Journal Article Annotations
2022, 2nd Quarter

Pyschonephrology

Annotations by Sahil Munjal, MD
July, 2022

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

PUBLICATION #1 — Pyschonephrology

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

Magdalene M Assimon, Patrick H Pun, Sana M Al-Khatib, M Alan Brookhart, Bradley N Gaynes, Wolfgang C Winkelmayer, Jennifer E Flythe

Abstract: 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.

Annotation

The finding:
In this retrospective cohort study analysing a national database, authors report an increased risk of sudden cardiac death (SCD) in haemodialysis patients on citalopram/escitalopram with concurrent PPI (Proton Pump Inhibitor) use. Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the highest risk of SCD (weighted HR [95% CI] = 1.31 [1.11–1.54]), followed by citalopram/escitalopram initiators not using a PPI (1.22 [1.06–1.41]). Sertraline initiators using versus not using a PPI had similar risks of SCD (1.03 [0.85–1.26]).

Strength and weaknesses:
Secondary outcomes as well as several sensitivity analyses showed consistent results. Residual confounding may remain, and there is a risk of misclassifying PPI exposure because various PPIs are available over the counter.

Relevance:
patients. This study highlights the pharmacokinetic and pharmacodynamic drug interactions of citalopram/escitalopram with concurrent PPIs in haemodialysis patients. PPIs are competitive inhibitors of the cytochrome P450 2C19 isoenzyme and can increase citalopram/escitalopram levels 50% to 120%. PPIs can also induce hypomagnesemia which can prolong the QT. In these patients, authors suggest conducting a baseline EKG prior to medication initiation and monitoring every 3 to 6 months. Sertraline may be a safer choice in such situations.

Type of study:
Cohort study