TY - JOUR

T1 - Serious arrhythmia in initiators of citalopram, escitalopram, and other selective serotonin reuptake inhibitors

T2 - A population-based cohort study in older adults

AU - Aakjær, Mia

AU - Werther, Sarah Kimmer

AU - De Bruin, Marie Louise

AU - Andersen, Morten

N1 - Funding Information: At the time of the study, M.L.D.B. was an employee of the Copenhagen Centre for Regulatory Science (CORS). CORS is a cross‐faculty university‐anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private (Novo Nordisk A/S, Lundbeck A/S, Ferring pharmaceuticals A/S, LEO pharma A/S) stakeholders as well as patient organizations (Rare Diseases Denmark). The center is purely devoted to the scientific aspects of the regulatory field and has a patient‐oriented focus, and the research is not a company‐specific product or directly company related. Currently, M.L.D.B. is employed by Utrecht University to conduct research under the umbrella of the Utrecht Centre for Pharmaceutical Policy and Regulation. This center receives no direct funding or donations from private parties, including the pharma industry. Research funding from public–private partnerships (e.g., IMI, The Escher Project; http://escher.lygature.org/), is accepted under the condition that no company‐specific study is conducted. The center has received unrestricted research funding from public sources (e.g., World Health Organization, Netherlands Organization for Health Research and Development, the Dutch National Health Care Institute, EC Horizon 2020, the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health). M.An. has participated in research projects funded by AstraZeneca, H. Lundbeck & Mertz, Novartis, and Pfizer, and has received fees for leading courses and teaching from Atrium, the Danish Association of the Pharmaceutical Industry. All other authors declared no competing interests for this work. Funding Information: The Pharmacovigilance Research Center is supported by a grant from the Novo Nordisk Foundation (NNF15SA0018404) to the University of Copenhagen. This includes the professorship of M.An. and part of the PhD study of M.Aa.

PY - 2022

Y1 - 2022

N2 - The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are associated with QT prolongation, which increases the risk of serious arrhythmia. Consequently, regulatory agencies issued safety warnings in 2011. This study aimed to investigate the risk of serious arrhythmia following initiation of citalopram or escitalopram compared to other SSRIs and the risk in the periods before and after the warnings were issued. We conducted a series of nationwide cohort studies emulating a target trial using Danish healthcare register data from January 1, 2002, to December 31, 2016. We included patients (aged ≥65 years) who filled an SSRI prescription with a 1-year washout period before the index date. The outcome was an event of serious arrhythmia. Individuals were followed for a maximum of 6 months using an intention-to-treat approach. Log-binomial regression analyses were performed, estimating risk ratios (RRs) and 95% confidence intervals (CIs) adjusting for age and sex, comorbidities, and comedications with propensity scores. Dose–response effects were not investigated because dosage instructions were not available. We included 167,366 (146,014 individuals), 40,113 (37,069 individuals), and 50,281 (44,754 individuals) person-trials of citalopram, escitalopram, and other SSRIs, respectively. In total, there were 228 events of serious arrhythmia. No difference in risk was observed in the entire study period for either citalopram (0.87 [0.62–1.22]) or escitalopram (0.85 [0.53–1.40]). We identified lower point estimates after the safety warning, RR 0.54 (95% CI 0.31–0.93) for citalopram and 0.58 (0.20–1.63) for escitalopram. Initiation of citalopram and escitalopram was not associated with an increased risk of serious arrhythmia. However, lower point estimates were observed after the safety warning.

AB - The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are associated with QT prolongation, which increases the risk of serious arrhythmia. Consequently, regulatory agencies issued safety warnings in 2011. This study aimed to investigate the risk of serious arrhythmia following initiation of citalopram or escitalopram compared to other SSRIs and the risk in the periods before and after the warnings were issued. We conducted a series of nationwide cohort studies emulating a target trial using Danish healthcare register data from January 1, 2002, to December 31, 2016. We included patients (aged ≥65 years) who filled an SSRI prescription with a 1-year washout period before the index date. The outcome was an event of serious arrhythmia. Individuals were followed for a maximum of 6 months using an intention-to-treat approach. Log-binomial regression analyses were performed, estimating risk ratios (RRs) and 95% confidence intervals (CIs) adjusting for age and sex, comorbidities, and comedications with propensity scores. Dose–response effects were not investigated because dosage instructions were not available. We included 167,366 (146,014 individuals), 40,113 (37,069 individuals), and 50,281 (44,754 individuals) person-trials of citalopram, escitalopram, and other SSRIs, respectively. In total, there were 228 events of serious arrhythmia. No difference in risk was observed in the entire study period for either citalopram (0.87 [0.62–1.22]) or escitalopram (0.85 [0.53–1.40]). We identified lower point estimates after the safety warning, RR 0.54 (95% CI 0.31–0.93) for citalopram and 0.58 (0.20–1.63) for escitalopram. Initiation of citalopram and escitalopram was not associated with an increased risk of serious arrhythmia. However, lower point estimates were observed after the safety warning.

U2 - 10.1111/cts.13319

DO - 10.1111/cts.13319

M3 - Journal article

C2 - 35733364

AN - SCOPUS:85132415235

VL - 15

SP - 2105

EP - 2115

JO - Clinical and Translational Science (Print)

JF - Clinical and Translational Science (Print)

SN - 1752-8054

IS - 9

ER -