Risk of out‐of‐hospital cardiac arrest in antidepressant drug users

Abstract

Conflicting results have been reported regarding the association between antidepressant use and out‐of‐hospital cardiac arrest (OHCA) risk. We investigated whether the use of antidepressants is associated with OHCA. Methods We conducted a nationwide nested case–control study to assess the association of individual antidepressant drugs within drug classes with the hazard of OHCA. Cases were defined as OHCA from presumed cardiac causes. Cox regression with time‐dependent exposure and time‐dependent covariates was conducted to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) overall and in subgroups defined by established cardiac disease and cardiovascular risk factors. Also, we studied antidepressants with and without sodium channel blocking or potassium channel blocking properties separately. Results During the study period from 2001 to 2015 we observed 10 987 OHCA cases, and found increased OHCA rate for high‐dose citalopram (>20 mg) and high‐dose escitalopram (>10 mg; HR:1.46 [95% CI:1.27–1.69], HR:1.43 [95% CI:1.16–1.75], respectively) among selective serotonin reuptake inhibitors (reference drug sertraline), and for high‐dose mirtazapine (>30; HR:1.59 [95% CI:1.18–2.14]) among the serotonin–norepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine). Among tricyclic antidepressants (reference drug amitriptyline), no drug was associated with significantly increased OHCA rate. Increased OHCA rate was found for antidepressants with known potassium channel blocking properties (HR:1.14 [95% CI:1.05–1.23]), but for not those with sodium channel blocking properties. Citalopram, although not statistically significant, and mirtazapine were associated with increased OHCA rate in patients without cardiac disease and cardiovascular risk factors. Conclusion Our findings indicate that careful titration of citalopram, escitalopram and mirtazapine dose may have to be considered due to drug safety issues.

Serious arrhythmia in initiators of citalopram, escitalopram, and other selective serotonin reuptake inhibitors: A population‐based cohort study in older adults

“…Qirjazi et al 21 conducted a cohort study from 2002 to 2012 examining the risk of arrhythmia among older adults (≥65) newly prescribed citalopram and escitalopram, compared to sertraline and paroxetine. A recent nested case–control study from Denmark using data from the Danish Cardiac Arrest Registry found higher rates of out‐of‐hospital cardiac arrest among users of high‐dose citalopram (>20 mg) and escitalopram (>10 mg) compared to users of sertraline 22 …”

“…A recent nested case-control study from Denmark using data from the Danish Cardiac Arrest Registry found higher rates of out-of-hospital cardiac arrest among users of high-dose citalopram (>20 mg) and escitalopram (>10 mg) compared to users of sertraline. 22 Our study differs from the existing studies by emulating a target trial in which individuals can be eligible for inclusion multiple times. Moreover, two of the previous studies did not include older adults in their cohorts, 14,16 whereas three included both younger and older adults.…”

“…Conflicting evidence has arisen from observational studies in which the majority have not identified increased risks 14–19 . However, three studies did 20–22 . The first study was published in 2011 by Weeke et al It was a nationwide Danish case‐time‐control study that examined the risk of cardiac arrest associated with episodes of use of each SSRI compared to episodes of no use 20 .…”

“…In a Canadian cohort study from 2016, Qirjazi et al identified a small increased risk of ventricular arrhythmia among users of citalopram compared to users of paroxetine and sertraline 21 . Recently, a Danish case–control study found higher rates of out‐of‐hospital cardiac arrest among high‐dose citalopram users (>20 mg) and high‐dose escitalopram users (>10 mg) compared to users of sertraline 22 . To our knowledge, no study has identified an increased risk of serious arrhythmia following initiation of escitalopram compared to other SSRIs.…”

“… 14 , 15 , 16 , 17 , 18 , 19 However, three studies did. 20 , 21 , 22 The first study was published in 2011 by Weeke et al It was a nationwide Danish case‐time‐control study that examined the risk of cardiac arrest associated with episodes of use of each SSRI compared to episodes of no use. 20 In a Canadian cohort study from 2016, Qirjazi et al identified a small increased risk of ventricular arrhythmia among users of citalopram compared to users of paroxetine and sertraline.…”