Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis

Pharmacoepidemiol Drug Saf. 2022 Jun;31(6):670-679. doi: 10.1002/pds.5428. Epub 2022 Mar 24.


Purpose: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug-drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT-prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions.

Methods: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007-2017) and a new-user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1-year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11-1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06-1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85-1.26]).

Conclusions: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients.

Keywords: USRDS; citalopram; escitalopram; hemodialysis; proton pump inhibitor; sudden cardiac death.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Citalopram* / adverse effects
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology
  • Escitalopram
  • Humans
  • Proton Pump Inhibitors / adverse effects
  • Renal Dialysis
  • Retrospective Studies
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Sertraline* / adverse effects


  • Antidepressive Agents
  • Proton Pump Inhibitors
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Escitalopram
  • Sertraline