is rife in patients with CKD, especially those on dialysis.…”

“…Furthermore, there is an increased mortality risk in HD patients on those SSRIs with a higher propensity to increase the electrocardiograph QT interval compared with those with lesser propensity (Assimon et al . 2019), though whether use of antidepressants is associated with an increased risk over that associated with depression itself, is not known.…”

Authors’ Reply

“…We thank Chilcot and Farrington 1 for their interest in our paper 2 and thoughtful comments surrounding the treatment of depression in hemodialysis patients. We agree with the letter writers that our observational study was not designed to evaluate the effect of antidepressant pharmacotherapy (versus no treatment) on mortality among individuals with hemodialysis-dependent ESRD.…”

“…Under our active comparator new-user design, we could only conclude that the initiation of a higher (citalopram and escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, and sertraline) QTprolonging potential selective serotonin reuptake inhibitor (SSRI) was associated with a higher risk of sudden cardiac death. 2 Our study was designed to reflect a clinician's decision to prescribe an SSRI with higher versus lower QT-prolonging potential to a hemodialysis patient (i.e., a treatment choice encountered in real-world practice). [2][3][4] The study provides population-specific safety information that clinicians can consider when prescribing SSRI therapy to hemodialysis patients.…”

“…2 Our study was designed to reflect a clinician's decision to prescribe an SSRI with higher versus lower QT-prolonging potential to a hemodialysis patient (i.e., a treatment choice encountered in real-world practice). [2][3][4] The study provides population-specific safety information that clinicians can consider when prescribing SSRI therapy to hemodialysis patients.…”