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TY - JOUR

T1 - Risk of out-of-hospital cardiac arrest in antidepressant drug users

AU - Eroglu, Talip E.

AU - Barcella, Carlo A.

AU - Gerds, Thomas A.

AU - Kessing, Lars Vedel

AU - Zylyftari, Nertila

AU - Mohr, Grimur H.

AU - Kragholm, Kristian

AU - Polcwiartek, Christoffer

AU - Wissenberg, Mads

AU - Folke, Fredrik

AU - Tan, Hanno L.

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H.

N1 - Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation programme under the acronym ESCAPE‐NET, registered under grant agreement No 733381 (T.E.E., H.L.T.), and the COST Action PARQ (grant agreement No CA19137) supported by COST (European Cooperation in Science and Technology). The funders were not involved in designing the study, collecting and analysing the data, preparing the manuscript, or decision to publish. The funders were not involved in designing the study, collecting and analysing the data, preparing the manuscript, or decision to publish. Funding Information: L.V.K has for 3 years been a consultant for Lundbeck and Teva. N.Z. has received funding from the European Union's Horizon 2020 research and innovation program ESCAPE‐NET and Helsefonden. All other authors have no interests to declare. Publisher Copyright: © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

KW - antidepressants

KW - depolarization-blocking drugs

KW - sudden cardiac arrest

UR - http://www.scopus.com/inward/record.url?scp=85124572589&partnerID=8YFLogxK

U2 - 10.1111/bcp.15224

DO - 10.1111/bcp.15224

M3 - Article

C2 - 35001414

VL - 88

SP - 3162

EP - 3171

JO - British journal of clinical pharmacology

JF - British journal of clinical pharmacology

SN - 0306-5251

IS - 7

ER -